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Jacqueline Vock, Universitätsklinik für Radio-Onkologie, Inselspital SRO Tutorial Palliative Care 04.05.2012 Palliative Radiotherapy

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Page 1: SRO Tutorial Palliative Care 04.05.2012 Palliative Radiotherapy · 2018-02-22 · SRO Tutorial Palliative Care – Palliative Radiotherapy 30 Jacqueline Vock, Universitätsklinik

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie Inselspital

SRO Tutorial Palliative Care

04052012

Palliative Radiotherapy

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 2

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Many thanks tohellip

bull Introduction Palliative Care

ndashKamilla Kruumlger

ndashDr Steffen Eychmuumlller Palliative care unit

bull Introduction Pain therapy

ndashPD Konrad Streitberger Pain service

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 3

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Importance of palliative radiotherapy in a radiation

oncology department

bull Importance of (palliative) radiotherapy in the treatment of

cancer patients

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 4

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Radiotherapy 50 of patients

Palliative

25

curative

26

Courtesy of D Aebersold

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 5

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brainstorming

bull Differences between curative and palliative radiotherapy

bull What aspects have to be considered

bull Aimsindications of palliative radiotherapy

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 6

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Aims

ndashReduction of existing symptoms

ndashPrevention of immanent symptoms

bull Important

bull Consider

ndashPerformance status

ndashLife expectancy

ndashToxicity

ndashDuration of palliation

bull Quality of life What is important for the patient

bull Not too long (hypofractionation) little toxicity

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 7

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Pain

ndashBone

ndashSoft tissue

bull Neurologic compression

ndashSpinal cord

ndashPeripheral nerves

ndashBrain

bull Haemorrhage

bull Symptoms caused by obstruction

ndashAirways dyspnoea

ndashSwallowing route dysphagia

ndashVenous flow superiorinferior cava syndrome

ndashUrinary tract urinary retention renal failure

bull Cosmesis odour in tumours infiltrating the skin

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 8

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz Cancer J 2010

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 9

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz Cancer J 2010

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 10

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Van Oorschot Sem Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 11

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 12

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cancer 2010

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 13

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastases

bull What tumours

bull Does RT work

bull Causal and symptomatic effect (anti-tumour anti-

inflammatory)

bull How do you treat them Why Studies on fractionation

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 14

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

RT of bone metastases -

fractionation

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 15

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lievens RO 2000

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 16

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lievens RO 2000

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 17

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Konski Semin Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 18

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Konski Semin Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 19

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Overall

response

rate

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 20

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Complete

response

rate

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 21

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Retreat

ment

rate

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 22

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull EBRT significant palliation of painful bone metastasis in

50-80 of patients complete pain relief in up to 13 of

patients (Chow JCO 2007)

bull Optimal fractionation RT technique combination with other

treatment options

bull Systematic review combined with expert opinions

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 23

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Uncomplicated bone

metastasis

Single vs multiple

fractions

bull Pain relief

equivalent

bull Long term toxicity

equivalent

bull Single fraction

optimal patient and

caregiver

convenience

bull Retreatment rate

20 vs 8

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 24

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Repeat treatment of painful spinal metastasis

bull Pain relief in 46-80

bull Cave dose to spinal cord

bull Dosefractionation unclear

bull Recommendation prospective trial

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 25

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Comparable fracture risk Chow Clin Oncol 2012

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 26

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Comparable risk of

spinal cord

compression

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 27

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SBRT of spinal metastasis

bull Mostly retrospective single-institution series

bull Recommendation prospective trial

bull Not primary treatment for spinal met causing spinal cord

compression

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 28

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Radionuclides

bull Important often underused option for multifocal bone

metastasis

bull For osteoblastic metastasis

bull Based on available data do not obviate need for EBRT

bull Recommendation prospective studies on prophylactic use

of radiopharmaceuticals in patients with limited bone

metastases combination with other systemic agents

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 29

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 30

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Biphosphonates

bull Several prospective studies on concurrent EBRT and

biphosphonates successful pain relief promotion of re-

ossification of damaged bone acceptable risk of toxicity

bull Not shown that combination better than EBRT alone for

pain relief

bull Recommendation prospective trial on optimum RT

fractionation EBRT versus radionuclides dose and

duration of biphosphonates and scheduling

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 31

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 32

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Denosumab

Lipton Curr Opp Supp Pall Care 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 33

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lipton Curr Opp Supp

Pall Care 2011

Denosumab versus

Zoledronate

Prevention of SREs (path fracture RT or OP to bone

spinal cord compression)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 34

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Breast

superior

Prostate

superior

Other solid

tumors or

multiple

myeloma

non inferior

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 35

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Vertebroplastykyphoplasty

bull No prospective data to suggest

that vertkyph obviates the

need for EBRT in painful bone

met

bull Small series of patients treated

by vertkyph plus EBRT

bull Recommendation prospective

trials on patient selection

efficacy toxicity and timing of

vertkyph and RT

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 36

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 37

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Non inferiority study

bull 272 patients randomized

Neuropathic pain

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 38

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 39

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 40

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Spinal cord compression

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 41

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 42

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 43

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Patchell Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 44

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

RT short versus

long course

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 45

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 46

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 47

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 48

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 49

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 50

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull SRO tutorial CNS PD Dr A Pica

bull ScocciantiRicardi Radiother Oncol 2012 Review

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 51

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemorrhage

bull Bleeding in 6-10 of patients with advanced

cancer (Pereira et al Topics in Palliative Care Vol 4 New York

Oxford University Press 2000)

bull haemoptysis

bull haematemesis

bull haematocheziamelaena

bull vaginal bleeding

bull haematuria

bull bleeding in ulcerated skin lesions

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 52

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Mechanisms of haemostatic radiotherapy

bull Sparse literature

bull Coagulation activationsup1

ndash Oxydative endothelial damage

ndash Activation of thrombocytes

ndash Activation of inflammation

bull Long term anti-angiogenetic

sup1 Hallahan et al Oncology (Huntingt) 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 53

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Prostate cancer

bull Reduction of pain and bleeding in hormone refractory

prostate cancer (Kynaston Br J Urol 1990 Kawakami Nippon

Hinyokika Gakkai Zasshi 1993 Kalapurakal Int J Radiat Oncol Biol Phys

2003)

bull 100 improvement in patients with important hematuria (Carlton J Urol 1972)

Bladder cancer (Srinivasan et al Clin Oncol (R Coll Radiol) 1994)

bull 17 Gy in 2 fractions3 days 59 clearance of hematuria

bull 45 Gy in 12 fractions26 days 16 clearance of

hematuria

bull Selection by performance status Palliation (pain and

hematuria) better with hypofractionated RT worse

survival

bull No important side effects

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 54

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung cancer

bull Control of hemoptysis in up to 80 of patients (Brundage

Can J Oncol 1996 Medical Research Council Lung Cancer Working Party

Br J Cancer 1992 Hoskin in Doyle et al Second Edition New York

Oxford University Press 1998 Langendijk Int J Radiat Oncol Biol Phys

2000)

bull Optimal dosefractionation

ndash Hypofractionated RT seems to be equally effective to multiple

fractions (Rees Clin Oncol (R Coll Radiol) 1997 Sundstrom JCO

2004 Phase III Stevens Australas Radiol 1995 Phase III studies of

the MRC (s above)

ndash 10 Gy Single fraction equally effective to multiple fractions less

toxic (Hoskin in Doyle et al Second Edition New York Oxford

University Press 1998 Medical Research Council Lung Cancer

Working Party Br J Cancer 1992)

ndash Mostly total dose of around 20 Gy (multiple fractions) or 8 Gy

single fraction recommended

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 55

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Van Lonkhuijzen

Radiother Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 56

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gynaecologic tumours

bull Cf review van Lonkhuijzen Radiother Oncol 2011

bull Consider intracavitary HDR brachytherapy

Rectal cancer

bull Up to 85 control of rectal bleeding (Hoskin in Doyle et al Second Edition New York Oxford University Press 1998)

Kaposi sarcoma

bull Good palliation for pain bleeding or edema TD 15-40 Gy SD 2 Gy gt90 response 70 complete remission (Review Becker et al Onkologie 2006)

Skin tumours (Miller in Doyle Oxford Textbook of Palliative Medicine New York Oxford University Press 1993)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 57

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duration of treatment effect

Lung cancer

bull Median duration of palliation 50 of remaining life span (30 Gy10d

27 Gy6d 17 Gy2 fract1w apart) (Medical Research Council Br J

Cancer 1991)

bull 1 fract 10 Gy vs 2 fract 85 Gy more patients need repeat RT (Medical Research Council Lung Cancer Working Party Br J Cancer 1992)

bull 417 pat need repeat RT within 3 m after 1x10 Gy (Scolaro Radiol

Med 1995)

Rec ovarian cancer

bull Median duration of palliation 4 m in 90 of patients until death (Corn Cancer 1994)

Cervical endometrial cancer

bull In 50 of patients pall Effect until death with 1-2x10 Gy

ndash Halle IJROBP 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 58

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull RT effective for improvement of

ndashThoracic symptoms (haemoptysis cough thoracic pain

dyspnoea airway obstruction) (Sirzeacuten Acta Oncol 2003 and others)

ndashQOL in about 13 of patients (Langendijk IJROBP 2000)

RT schedules

bull Systematic review (Fairchild JCO 264001-4011 2008)

ndash13 randomized trials 3473 patients

ndashdifferent RT schedules

ndashAim find optimal RT schedule for maximal palliation with

minimal toxicityneed for reirradiation

Thoracic symptoms

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 59

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz

Cancer

2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 60

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz Chow Hartsell Konski Cancer 2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 61

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemoptysis

bull Fig2 toux

733 689

812 802

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 62

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig3 doul thor 321 279

535 482

Cough

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 63

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 4 overall symptom burden

575 519

648 638

Thoracic pain

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 64

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 5 survie 1a

Cutoff (sensitivity analysis) BED[10] 35Gy vs LD

100 162

555 609

Overall symptom burden

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 65

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cutoff BED[10] 35Gy vs LD

265 217

Overall survival at 1y

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 66

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 7 Tox dysphagie

Cutoff BED[10] 30Gy vs LD

205 149

about x 2

Toxicity (dysphagia)

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 67

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomized trial 250 patients (Falk BMJ 2002)

bull Locally advanced non resectable NSCLC with minimal thoracic symptoms

bull Immediate vs delayed RT (at symptom onset)

bull In delayed arm 56 of patients died without RT

bull No difference in QOL odr OS

bull More acute toxicity in immediate RT arm

Randomized trial (Sundstrom Radiother Oncol 2005)

bull Advanced NSCLC

bull 2 RT schedules (5x4Gy vs 2x85 Gy) immediate RT

bull Stratification according to presenceabsence of thoracic symptoms

bull In asymptomatic patients no long term symptom control but important dysphagia

Timing

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 68

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull in 97 malignant

bull in 5-10 of lung cancer patients

bull Histology (exclude benign disease RT-chemosensible tumours

bull Generally spontanous improvement of symptoms by formation of collaterals

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 69

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Treatment

1 symptomatic

bull steroids

bull diuretics

bull Elevation of headthorax

2 causal bull chemotherapy (SCLC

lymphomas germinal tumours)

bull Endovascular stent placement

bull radiotherapy Palliative care in lung cancer ACCP

evidence- based clinical practice guidelines

(2nd edition)

Kvale Chest 2007

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 70

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

Radiotherapy

bull Mostly clinical response within 72 h

bull Complete clinical response at 2 w in 78 of patients with SCLC

and 63 of patients with NSCLC

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 71

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 72

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 73

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duhamel Atlas clinique des maladies

des voies aeacuteriennes Elsevier

wwwupmccancercenterscom

Endobronchial brachytherapy

Cochrane analysis (Cardona The Cochrane

Library 2008)

bull No improved

symptom relief by

addition of

endobronchial

brachytherapy to

EBRT

bull Indicated in selected

patients pretreated

by EBRT with

central

endobronchial

obstruction

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 74

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Ozkok Lung Cancer 2008

Endobronchial brachytherapy

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 75

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Take home lung cancer

Dosefractionation

bull Minimum 10x3 Gy 5xw or equivalent

ndash better symptom control and better overall survival

ndash But more toxicity

bull Short schedule for symptom control and limited toxicity

ndashPoor performance status limited life expectancy

Timing

bull RT at the moment of symptom onset

bull No place for bdquoprophylactic palliative RTldquo according to evidence based guidelines

ndashExceptions

bull Young patient good PS aim of local control

bull Imminent symptoms (superior vena cava syndrome central airway obstruction

Rodrigues Pract Rad Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 76

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 77

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 78

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 80

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 81

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 82

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 83

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 84

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 85

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 90

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

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Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

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bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

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Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

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Scoccianti Radiother Oncol 2012

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Many thanks tohellip

bull Introduction Palliative Care

ndashKamilla Kruumlger

ndashDr Steffen Eychmuumlller Palliative care unit

bull Introduction Pain therapy

ndashPD Konrad Streitberger Pain service

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 3

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Importance of palliative radiotherapy in a radiation

oncology department

bull Importance of (palliative) radiotherapy in the treatment of

cancer patients

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 4

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Radiotherapy 50 of patients

Palliative

25

curative

26

Courtesy of D Aebersold

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 5

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brainstorming

bull Differences between curative and palliative radiotherapy

bull What aspects have to be considered

bull Aimsindications of palliative radiotherapy

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 6

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Aims

ndashReduction of existing symptoms

ndashPrevention of immanent symptoms

bull Important

bull Consider

ndashPerformance status

ndashLife expectancy

ndashToxicity

ndashDuration of palliation

bull Quality of life What is important for the patient

bull Not too long (hypofractionation) little toxicity

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 7

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Pain

ndashBone

ndashSoft tissue

bull Neurologic compression

ndashSpinal cord

ndashPeripheral nerves

ndashBrain

bull Haemorrhage

bull Symptoms caused by obstruction

ndashAirways dyspnoea

ndashSwallowing route dysphagia

ndashVenous flow superiorinferior cava syndrome

ndashUrinary tract urinary retention renal failure

bull Cosmesis odour in tumours infiltrating the skin

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 8

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz Cancer J 2010

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 9

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz Cancer J 2010

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 10

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Van Oorschot Sem Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 11

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 12

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cancer 2010

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 13

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastases

bull What tumours

bull Does RT work

bull Causal and symptomatic effect (anti-tumour anti-

inflammatory)

bull How do you treat them Why Studies on fractionation

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 14

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

RT of bone metastases -

fractionation

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 15

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Lievens RO 2000

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 16

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lievens RO 2000

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 17

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Konski Semin Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 18

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Konski Semin Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 19

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Overall

response

rate

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 20

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Complete

response

rate

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 21

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Retreat

ment

rate

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 22

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull EBRT significant palliation of painful bone metastasis in

50-80 of patients complete pain relief in up to 13 of

patients (Chow JCO 2007)

bull Optimal fractionation RT technique combination with other

treatment options

bull Systematic review combined with expert opinions

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 23

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Uncomplicated bone

metastasis

Single vs multiple

fractions

bull Pain relief

equivalent

bull Long term toxicity

equivalent

bull Single fraction

optimal patient and

caregiver

convenience

bull Retreatment rate

20 vs 8

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 24

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Repeat treatment of painful spinal metastasis

bull Pain relief in 46-80

bull Cave dose to spinal cord

bull Dosefractionation unclear

bull Recommendation prospective trial

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 25

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Comparable fracture risk Chow Clin Oncol 2012

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 26

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Comparable risk of

spinal cord

compression

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 27

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SBRT of spinal metastasis

bull Mostly retrospective single-institution series

bull Recommendation prospective trial

bull Not primary treatment for spinal met causing spinal cord

compression

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 28

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Radionuclides

bull Important often underused option for multifocal bone

metastasis

bull For osteoblastic metastasis

bull Based on available data do not obviate need for EBRT

bull Recommendation prospective studies on prophylactic use

of radiopharmaceuticals in patients with limited bone

metastases combination with other systemic agents

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 29

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 30

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Biphosphonates

bull Several prospective studies on concurrent EBRT and

biphosphonates successful pain relief promotion of re-

ossification of damaged bone acceptable risk of toxicity

bull Not shown that combination better than EBRT alone for

pain relief

bull Recommendation prospective trial on optimum RT

fractionation EBRT versus radionuclides dose and

duration of biphosphonates and scheduling

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 31

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 32

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Denosumab

Lipton Curr Opp Supp Pall Care 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 33

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lipton Curr Opp Supp

Pall Care 2011

Denosumab versus

Zoledronate

Prevention of SREs (path fracture RT or OP to bone

spinal cord compression)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 34

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Breast

superior

Prostate

superior

Other solid

tumors or

multiple

myeloma

non inferior

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 35

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Vertebroplastykyphoplasty

bull No prospective data to suggest

that vertkyph obviates the

need for EBRT in painful bone

met

bull Small series of patients treated

by vertkyph plus EBRT

bull Recommendation prospective

trials on patient selection

efficacy toxicity and timing of

vertkyph and RT

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 36

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 37

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Non inferiority study

bull 272 patients randomized

Neuropathic pain

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 38

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 39

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 40

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Spinal cord compression

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 41

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 42

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 43

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Patchell Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 44

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

RT short versus

long course

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 45

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 46

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 47

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 48

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 49

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 50

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull SRO tutorial CNS PD Dr A Pica

bull ScocciantiRicardi Radiother Oncol 2012 Review

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 51

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemorrhage

bull Bleeding in 6-10 of patients with advanced

cancer (Pereira et al Topics in Palliative Care Vol 4 New York

Oxford University Press 2000)

bull haemoptysis

bull haematemesis

bull haematocheziamelaena

bull vaginal bleeding

bull haematuria

bull bleeding in ulcerated skin lesions

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 52

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Mechanisms of haemostatic radiotherapy

bull Sparse literature

bull Coagulation activationsup1

ndash Oxydative endothelial damage

ndash Activation of thrombocytes

ndash Activation of inflammation

bull Long term anti-angiogenetic

sup1 Hallahan et al Oncology (Huntingt) 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 53

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Prostate cancer

bull Reduction of pain and bleeding in hormone refractory

prostate cancer (Kynaston Br J Urol 1990 Kawakami Nippon

Hinyokika Gakkai Zasshi 1993 Kalapurakal Int J Radiat Oncol Biol Phys

2003)

bull 100 improvement in patients with important hematuria (Carlton J Urol 1972)

Bladder cancer (Srinivasan et al Clin Oncol (R Coll Radiol) 1994)

bull 17 Gy in 2 fractions3 days 59 clearance of hematuria

bull 45 Gy in 12 fractions26 days 16 clearance of

hematuria

bull Selection by performance status Palliation (pain and

hematuria) better with hypofractionated RT worse

survival

bull No important side effects

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 54

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung cancer

bull Control of hemoptysis in up to 80 of patients (Brundage

Can J Oncol 1996 Medical Research Council Lung Cancer Working Party

Br J Cancer 1992 Hoskin in Doyle et al Second Edition New York

Oxford University Press 1998 Langendijk Int J Radiat Oncol Biol Phys

2000)

bull Optimal dosefractionation

ndash Hypofractionated RT seems to be equally effective to multiple

fractions (Rees Clin Oncol (R Coll Radiol) 1997 Sundstrom JCO

2004 Phase III Stevens Australas Radiol 1995 Phase III studies of

the MRC (s above)

ndash 10 Gy Single fraction equally effective to multiple fractions less

toxic (Hoskin in Doyle et al Second Edition New York Oxford

University Press 1998 Medical Research Council Lung Cancer

Working Party Br J Cancer 1992)

ndash Mostly total dose of around 20 Gy (multiple fractions) or 8 Gy

single fraction recommended

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 55

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Van Lonkhuijzen

Radiother Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 56

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gynaecologic tumours

bull Cf review van Lonkhuijzen Radiother Oncol 2011

bull Consider intracavitary HDR brachytherapy

Rectal cancer

bull Up to 85 control of rectal bleeding (Hoskin in Doyle et al Second Edition New York Oxford University Press 1998)

Kaposi sarcoma

bull Good palliation for pain bleeding or edema TD 15-40 Gy SD 2 Gy gt90 response 70 complete remission (Review Becker et al Onkologie 2006)

Skin tumours (Miller in Doyle Oxford Textbook of Palliative Medicine New York Oxford University Press 1993)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 57

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duration of treatment effect

Lung cancer

bull Median duration of palliation 50 of remaining life span (30 Gy10d

27 Gy6d 17 Gy2 fract1w apart) (Medical Research Council Br J

Cancer 1991)

bull 1 fract 10 Gy vs 2 fract 85 Gy more patients need repeat RT (Medical Research Council Lung Cancer Working Party Br J Cancer 1992)

bull 417 pat need repeat RT within 3 m after 1x10 Gy (Scolaro Radiol

Med 1995)

Rec ovarian cancer

bull Median duration of palliation 4 m in 90 of patients until death (Corn Cancer 1994)

Cervical endometrial cancer

bull In 50 of patients pall Effect until death with 1-2x10 Gy

ndash Halle IJROBP 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 58

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull RT effective for improvement of

ndashThoracic symptoms (haemoptysis cough thoracic pain

dyspnoea airway obstruction) (Sirzeacuten Acta Oncol 2003 and others)

ndashQOL in about 13 of patients (Langendijk IJROBP 2000)

RT schedules

bull Systematic review (Fairchild JCO 264001-4011 2008)

ndash13 randomized trials 3473 patients

ndashdifferent RT schedules

ndashAim find optimal RT schedule for maximal palliation with

minimal toxicityneed for reirradiation

Thoracic symptoms

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 59

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz

Cancer

2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 60

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz Chow Hartsell Konski Cancer 2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 61

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemoptysis

bull Fig2 toux

733 689

812 802

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 62

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig3 doul thor 321 279

535 482

Cough

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 63

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 4 overall symptom burden

575 519

648 638

Thoracic pain

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 64

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 5 survie 1a

Cutoff (sensitivity analysis) BED[10] 35Gy vs LD

100 162

555 609

Overall symptom burden

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 65

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cutoff BED[10] 35Gy vs LD

265 217

Overall survival at 1y

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 66

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 7 Tox dysphagie

Cutoff BED[10] 30Gy vs LD

205 149

about x 2

Toxicity (dysphagia)

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 67

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomized trial 250 patients (Falk BMJ 2002)

bull Locally advanced non resectable NSCLC with minimal thoracic symptoms

bull Immediate vs delayed RT (at symptom onset)

bull In delayed arm 56 of patients died without RT

bull No difference in QOL odr OS

bull More acute toxicity in immediate RT arm

Randomized trial (Sundstrom Radiother Oncol 2005)

bull Advanced NSCLC

bull 2 RT schedules (5x4Gy vs 2x85 Gy) immediate RT

bull Stratification according to presenceabsence of thoracic symptoms

bull In asymptomatic patients no long term symptom control but important dysphagia

Timing

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 68

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull in 97 malignant

bull in 5-10 of lung cancer patients

bull Histology (exclude benign disease RT-chemosensible tumours

bull Generally spontanous improvement of symptoms by formation of collaterals

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 69

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Treatment

1 symptomatic

bull steroids

bull diuretics

bull Elevation of headthorax

2 causal bull chemotherapy (SCLC

lymphomas germinal tumours)

bull Endovascular stent placement

bull radiotherapy Palliative care in lung cancer ACCP

evidence- based clinical practice guidelines

(2nd edition)

Kvale Chest 2007

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 70

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

Radiotherapy

bull Mostly clinical response within 72 h

bull Complete clinical response at 2 w in 78 of patients with SCLC

and 63 of patients with NSCLC

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 71

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 72

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 73

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duhamel Atlas clinique des maladies

des voies aeacuteriennes Elsevier

wwwupmccancercenterscom

Endobronchial brachytherapy

Cochrane analysis (Cardona The Cochrane

Library 2008)

bull No improved

symptom relief by

addition of

endobronchial

brachytherapy to

EBRT

bull Indicated in selected

patients pretreated

by EBRT with

central

endobronchial

obstruction

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 74

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Ozkok Lung Cancer 2008

Endobronchial brachytherapy

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Take home lung cancer

Dosefractionation

bull Minimum 10x3 Gy 5xw or equivalent

ndash better symptom control and better overall survival

ndash But more toxicity

bull Short schedule for symptom control and limited toxicity

ndashPoor performance status limited life expectancy

Timing

bull RT at the moment of symptom onset

bull No place for bdquoprophylactic palliative RTldquo according to evidence based guidelines

ndashExceptions

bull Young patient good PS aim of local control

bull Imminent symptoms (superior vena cava syndrome central airway obstruction

Rodrigues Pract Rad Oncol 2011

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

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Homs Eur J CancerLancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 90

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

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Scoccianti Radiother Oncol 2012

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Page 3: SRO Tutorial Palliative Care 04.05.2012 Palliative Radiotherapy · 2018-02-22 · SRO Tutorial Palliative Care – Palliative Radiotherapy 30 Jacqueline Vock, Universitätsklinik

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Importance of palliative radiotherapy in a radiation

oncology department

bull Importance of (palliative) radiotherapy in the treatment of

cancer patients

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Radiotherapy 50 of patients

Palliative

25

curative

26

Courtesy of D Aebersold

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 5

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brainstorming

bull Differences between curative and palliative radiotherapy

bull What aspects have to be considered

bull Aimsindications of palliative radiotherapy

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 6

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Aims

ndashReduction of existing symptoms

ndashPrevention of immanent symptoms

bull Important

bull Consider

ndashPerformance status

ndashLife expectancy

ndashToxicity

ndashDuration of palliation

bull Quality of life What is important for the patient

bull Not too long (hypofractionation) little toxicity

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 7

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Pain

ndashBone

ndashSoft tissue

bull Neurologic compression

ndashSpinal cord

ndashPeripheral nerves

ndashBrain

bull Haemorrhage

bull Symptoms caused by obstruction

ndashAirways dyspnoea

ndashSwallowing route dysphagia

ndashVenous flow superiorinferior cava syndrome

ndashUrinary tract urinary retention renal failure

bull Cosmesis odour in tumours infiltrating the skin

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 8

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz Cancer J 2010

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 9

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz Cancer J 2010

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 10

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Van Oorschot Sem Oncol 2011

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SRO Tutorial Palliative Care ndash Palliative Radiotherapy 12

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cancer 2010

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastases

bull What tumours

bull Does RT work

bull Causal and symptomatic effect (anti-tumour anti-

inflammatory)

bull How do you treat them Why Studies on fractionation

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 14

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

RT of bone metastases -

fractionation

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 15

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lievens RO 2000

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 16

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lievens RO 2000

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 17

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Konski Semin Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 18

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Konski Semin Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 19

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Overall

response

rate

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 20

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Complete

response

rate

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 21

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Retreat

ment

rate

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull EBRT significant palliation of painful bone metastasis in

50-80 of patients complete pain relief in up to 13 of

patients (Chow JCO 2007)

bull Optimal fractionation RT technique combination with other

treatment options

bull Systematic review combined with expert opinions

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 23

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Uncomplicated bone

metastasis

Single vs multiple

fractions

bull Pain relief

equivalent

bull Long term toxicity

equivalent

bull Single fraction

optimal patient and

caregiver

convenience

bull Retreatment rate

20 vs 8

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 24

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Repeat treatment of painful spinal metastasis

bull Pain relief in 46-80

bull Cave dose to spinal cord

bull Dosefractionation unclear

bull Recommendation prospective trial

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 25

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Comparable fracture risk Chow Clin Oncol 2012

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 26

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Comparable risk of

spinal cord

compression

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 27

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SBRT of spinal metastasis

bull Mostly retrospective single-institution series

bull Recommendation prospective trial

bull Not primary treatment for spinal met causing spinal cord

compression

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 28

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Radionuclides

bull Important often underused option for multifocal bone

metastasis

bull For osteoblastic metastasis

bull Based on available data do not obviate need for EBRT

bull Recommendation prospective studies on prophylactic use

of radiopharmaceuticals in patients with limited bone

metastases combination with other systemic agents

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 29

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 30

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Biphosphonates

bull Several prospective studies on concurrent EBRT and

biphosphonates successful pain relief promotion of re-

ossification of damaged bone acceptable risk of toxicity

bull Not shown that combination better than EBRT alone for

pain relief

bull Recommendation prospective trial on optimum RT

fractionation EBRT versus radionuclides dose and

duration of biphosphonates and scheduling

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 31

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 32

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Denosumab

Lipton Curr Opp Supp Pall Care 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 33

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lipton Curr Opp Supp

Pall Care 2011

Denosumab versus

Zoledronate

Prevention of SREs (path fracture RT or OP to bone

spinal cord compression)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 34

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Breast

superior

Prostate

superior

Other solid

tumors or

multiple

myeloma

non inferior

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 35

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Vertebroplastykyphoplasty

bull No prospective data to suggest

that vertkyph obviates the

need for EBRT in painful bone

met

bull Small series of patients treated

by vertkyph plus EBRT

bull Recommendation prospective

trials on patient selection

efficacy toxicity and timing of

vertkyph and RT

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 36

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 37

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Non inferiority study

bull 272 patients randomized

Neuropathic pain

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 38

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 39

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 40

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Spinal cord compression

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 41

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 42

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 43

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Patchell Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 44

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

RT short versus

long course

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 45

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 46

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 47

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 48

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 49

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 50

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull SRO tutorial CNS PD Dr A Pica

bull ScocciantiRicardi Radiother Oncol 2012 Review

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 51

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemorrhage

bull Bleeding in 6-10 of patients with advanced

cancer (Pereira et al Topics in Palliative Care Vol 4 New York

Oxford University Press 2000)

bull haemoptysis

bull haematemesis

bull haematocheziamelaena

bull vaginal bleeding

bull haematuria

bull bleeding in ulcerated skin lesions

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 52

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Mechanisms of haemostatic radiotherapy

bull Sparse literature

bull Coagulation activationsup1

ndash Oxydative endothelial damage

ndash Activation of thrombocytes

ndash Activation of inflammation

bull Long term anti-angiogenetic

sup1 Hallahan et al Oncology (Huntingt) 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 53

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Prostate cancer

bull Reduction of pain and bleeding in hormone refractory

prostate cancer (Kynaston Br J Urol 1990 Kawakami Nippon

Hinyokika Gakkai Zasshi 1993 Kalapurakal Int J Radiat Oncol Biol Phys

2003)

bull 100 improvement in patients with important hematuria (Carlton J Urol 1972)

Bladder cancer (Srinivasan et al Clin Oncol (R Coll Radiol) 1994)

bull 17 Gy in 2 fractions3 days 59 clearance of hematuria

bull 45 Gy in 12 fractions26 days 16 clearance of

hematuria

bull Selection by performance status Palliation (pain and

hematuria) better with hypofractionated RT worse

survival

bull No important side effects

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 54

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung cancer

bull Control of hemoptysis in up to 80 of patients (Brundage

Can J Oncol 1996 Medical Research Council Lung Cancer Working Party

Br J Cancer 1992 Hoskin in Doyle et al Second Edition New York

Oxford University Press 1998 Langendijk Int J Radiat Oncol Biol Phys

2000)

bull Optimal dosefractionation

ndash Hypofractionated RT seems to be equally effective to multiple

fractions (Rees Clin Oncol (R Coll Radiol) 1997 Sundstrom JCO

2004 Phase III Stevens Australas Radiol 1995 Phase III studies of

the MRC (s above)

ndash 10 Gy Single fraction equally effective to multiple fractions less

toxic (Hoskin in Doyle et al Second Edition New York Oxford

University Press 1998 Medical Research Council Lung Cancer

Working Party Br J Cancer 1992)

ndash Mostly total dose of around 20 Gy (multiple fractions) or 8 Gy

single fraction recommended

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 55

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Van Lonkhuijzen

Radiother Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 56

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gynaecologic tumours

bull Cf review van Lonkhuijzen Radiother Oncol 2011

bull Consider intracavitary HDR brachytherapy

Rectal cancer

bull Up to 85 control of rectal bleeding (Hoskin in Doyle et al Second Edition New York Oxford University Press 1998)

Kaposi sarcoma

bull Good palliation for pain bleeding or edema TD 15-40 Gy SD 2 Gy gt90 response 70 complete remission (Review Becker et al Onkologie 2006)

Skin tumours (Miller in Doyle Oxford Textbook of Palliative Medicine New York Oxford University Press 1993)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 57

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duration of treatment effect

Lung cancer

bull Median duration of palliation 50 of remaining life span (30 Gy10d

27 Gy6d 17 Gy2 fract1w apart) (Medical Research Council Br J

Cancer 1991)

bull 1 fract 10 Gy vs 2 fract 85 Gy more patients need repeat RT (Medical Research Council Lung Cancer Working Party Br J Cancer 1992)

bull 417 pat need repeat RT within 3 m after 1x10 Gy (Scolaro Radiol

Med 1995)

Rec ovarian cancer

bull Median duration of palliation 4 m in 90 of patients until death (Corn Cancer 1994)

Cervical endometrial cancer

bull In 50 of patients pall Effect until death with 1-2x10 Gy

ndash Halle IJROBP 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 58

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull RT effective for improvement of

ndashThoracic symptoms (haemoptysis cough thoracic pain

dyspnoea airway obstruction) (Sirzeacuten Acta Oncol 2003 and others)

ndashQOL in about 13 of patients (Langendijk IJROBP 2000)

RT schedules

bull Systematic review (Fairchild JCO 264001-4011 2008)

ndash13 randomized trials 3473 patients

ndashdifferent RT schedules

ndashAim find optimal RT schedule for maximal palliation with

minimal toxicityneed for reirradiation

Thoracic symptoms

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 59

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz

Cancer

2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 60

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz Chow Hartsell Konski Cancer 2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 61

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemoptysis

bull Fig2 toux

733 689

812 802

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 62

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig3 doul thor 321 279

535 482

Cough

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 63

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 4 overall symptom burden

575 519

648 638

Thoracic pain

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 64

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 5 survie 1a

Cutoff (sensitivity analysis) BED[10] 35Gy vs LD

100 162

555 609

Overall symptom burden

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 65

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cutoff BED[10] 35Gy vs LD

265 217

Overall survival at 1y

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 66

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 7 Tox dysphagie

Cutoff BED[10] 30Gy vs LD

205 149

about x 2

Toxicity (dysphagia)

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 67

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomized trial 250 patients (Falk BMJ 2002)

bull Locally advanced non resectable NSCLC with minimal thoracic symptoms

bull Immediate vs delayed RT (at symptom onset)

bull In delayed arm 56 of patients died without RT

bull No difference in QOL odr OS

bull More acute toxicity in immediate RT arm

Randomized trial (Sundstrom Radiother Oncol 2005)

bull Advanced NSCLC

bull 2 RT schedules (5x4Gy vs 2x85 Gy) immediate RT

bull Stratification according to presenceabsence of thoracic symptoms

bull In asymptomatic patients no long term symptom control but important dysphagia

Timing

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 68

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull in 97 malignant

bull in 5-10 of lung cancer patients

bull Histology (exclude benign disease RT-chemosensible tumours

bull Generally spontanous improvement of symptoms by formation of collaterals

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 69

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Treatment

1 symptomatic

bull steroids

bull diuretics

bull Elevation of headthorax

2 causal bull chemotherapy (SCLC

lymphomas germinal tumours)

bull Endovascular stent placement

bull radiotherapy Palliative care in lung cancer ACCP

evidence- based clinical practice guidelines

(2nd edition)

Kvale Chest 2007

Superior vena cava syndrome

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

Radiotherapy

bull Mostly clinical response within 72 h

bull Complete clinical response at 2 w in 78 of patients with SCLC

and 63 of patients with NSCLC

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duhamel Atlas clinique des maladies

des voies aeacuteriennes Elsevier

wwwupmccancercenterscom

Endobronchial brachytherapy

Cochrane analysis (Cardona The Cochrane

Library 2008)

bull No improved

symptom relief by

addition of

endobronchial

brachytherapy to

EBRT

bull Indicated in selected

patients pretreated

by EBRT with

central

endobronchial

obstruction

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Ozkok Lung Cancer 2008

Endobronchial brachytherapy

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Take home lung cancer

Dosefractionation

bull Minimum 10x3 Gy 5xw or equivalent

ndash better symptom control and better overall survival

ndash But more toxicity

bull Short schedule for symptom control and limited toxicity

ndashPoor performance status limited life expectancy

Timing

bull RT at the moment of symptom onset

bull No place for bdquoprophylactic palliative RTldquo according to evidence based guidelines

ndashExceptions

bull Young patient good PS aim of local control

bull Imminent symptoms (superior vena cava syndrome central airway obstruction

Rodrigues Pract Rad Oncol 2011

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 80

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

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Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 82

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 83

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 84

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 90

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

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Scoccianti Radiother Oncol 2012

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SRO Tutorial Palliative Care ndash Palliative Radiotherapy 101

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 102

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 103

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 104

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Page 4: SRO Tutorial Palliative Care 04.05.2012 Palliative Radiotherapy · 2018-02-22 · SRO Tutorial Palliative Care – Palliative Radiotherapy 30 Jacqueline Vock, Universitätsklinik

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Radiotherapy 50 of patients

Palliative

25

curative

26

Courtesy of D Aebersold

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 5

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brainstorming

bull Differences between curative and palliative radiotherapy

bull What aspects have to be considered

bull Aimsindications of palliative radiotherapy

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 6

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Aims

ndashReduction of existing symptoms

ndashPrevention of immanent symptoms

bull Important

bull Consider

ndashPerformance status

ndashLife expectancy

ndashToxicity

ndashDuration of palliation

bull Quality of life What is important for the patient

bull Not too long (hypofractionation) little toxicity

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 7

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Pain

ndashBone

ndashSoft tissue

bull Neurologic compression

ndashSpinal cord

ndashPeripheral nerves

ndashBrain

bull Haemorrhage

bull Symptoms caused by obstruction

ndashAirways dyspnoea

ndashSwallowing route dysphagia

ndashVenous flow superiorinferior cava syndrome

ndashUrinary tract urinary retention renal failure

bull Cosmesis odour in tumours infiltrating the skin

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 8

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz Cancer J 2010

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 9

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz Cancer J 2010

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 10

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Van Oorschot Sem Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 11

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 12

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cancer 2010

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 13

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastases

bull What tumours

bull Does RT work

bull Causal and symptomatic effect (anti-tumour anti-

inflammatory)

bull How do you treat them Why Studies on fractionation

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 14

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

RT of bone metastases -

fractionation

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 15

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lievens RO 2000

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 16

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lievens RO 2000

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 17

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Konski Semin Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 18

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Konski Semin Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 19

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Overall

response

rate

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 20

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Complete

response

rate

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 21

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Retreat

ment

rate

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 22

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull EBRT significant palliation of painful bone metastasis in

50-80 of patients complete pain relief in up to 13 of

patients (Chow JCO 2007)

bull Optimal fractionation RT technique combination with other

treatment options

bull Systematic review combined with expert opinions

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 23

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Uncomplicated bone

metastasis

Single vs multiple

fractions

bull Pain relief

equivalent

bull Long term toxicity

equivalent

bull Single fraction

optimal patient and

caregiver

convenience

bull Retreatment rate

20 vs 8

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 24

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Repeat treatment of painful spinal metastasis

bull Pain relief in 46-80

bull Cave dose to spinal cord

bull Dosefractionation unclear

bull Recommendation prospective trial

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 25

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Comparable fracture risk Chow Clin Oncol 2012

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 26

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Comparable risk of

spinal cord

compression

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 27

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SBRT of spinal metastasis

bull Mostly retrospective single-institution series

bull Recommendation prospective trial

bull Not primary treatment for spinal met causing spinal cord

compression

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 28

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Radionuclides

bull Important often underused option for multifocal bone

metastasis

bull For osteoblastic metastasis

bull Based on available data do not obviate need for EBRT

bull Recommendation prospective studies on prophylactic use

of radiopharmaceuticals in patients with limited bone

metastases combination with other systemic agents

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 29

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 30

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Biphosphonates

bull Several prospective studies on concurrent EBRT and

biphosphonates successful pain relief promotion of re-

ossification of damaged bone acceptable risk of toxicity

bull Not shown that combination better than EBRT alone for

pain relief

bull Recommendation prospective trial on optimum RT

fractionation EBRT versus radionuclides dose and

duration of biphosphonates and scheduling

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 31

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 32

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Denosumab

Lipton Curr Opp Supp Pall Care 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 33

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lipton Curr Opp Supp

Pall Care 2011

Denosumab versus

Zoledronate

Prevention of SREs (path fracture RT or OP to bone

spinal cord compression)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 34

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Breast

superior

Prostate

superior

Other solid

tumors or

multiple

myeloma

non inferior

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 35

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Vertebroplastykyphoplasty

bull No prospective data to suggest

that vertkyph obviates the

need for EBRT in painful bone

met

bull Small series of patients treated

by vertkyph plus EBRT

bull Recommendation prospective

trials on patient selection

efficacy toxicity and timing of

vertkyph and RT

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 36

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 37

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Non inferiority study

bull 272 patients randomized

Neuropathic pain

Roos Radiother Oncol 2005

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 39

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 40

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Spinal cord compression

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 41

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 42

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 43

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Patchell Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 44

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

RT short versus

long course

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 45

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 46

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 47

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 48

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 49

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 50

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull SRO tutorial CNS PD Dr A Pica

bull ScocciantiRicardi Radiother Oncol 2012 Review

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 51

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemorrhage

bull Bleeding in 6-10 of patients with advanced

cancer (Pereira et al Topics in Palliative Care Vol 4 New York

Oxford University Press 2000)

bull haemoptysis

bull haematemesis

bull haematocheziamelaena

bull vaginal bleeding

bull haematuria

bull bleeding in ulcerated skin lesions

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 52

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Mechanisms of haemostatic radiotherapy

bull Sparse literature

bull Coagulation activationsup1

ndash Oxydative endothelial damage

ndash Activation of thrombocytes

ndash Activation of inflammation

bull Long term anti-angiogenetic

sup1 Hallahan et al Oncology (Huntingt) 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 53

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Prostate cancer

bull Reduction of pain and bleeding in hormone refractory

prostate cancer (Kynaston Br J Urol 1990 Kawakami Nippon

Hinyokika Gakkai Zasshi 1993 Kalapurakal Int J Radiat Oncol Biol Phys

2003)

bull 100 improvement in patients with important hematuria (Carlton J Urol 1972)

Bladder cancer (Srinivasan et al Clin Oncol (R Coll Radiol) 1994)

bull 17 Gy in 2 fractions3 days 59 clearance of hematuria

bull 45 Gy in 12 fractions26 days 16 clearance of

hematuria

bull Selection by performance status Palliation (pain and

hematuria) better with hypofractionated RT worse

survival

bull No important side effects

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 54

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung cancer

bull Control of hemoptysis in up to 80 of patients (Brundage

Can J Oncol 1996 Medical Research Council Lung Cancer Working Party

Br J Cancer 1992 Hoskin in Doyle et al Second Edition New York

Oxford University Press 1998 Langendijk Int J Radiat Oncol Biol Phys

2000)

bull Optimal dosefractionation

ndash Hypofractionated RT seems to be equally effective to multiple

fractions (Rees Clin Oncol (R Coll Radiol) 1997 Sundstrom JCO

2004 Phase III Stevens Australas Radiol 1995 Phase III studies of

the MRC (s above)

ndash 10 Gy Single fraction equally effective to multiple fractions less

toxic (Hoskin in Doyle et al Second Edition New York Oxford

University Press 1998 Medical Research Council Lung Cancer

Working Party Br J Cancer 1992)

ndash Mostly total dose of around 20 Gy (multiple fractions) or 8 Gy

single fraction recommended

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 55

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Van Lonkhuijzen

Radiother Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 56

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gynaecologic tumours

bull Cf review van Lonkhuijzen Radiother Oncol 2011

bull Consider intracavitary HDR brachytherapy

Rectal cancer

bull Up to 85 control of rectal bleeding (Hoskin in Doyle et al Second Edition New York Oxford University Press 1998)

Kaposi sarcoma

bull Good palliation for pain bleeding or edema TD 15-40 Gy SD 2 Gy gt90 response 70 complete remission (Review Becker et al Onkologie 2006)

Skin tumours (Miller in Doyle Oxford Textbook of Palliative Medicine New York Oxford University Press 1993)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 57

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duration of treatment effect

Lung cancer

bull Median duration of palliation 50 of remaining life span (30 Gy10d

27 Gy6d 17 Gy2 fract1w apart) (Medical Research Council Br J

Cancer 1991)

bull 1 fract 10 Gy vs 2 fract 85 Gy more patients need repeat RT (Medical Research Council Lung Cancer Working Party Br J Cancer 1992)

bull 417 pat need repeat RT within 3 m after 1x10 Gy (Scolaro Radiol

Med 1995)

Rec ovarian cancer

bull Median duration of palliation 4 m in 90 of patients until death (Corn Cancer 1994)

Cervical endometrial cancer

bull In 50 of patients pall Effect until death with 1-2x10 Gy

ndash Halle IJROBP 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 58

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull RT effective for improvement of

ndashThoracic symptoms (haemoptysis cough thoracic pain

dyspnoea airway obstruction) (Sirzeacuten Acta Oncol 2003 and others)

ndashQOL in about 13 of patients (Langendijk IJROBP 2000)

RT schedules

bull Systematic review (Fairchild JCO 264001-4011 2008)

ndash13 randomized trials 3473 patients

ndashdifferent RT schedules

ndashAim find optimal RT schedule for maximal palliation with

minimal toxicityneed for reirradiation

Thoracic symptoms

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz

Cancer

2007

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz Chow Hartsell Konski Cancer 2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 61

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemoptysis

bull Fig2 toux

733 689

812 802

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 62

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig3 doul thor 321 279

535 482

Cough

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 63

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 4 overall symptom burden

575 519

648 638

Thoracic pain

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 64

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 5 survie 1a

Cutoff (sensitivity analysis) BED[10] 35Gy vs LD

100 162

555 609

Overall symptom burden

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 65

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cutoff BED[10] 35Gy vs LD

265 217

Overall survival at 1y

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 66

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 7 Tox dysphagie

Cutoff BED[10] 30Gy vs LD

205 149

about x 2

Toxicity (dysphagia)

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 67

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomized trial 250 patients (Falk BMJ 2002)

bull Locally advanced non resectable NSCLC with minimal thoracic symptoms

bull Immediate vs delayed RT (at symptom onset)

bull In delayed arm 56 of patients died without RT

bull No difference in QOL odr OS

bull More acute toxicity in immediate RT arm

Randomized trial (Sundstrom Radiother Oncol 2005)

bull Advanced NSCLC

bull 2 RT schedules (5x4Gy vs 2x85 Gy) immediate RT

bull Stratification according to presenceabsence of thoracic symptoms

bull In asymptomatic patients no long term symptom control but important dysphagia

Timing

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 68

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull in 97 malignant

bull in 5-10 of lung cancer patients

bull Histology (exclude benign disease RT-chemosensible tumours

bull Generally spontanous improvement of symptoms by formation of collaterals

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 69

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Treatment

1 symptomatic

bull steroids

bull diuretics

bull Elevation of headthorax

2 causal bull chemotherapy (SCLC

lymphomas germinal tumours)

bull Endovascular stent placement

bull radiotherapy Palliative care in lung cancer ACCP

evidence- based clinical practice guidelines

(2nd edition)

Kvale Chest 2007

Superior vena cava syndrome

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

Radiotherapy

bull Mostly clinical response within 72 h

bull Complete clinical response at 2 w in 78 of patients with SCLC

and 63 of patients with NSCLC

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duhamel Atlas clinique des maladies

des voies aeacuteriennes Elsevier

wwwupmccancercenterscom

Endobronchial brachytherapy

Cochrane analysis (Cardona The Cochrane

Library 2008)

bull No improved

symptom relief by

addition of

endobronchial

brachytherapy to

EBRT

bull Indicated in selected

patients pretreated

by EBRT with

central

endobronchial

obstruction

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 74

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Ozkok Lung Cancer 2008

Endobronchial brachytherapy

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Take home lung cancer

Dosefractionation

bull Minimum 10x3 Gy 5xw or equivalent

ndash better symptom control and better overall survival

ndash But more toxicity

bull Short schedule for symptom control and limited toxicity

ndashPoor performance status limited life expectancy

Timing

bull RT at the moment of symptom onset

bull No place for bdquoprophylactic palliative RTldquo according to evidence based guidelines

ndashExceptions

bull Young patient good PS aim of local control

bull Imminent symptoms (superior vena cava syndrome central airway obstruction

Rodrigues Pract Rad Oncol 2011

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

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Homs Eur J CancerLancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

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Randomisierte Studien

Homs Lancet 2004

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Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

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Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

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Scoccianti Radiother Oncol 2012

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SRO Tutorial Palliative Care ndash Palliative Radiotherapy 102

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brainstorming

bull Differences between curative and palliative radiotherapy

bull What aspects have to be considered

bull Aimsindications of palliative radiotherapy

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 6

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Aims

ndashReduction of existing symptoms

ndashPrevention of immanent symptoms

bull Important

bull Consider

ndashPerformance status

ndashLife expectancy

ndashToxicity

ndashDuration of palliation

bull Quality of life What is important for the patient

bull Not too long (hypofractionation) little toxicity

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 7

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Pain

ndashBone

ndashSoft tissue

bull Neurologic compression

ndashSpinal cord

ndashPeripheral nerves

ndashBrain

bull Haemorrhage

bull Symptoms caused by obstruction

ndashAirways dyspnoea

ndashSwallowing route dysphagia

ndashVenous flow superiorinferior cava syndrome

ndashUrinary tract urinary retention renal failure

bull Cosmesis odour in tumours infiltrating the skin

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 8

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz Cancer J 2010

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 9

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Lutz Cancer J 2010

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 10

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Van Oorschot Sem Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 11

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SRO Tutorial Palliative Care ndash Palliative Radiotherapy 12

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cancer 2010

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 13

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastases

bull What tumours

bull Does RT work

bull Causal and symptomatic effect (anti-tumour anti-

inflammatory)

bull How do you treat them Why Studies on fractionation

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 14

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

RT of bone metastases -

fractionation

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lievens RO 2000

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lievens RO 2000

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 17

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Konski Semin Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 18

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Konski Semin Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 19

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Overall

response

rate

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 20

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Complete

response

rate

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 21

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Retreat

ment

rate

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 22

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull EBRT significant palliation of painful bone metastasis in

50-80 of patients complete pain relief in up to 13 of

patients (Chow JCO 2007)

bull Optimal fractionation RT technique combination with other

treatment options

bull Systematic review combined with expert opinions

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 23

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Uncomplicated bone

metastasis

Single vs multiple

fractions

bull Pain relief

equivalent

bull Long term toxicity

equivalent

bull Single fraction

optimal patient and

caregiver

convenience

bull Retreatment rate

20 vs 8

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 24

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Repeat treatment of painful spinal metastasis

bull Pain relief in 46-80

bull Cave dose to spinal cord

bull Dosefractionation unclear

bull Recommendation prospective trial

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 25

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Comparable fracture risk Chow Clin Oncol 2012

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 26

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Comparable risk of

spinal cord

compression

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 27

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SBRT of spinal metastasis

bull Mostly retrospective single-institution series

bull Recommendation prospective trial

bull Not primary treatment for spinal met causing spinal cord

compression

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 28

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Radionuclides

bull Important often underused option for multifocal bone

metastasis

bull For osteoblastic metastasis

bull Based on available data do not obviate need for EBRT

bull Recommendation prospective studies on prophylactic use

of radiopharmaceuticals in patients with limited bone

metastases combination with other systemic agents

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 29

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 30

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Biphosphonates

bull Several prospective studies on concurrent EBRT and

biphosphonates successful pain relief promotion of re-

ossification of damaged bone acceptable risk of toxicity

bull Not shown that combination better than EBRT alone for

pain relief

bull Recommendation prospective trial on optimum RT

fractionation EBRT versus radionuclides dose and

duration of biphosphonates and scheduling

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 31

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 32

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Denosumab

Lipton Curr Opp Supp Pall Care 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 33

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lipton Curr Opp Supp

Pall Care 2011

Denosumab versus

Zoledronate

Prevention of SREs (path fracture RT or OP to bone

spinal cord compression)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 34

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Breast

superior

Prostate

superior

Other solid

tumors or

multiple

myeloma

non inferior

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 35

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Vertebroplastykyphoplasty

bull No prospective data to suggest

that vertkyph obviates the

need for EBRT in painful bone

met

bull Small series of patients treated

by vertkyph plus EBRT

bull Recommendation prospective

trials on patient selection

efficacy toxicity and timing of

vertkyph and RT

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 36

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 37

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Non inferiority study

bull 272 patients randomized

Neuropathic pain

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 38

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 39

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 40

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Spinal cord compression

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 41

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 42

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 43

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Patchell Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 44

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

RT short versus

long course

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 45

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 46

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 47

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 48

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 49

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 50

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull SRO tutorial CNS PD Dr A Pica

bull ScocciantiRicardi Radiother Oncol 2012 Review

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 51

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemorrhage

bull Bleeding in 6-10 of patients with advanced

cancer (Pereira et al Topics in Palliative Care Vol 4 New York

Oxford University Press 2000)

bull haemoptysis

bull haematemesis

bull haematocheziamelaena

bull vaginal bleeding

bull haematuria

bull bleeding in ulcerated skin lesions

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 52

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Mechanisms of haemostatic radiotherapy

bull Sparse literature

bull Coagulation activationsup1

ndash Oxydative endothelial damage

ndash Activation of thrombocytes

ndash Activation of inflammation

bull Long term anti-angiogenetic

sup1 Hallahan et al Oncology (Huntingt) 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 53

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Prostate cancer

bull Reduction of pain and bleeding in hormone refractory

prostate cancer (Kynaston Br J Urol 1990 Kawakami Nippon

Hinyokika Gakkai Zasshi 1993 Kalapurakal Int J Radiat Oncol Biol Phys

2003)

bull 100 improvement in patients with important hematuria (Carlton J Urol 1972)

Bladder cancer (Srinivasan et al Clin Oncol (R Coll Radiol) 1994)

bull 17 Gy in 2 fractions3 days 59 clearance of hematuria

bull 45 Gy in 12 fractions26 days 16 clearance of

hematuria

bull Selection by performance status Palliation (pain and

hematuria) better with hypofractionated RT worse

survival

bull No important side effects

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 54

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung cancer

bull Control of hemoptysis in up to 80 of patients (Brundage

Can J Oncol 1996 Medical Research Council Lung Cancer Working Party

Br J Cancer 1992 Hoskin in Doyle et al Second Edition New York

Oxford University Press 1998 Langendijk Int J Radiat Oncol Biol Phys

2000)

bull Optimal dosefractionation

ndash Hypofractionated RT seems to be equally effective to multiple

fractions (Rees Clin Oncol (R Coll Radiol) 1997 Sundstrom JCO

2004 Phase III Stevens Australas Radiol 1995 Phase III studies of

the MRC (s above)

ndash 10 Gy Single fraction equally effective to multiple fractions less

toxic (Hoskin in Doyle et al Second Edition New York Oxford

University Press 1998 Medical Research Council Lung Cancer

Working Party Br J Cancer 1992)

ndash Mostly total dose of around 20 Gy (multiple fractions) or 8 Gy

single fraction recommended

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 55

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Van Lonkhuijzen

Radiother Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 56

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gynaecologic tumours

bull Cf review van Lonkhuijzen Radiother Oncol 2011

bull Consider intracavitary HDR brachytherapy

Rectal cancer

bull Up to 85 control of rectal bleeding (Hoskin in Doyle et al Second Edition New York Oxford University Press 1998)

Kaposi sarcoma

bull Good palliation for pain bleeding or edema TD 15-40 Gy SD 2 Gy gt90 response 70 complete remission (Review Becker et al Onkologie 2006)

Skin tumours (Miller in Doyle Oxford Textbook of Palliative Medicine New York Oxford University Press 1993)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 57

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Duration of treatment effect

Lung cancer

bull Median duration of palliation 50 of remaining life span (30 Gy10d

27 Gy6d 17 Gy2 fract1w apart) (Medical Research Council Br J

Cancer 1991)

bull 1 fract 10 Gy vs 2 fract 85 Gy more patients need repeat RT (Medical Research Council Lung Cancer Working Party Br J Cancer 1992)

bull 417 pat need repeat RT within 3 m after 1x10 Gy (Scolaro Radiol

Med 1995)

Rec ovarian cancer

bull Median duration of palliation 4 m in 90 of patients until death (Corn Cancer 1994)

Cervical endometrial cancer

bull In 50 of patients pall Effect until death with 1-2x10 Gy

ndash Halle IJROBP 1986

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull RT effective for improvement of

ndashThoracic symptoms (haemoptysis cough thoracic pain

dyspnoea airway obstruction) (Sirzeacuten Acta Oncol 2003 and others)

ndashQOL in about 13 of patients (Langendijk IJROBP 2000)

RT schedules

bull Systematic review (Fairchild JCO 264001-4011 2008)

ndash13 randomized trials 3473 patients

ndashdifferent RT schedules

ndashAim find optimal RT schedule for maximal palliation with

minimal toxicityneed for reirradiation

Thoracic symptoms

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz

Cancer

2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 60

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz Chow Hartsell Konski Cancer 2007

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Haemoptysis

bull Fig2 toux

733 689

812 802

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 62

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig3 doul thor 321 279

535 482

Cough

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 63

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 4 overall symptom burden

575 519

648 638

Thoracic pain

Fairchild JCO 2008

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 5 survie 1a

Cutoff (sensitivity analysis) BED[10] 35Gy vs LD

100 162

555 609

Overall symptom burden

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 65

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cutoff BED[10] 35Gy vs LD

265 217

Overall survival at 1y

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 66

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 7 Tox dysphagie

Cutoff BED[10] 30Gy vs LD

205 149

about x 2

Toxicity (dysphagia)

Fairchild JCO 2008

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomized trial 250 patients (Falk BMJ 2002)

bull Locally advanced non resectable NSCLC with minimal thoracic symptoms

bull Immediate vs delayed RT (at symptom onset)

bull In delayed arm 56 of patients died without RT

bull No difference in QOL odr OS

bull More acute toxicity in immediate RT arm

Randomized trial (Sundstrom Radiother Oncol 2005)

bull Advanced NSCLC

bull 2 RT schedules (5x4Gy vs 2x85 Gy) immediate RT

bull Stratification according to presenceabsence of thoracic symptoms

bull In asymptomatic patients no long term symptom control but important dysphagia

Timing

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull in 97 malignant

bull in 5-10 of lung cancer patients

bull Histology (exclude benign disease RT-chemosensible tumours

bull Generally spontanous improvement of symptoms by formation of collaterals

Superior vena cava syndrome

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Treatment

1 symptomatic

bull steroids

bull diuretics

bull Elevation of headthorax

2 causal bull chemotherapy (SCLC

lymphomas germinal tumours)

bull Endovascular stent placement

bull radiotherapy Palliative care in lung cancer ACCP

evidence- based clinical practice guidelines

(2nd edition)

Kvale Chest 2007

Superior vena cava syndrome

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

Radiotherapy

bull Mostly clinical response within 72 h

bull Complete clinical response at 2 w in 78 of patients with SCLC

and 63 of patients with NSCLC

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

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Duhamel Atlas clinique des maladies

des voies aeacuteriennes Elsevier

wwwupmccancercenterscom

Endobronchial brachytherapy

Cochrane analysis (Cardona The Cochrane

Library 2008)

bull No improved

symptom relief by

addition of

endobronchial

brachytherapy to

EBRT

bull Indicated in selected

patients pretreated

by EBRT with

central

endobronchial

obstruction

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Ozkok Lung Cancer 2008

Endobronchial brachytherapy

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Take home lung cancer

Dosefractionation

bull Minimum 10x3 Gy 5xw or equivalent

ndash better symptom control and better overall survival

ndash But more toxicity

bull Short schedule for symptom control and limited toxicity

ndashPoor performance status limited life expectancy

Timing

bull RT at the moment of symptom onset

bull No place for bdquoprophylactic palliative RTldquo according to evidence based guidelines

ndashExceptions

bull Young patient good PS aim of local control

bull Imminent symptoms (superior vena cava syndrome central airway obstruction

Rodrigues Pract Rad Oncol 2011

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 80

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

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Homs Eur J CancerLancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 83

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 90

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 98

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

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Scoccianti Radiother Oncol 2012

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SRO Tutorial Palliative Care ndash Palliative Radiotherapy 6

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Aims

ndashReduction of existing symptoms

ndashPrevention of immanent symptoms

bull Important

bull Consider

ndashPerformance status

ndashLife expectancy

ndashToxicity

ndashDuration of palliation

bull Quality of life What is important for the patient

bull Not too long (hypofractionation) little toxicity

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 7

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Pain

ndashBone

ndashSoft tissue

bull Neurologic compression

ndashSpinal cord

ndashPeripheral nerves

ndashBrain

bull Haemorrhage

bull Symptoms caused by obstruction

ndashAirways dyspnoea

ndashSwallowing route dysphagia

ndashVenous flow superiorinferior cava syndrome

ndashUrinary tract urinary retention renal failure

bull Cosmesis odour in tumours infiltrating the skin

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 8

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz Cancer J 2010

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 9

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz Cancer J 2010

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 10

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Van Oorschot Sem Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 11

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 12

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cancer 2010

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 13

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastases

bull What tumours

bull Does RT work

bull Causal and symptomatic effect (anti-tumour anti-

inflammatory)

bull How do you treat them Why Studies on fractionation

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 14

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

RT of bone metastases -

fractionation

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 15

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lievens RO 2000

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 16

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lievens RO 2000

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 17

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Konski Semin Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 18

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Konski Semin Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 19

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Overall

response

rate

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 20

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Complete

response

rate

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 21

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Retreat

ment

rate

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 22

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull EBRT significant palliation of painful bone metastasis in

50-80 of patients complete pain relief in up to 13 of

patients (Chow JCO 2007)

bull Optimal fractionation RT technique combination with other

treatment options

bull Systematic review combined with expert opinions

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 23

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Uncomplicated bone

metastasis

Single vs multiple

fractions

bull Pain relief

equivalent

bull Long term toxicity

equivalent

bull Single fraction

optimal patient and

caregiver

convenience

bull Retreatment rate

20 vs 8

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 24

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Repeat treatment of painful spinal metastasis

bull Pain relief in 46-80

bull Cave dose to spinal cord

bull Dosefractionation unclear

bull Recommendation prospective trial

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 25

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Comparable fracture risk Chow Clin Oncol 2012

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 26

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Comparable risk of

spinal cord

compression

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 27

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SBRT of spinal metastasis

bull Mostly retrospective single-institution series

bull Recommendation prospective trial

bull Not primary treatment for spinal met causing spinal cord

compression

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 28

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Radionuclides

bull Important often underused option for multifocal bone

metastasis

bull For osteoblastic metastasis

bull Based on available data do not obviate need for EBRT

bull Recommendation prospective studies on prophylactic use

of radiopharmaceuticals in patients with limited bone

metastases combination with other systemic agents

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 29

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 30

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Biphosphonates

bull Several prospective studies on concurrent EBRT and

biphosphonates successful pain relief promotion of re-

ossification of damaged bone acceptable risk of toxicity

bull Not shown that combination better than EBRT alone for

pain relief

bull Recommendation prospective trial on optimum RT

fractionation EBRT versus radionuclides dose and

duration of biphosphonates and scheduling

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 31

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 32

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Denosumab

Lipton Curr Opp Supp Pall Care 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 33

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lipton Curr Opp Supp

Pall Care 2011

Denosumab versus

Zoledronate

Prevention of SREs (path fracture RT or OP to bone

spinal cord compression)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 34

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Breast

superior

Prostate

superior

Other solid

tumors or

multiple

myeloma

non inferior

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 35

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Vertebroplastykyphoplasty

bull No prospective data to suggest

that vertkyph obviates the

need for EBRT in painful bone

met

bull Small series of patients treated

by vertkyph plus EBRT

bull Recommendation prospective

trials on patient selection

efficacy toxicity and timing of

vertkyph and RT

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 36

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 37

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Non inferiority study

bull 272 patients randomized

Neuropathic pain

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 38

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 39

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 40

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Spinal cord compression

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 41

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 42

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 43

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Patchell Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 44

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

RT short versus

long course

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 45

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 46

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 47

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 48

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 49

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 50

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull SRO tutorial CNS PD Dr A Pica

bull ScocciantiRicardi Radiother Oncol 2012 Review

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 51

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemorrhage

bull Bleeding in 6-10 of patients with advanced

cancer (Pereira et al Topics in Palliative Care Vol 4 New York

Oxford University Press 2000)

bull haemoptysis

bull haematemesis

bull haematocheziamelaena

bull vaginal bleeding

bull haematuria

bull bleeding in ulcerated skin lesions

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 52

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Mechanisms of haemostatic radiotherapy

bull Sparse literature

bull Coagulation activationsup1

ndash Oxydative endothelial damage

ndash Activation of thrombocytes

ndash Activation of inflammation

bull Long term anti-angiogenetic

sup1 Hallahan et al Oncology (Huntingt) 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 53

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Prostate cancer

bull Reduction of pain and bleeding in hormone refractory

prostate cancer (Kynaston Br J Urol 1990 Kawakami Nippon

Hinyokika Gakkai Zasshi 1993 Kalapurakal Int J Radiat Oncol Biol Phys

2003)

bull 100 improvement in patients with important hematuria (Carlton J Urol 1972)

Bladder cancer (Srinivasan et al Clin Oncol (R Coll Radiol) 1994)

bull 17 Gy in 2 fractions3 days 59 clearance of hematuria

bull 45 Gy in 12 fractions26 days 16 clearance of

hematuria

bull Selection by performance status Palliation (pain and

hematuria) better with hypofractionated RT worse

survival

bull No important side effects

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 54

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung cancer

bull Control of hemoptysis in up to 80 of patients (Brundage

Can J Oncol 1996 Medical Research Council Lung Cancer Working Party

Br J Cancer 1992 Hoskin in Doyle et al Second Edition New York

Oxford University Press 1998 Langendijk Int J Radiat Oncol Biol Phys

2000)

bull Optimal dosefractionation

ndash Hypofractionated RT seems to be equally effective to multiple

fractions (Rees Clin Oncol (R Coll Radiol) 1997 Sundstrom JCO

2004 Phase III Stevens Australas Radiol 1995 Phase III studies of

the MRC (s above)

ndash 10 Gy Single fraction equally effective to multiple fractions less

toxic (Hoskin in Doyle et al Second Edition New York Oxford

University Press 1998 Medical Research Council Lung Cancer

Working Party Br J Cancer 1992)

ndash Mostly total dose of around 20 Gy (multiple fractions) or 8 Gy

single fraction recommended

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 55

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Van Lonkhuijzen

Radiother Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 56

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gynaecologic tumours

bull Cf review van Lonkhuijzen Radiother Oncol 2011

bull Consider intracavitary HDR brachytherapy

Rectal cancer

bull Up to 85 control of rectal bleeding (Hoskin in Doyle et al Second Edition New York Oxford University Press 1998)

Kaposi sarcoma

bull Good palliation for pain bleeding or edema TD 15-40 Gy SD 2 Gy gt90 response 70 complete remission (Review Becker et al Onkologie 2006)

Skin tumours (Miller in Doyle Oxford Textbook of Palliative Medicine New York Oxford University Press 1993)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 57

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duration of treatment effect

Lung cancer

bull Median duration of palliation 50 of remaining life span (30 Gy10d

27 Gy6d 17 Gy2 fract1w apart) (Medical Research Council Br J

Cancer 1991)

bull 1 fract 10 Gy vs 2 fract 85 Gy more patients need repeat RT (Medical Research Council Lung Cancer Working Party Br J Cancer 1992)

bull 417 pat need repeat RT within 3 m after 1x10 Gy (Scolaro Radiol

Med 1995)

Rec ovarian cancer

bull Median duration of palliation 4 m in 90 of patients until death (Corn Cancer 1994)

Cervical endometrial cancer

bull In 50 of patients pall Effect until death with 1-2x10 Gy

ndash Halle IJROBP 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 58

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull RT effective for improvement of

ndashThoracic symptoms (haemoptysis cough thoracic pain

dyspnoea airway obstruction) (Sirzeacuten Acta Oncol 2003 and others)

ndashQOL in about 13 of patients (Langendijk IJROBP 2000)

RT schedules

bull Systematic review (Fairchild JCO 264001-4011 2008)

ndash13 randomized trials 3473 patients

ndashdifferent RT schedules

ndashAim find optimal RT schedule for maximal palliation with

minimal toxicityneed for reirradiation

Thoracic symptoms

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 59

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz

Cancer

2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 60

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz Chow Hartsell Konski Cancer 2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 61

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemoptysis

bull Fig2 toux

733 689

812 802

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 62

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig3 doul thor 321 279

535 482

Cough

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 63

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 4 overall symptom burden

575 519

648 638

Thoracic pain

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 64

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 5 survie 1a

Cutoff (sensitivity analysis) BED[10] 35Gy vs LD

100 162

555 609

Overall symptom burden

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 65

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cutoff BED[10] 35Gy vs LD

265 217

Overall survival at 1y

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 66

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 7 Tox dysphagie

Cutoff BED[10] 30Gy vs LD

205 149

about x 2

Toxicity (dysphagia)

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 67

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomized trial 250 patients (Falk BMJ 2002)

bull Locally advanced non resectable NSCLC with minimal thoracic symptoms

bull Immediate vs delayed RT (at symptom onset)

bull In delayed arm 56 of patients died without RT

bull No difference in QOL odr OS

bull More acute toxicity in immediate RT arm

Randomized trial (Sundstrom Radiother Oncol 2005)

bull Advanced NSCLC

bull 2 RT schedules (5x4Gy vs 2x85 Gy) immediate RT

bull Stratification according to presenceabsence of thoracic symptoms

bull In asymptomatic patients no long term symptom control but important dysphagia

Timing

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 68

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull in 97 malignant

bull in 5-10 of lung cancer patients

bull Histology (exclude benign disease RT-chemosensible tumours

bull Generally spontanous improvement of symptoms by formation of collaterals

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 69

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Treatment

1 symptomatic

bull steroids

bull diuretics

bull Elevation of headthorax

2 causal bull chemotherapy (SCLC

lymphomas germinal tumours)

bull Endovascular stent placement

bull radiotherapy Palliative care in lung cancer ACCP

evidence- based clinical practice guidelines

(2nd edition)

Kvale Chest 2007

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 70

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

Radiotherapy

bull Mostly clinical response within 72 h

bull Complete clinical response at 2 w in 78 of patients with SCLC

and 63 of patients with NSCLC

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 71

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 72

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 73

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duhamel Atlas clinique des maladies

des voies aeacuteriennes Elsevier

wwwupmccancercenterscom

Endobronchial brachytherapy

Cochrane analysis (Cardona The Cochrane

Library 2008)

bull No improved

symptom relief by

addition of

endobronchial

brachytherapy to

EBRT

bull Indicated in selected

patients pretreated

by EBRT with

central

endobronchial

obstruction

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 74

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Ozkok Lung Cancer 2008

Endobronchial brachytherapy

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Take home lung cancer

Dosefractionation

bull Minimum 10x3 Gy 5xw or equivalent

ndash better symptom control and better overall survival

ndash But more toxicity

bull Short schedule for symptom control and limited toxicity

ndashPoor performance status limited life expectancy

Timing

bull RT at the moment of symptom onset

bull No place for bdquoprophylactic palliative RTldquo according to evidence based guidelines

ndashExceptions

bull Young patient good PS aim of local control

bull Imminent symptoms (superior vena cava syndrome central airway obstruction

Rodrigues Pract Rad Oncol 2011

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 80

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 82

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 83

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 84

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 90

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

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bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

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Scoccianti Radiother Oncol 2012

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SRO Tutorial Palliative Care ndash Palliative Radiotherapy 7

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Pain

ndashBone

ndashSoft tissue

bull Neurologic compression

ndashSpinal cord

ndashPeripheral nerves

ndashBrain

bull Haemorrhage

bull Symptoms caused by obstruction

ndashAirways dyspnoea

ndashSwallowing route dysphagia

ndashVenous flow superiorinferior cava syndrome

ndashUrinary tract urinary retention renal failure

bull Cosmesis odour in tumours infiltrating the skin

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 8

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz Cancer J 2010

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 9

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz Cancer J 2010

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 10

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Van Oorschot Sem Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 11

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 12

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cancer 2010

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 13

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastases

bull What tumours

bull Does RT work

bull Causal and symptomatic effect (anti-tumour anti-

inflammatory)

bull How do you treat them Why Studies on fractionation

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 14

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

RT of bone metastases -

fractionation

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 15

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lievens RO 2000

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 16

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lievens RO 2000

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 17

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Konski Semin Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 18

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Konski Semin Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 19

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Overall

response

rate

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 20

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Complete

response

rate

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 21

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Retreat

ment

rate

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 22

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull EBRT significant palliation of painful bone metastasis in

50-80 of patients complete pain relief in up to 13 of

patients (Chow JCO 2007)

bull Optimal fractionation RT technique combination with other

treatment options

bull Systematic review combined with expert opinions

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 23

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Uncomplicated bone

metastasis

Single vs multiple

fractions

bull Pain relief

equivalent

bull Long term toxicity

equivalent

bull Single fraction

optimal patient and

caregiver

convenience

bull Retreatment rate

20 vs 8

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 24

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Repeat treatment of painful spinal metastasis

bull Pain relief in 46-80

bull Cave dose to spinal cord

bull Dosefractionation unclear

bull Recommendation prospective trial

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 25

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Comparable fracture risk Chow Clin Oncol 2012

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 26

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Comparable risk of

spinal cord

compression

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 27

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SBRT of spinal metastasis

bull Mostly retrospective single-institution series

bull Recommendation prospective trial

bull Not primary treatment for spinal met causing spinal cord

compression

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 28

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Radionuclides

bull Important often underused option for multifocal bone

metastasis

bull For osteoblastic metastasis

bull Based on available data do not obviate need for EBRT

bull Recommendation prospective studies on prophylactic use

of radiopharmaceuticals in patients with limited bone

metastases combination with other systemic agents

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 29

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 30

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Biphosphonates

bull Several prospective studies on concurrent EBRT and

biphosphonates successful pain relief promotion of re-

ossification of damaged bone acceptable risk of toxicity

bull Not shown that combination better than EBRT alone for

pain relief

bull Recommendation prospective trial on optimum RT

fractionation EBRT versus radionuclides dose and

duration of biphosphonates and scheduling

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 31

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 32

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Denosumab

Lipton Curr Opp Supp Pall Care 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 33

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lipton Curr Opp Supp

Pall Care 2011

Denosumab versus

Zoledronate

Prevention of SREs (path fracture RT or OP to bone

spinal cord compression)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 34

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Breast

superior

Prostate

superior

Other solid

tumors or

multiple

myeloma

non inferior

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 35

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Vertebroplastykyphoplasty

bull No prospective data to suggest

that vertkyph obviates the

need for EBRT in painful bone

met

bull Small series of patients treated

by vertkyph plus EBRT

bull Recommendation prospective

trials on patient selection

efficacy toxicity and timing of

vertkyph and RT

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 36

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 37

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Non inferiority study

bull 272 patients randomized

Neuropathic pain

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 38

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 39

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 40

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Spinal cord compression

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 41

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 42

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 43

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Patchell Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 44

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

RT short versus

long course

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 45

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 46

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 47

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 48

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 49

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 50

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull SRO tutorial CNS PD Dr A Pica

bull ScocciantiRicardi Radiother Oncol 2012 Review

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 51

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemorrhage

bull Bleeding in 6-10 of patients with advanced

cancer (Pereira et al Topics in Palliative Care Vol 4 New York

Oxford University Press 2000)

bull haemoptysis

bull haematemesis

bull haematocheziamelaena

bull vaginal bleeding

bull haematuria

bull bleeding in ulcerated skin lesions

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 52

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Mechanisms of haemostatic radiotherapy

bull Sparse literature

bull Coagulation activationsup1

ndash Oxydative endothelial damage

ndash Activation of thrombocytes

ndash Activation of inflammation

bull Long term anti-angiogenetic

sup1 Hallahan et al Oncology (Huntingt) 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 53

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Prostate cancer

bull Reduction of pain and bleeding in hormone refractory

prostate cancer (Kynaston Br J Urol 1990 Kawakami Nippon

Hinyokika Gakkai Zasshi 1993 Kalapurakal Int J Radiat Oncol Biol Phys

2003)

bull 100 improvement in patients with important hematuria (Carlton J Urol 1972)

Bladder cancer (Srinivasan et al Clin Oncol (R Coll Radiol) 1994)

bull 17 Gy in 2 fractions3 days 59 clearance of hematuria

bull 45 Gy in 12 fractions26 days 16 clearance of

hematuria

bull Selection by performance status Palliation (pain and

hematuria) better with hypofractionated RT worse

survival

bull No important side effects

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 54

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung cancer

bull Control of hemoptysis in up to 80 of patients (Brundage

Can J Oncol 1996 Medical Research Council Lung Cancer Working Party

Br J Cancer 1992 Hoskin in Doyle et al Second Edition New York

Oxford University Press 1998 Langendijk Int J Radiat Oncol Biol Phys

2000)

bull Optimal dosefractionation

ndash Hypofractionated RT seems to be equally effective to multiple

fractions (Rees Clin Oncol (R Coll Radiol) 1997 Sundstrom JCO

2004 Phase III Stevens Australas Radiol 1995 Phase III studies of

the MRC (s above)

ndash 10 Gy Single fraction equally effective to multiple fractions less

toxic (Hoskin in Doyle et al Second Edition New York Oxford

University Press 1998 Medical Research Council Lung Cancer

Working Party Br J Cancer 1992)

ndash Mostly total dose of around 20 Gy (multiple fractions) or 8 Gy

single fraction recommended

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 55

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Van Lonkhuijzen

Radiother Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 56

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gynaecologic tumours

bull Cf review van Lonkhuijzen Radiother Oncol 2011

bull Consider intracavitary HDR brachytherapy

Rectal cancer

bull Up to 85 control of rectal bleeding (Hoskin in Doyle et al Second Edition New York Oxford University Press 1998)

Kaposi sarcoma

bull Good palliation for pain bleeding or edema TD 15-40 Gy SD 2 Gy gt90 response 70 complete remission (Review Becker et al Onkologie 2006)

Skin tumours (Miller in Doyle Oxford Textbook of Palliative Medicine New York Oxford University Press 1993)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 57

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duration of treatment effect

Lung cancer

bull Median duration of palliation 50 of remaining life span (30 Gy10d

27 Gy6d 17 Gy2 fract1w apart) (Medical Research Council Br J

Cancer 1991)

bull 1 fract 10 Gy vs 2 fract 85 Gy more patients need repeat RT (Medical Research Council Lung Cancer Working Party Br J Cancer 1992)

bull 417 pat need repeat RT within 3 m after 1x10 Gy (Scolaro Radiol

Med 1995)

Rec ovarian cancer

bull Median duration of palliation 4 m in 90 of patients until death (Corn Cancer 1994)

Cervical endometrial cancer

bull In 50 of patients pall Effect until death with 1-2x10 Gy

ndash Halle IJROBP 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 58

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull RT effective for improvement of

ndashThoracic symptoms (haemoptysis cough thoracic pain

dyspnoea airway obstruction) (Sirzeacuten Acta Oncol 2003 and others)

ndashQOL in about 13 of patients (Langendijk IJROBP 2000)

RT schedules

bull Systematic review (Fairchild JCO 264001-4011 2008)

ndash13 randomized trials 3473 patients

ndashdifferent RT schedules

ndashAim find optimal RT schedule for maximal palliation with

minimal toxicityneed for reirradiation

Thoracic symptoms

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 59

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz

Cancer

2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 60

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz Chow Hartsell Konski Cancer 2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 61

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemoptysis

bull Fig2 toux

733 689

812 802

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 62

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig3 doul thor 321 279

535 482

Cough

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 63

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 4 overall symptom burden

575 519

648 638

Thoracic pain

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 64

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 5 survie 1a

Cutoff (sensitivity analysis) BED[10] 35Gy vs LD

100 162

555 609

Overall symptom burden

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 65

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cutoff BED[10] 35Gy vs LD

265 217

Overall survival at 1y

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 66

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 7 Tox dysphagie

Cutoff BED[10] 30Gy vs LD

205 149

about x 2

Toxicity (dysphagia)

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 67

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomized trial 250 patients (Falk BMJ 2002)

bull Locally advanced non resectable NSCLC with minimal thoracic symptoms

bull Immediate vs delayed RT (at symptom onset)

bull In delayed arm 56 of patients died without RT

bull No difference in QOL odr OS

bull More acute toxicity in immediate RT arm

Randomized trial (Sundstrom Radiother Oncol 2005)

bull Advanced NSCLC

bull 2 RT schedules (5x4Gy vs 2x85 Gy) immediate RT

bull Stratification according to presenceabsence of thoracic symptoms

bull In asymptomatic patients no long term symptom control but important dysphagia

Timing

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 68

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull in 97 malignant

bull in 5-10 of lung cancer patients

bull Histology (exclude benign disease RT-chemosensible tumours

bull Generally spontanous improvement of symptoms by formation of collaterals

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 69

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Treatment

1 symptomatic

bull steroids

bull diuretics

bull Elevation of headthorax

2 causal bull chemotherapy (SCLC

lymphomas germinal tumours)

bull Endovascular stent placement

bull radiotherapy Palliative care in lung cancer ACCP

evidence- based clinical practice guidelines

(2nd edition)

Kvale Chest 2007

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 70

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

Radiotherapy

bull Mostly clinical response within 72 h

bull Complete clinical response at 2 w in 78 of patients with SCLC

and 63 of patients with NSCLC

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 71

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 72

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 73

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duhamel Atlas clinique des maladies

des voies aeacuteriennes Elsevier

wwwupmccancercenterscom

Endobronchial brachytherapy

Cochrane analysis (Cardona The Cochrane

Library 2008)

bull No improved

symptom relief by

addition of

endobronchial

brachytherapy to

EBRT

bull Indicated in selected

patients pretreated

by EBRT with

central

endobronchial

obstruction

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 74

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Ozkok Lung Cancer 2008

Endobronchial brachytherapy

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 75

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Take home lung cancer

Dosefractionation

bull Minimum 10x3 Gy 5xw or equivalent

ndash better symptom control and better overall survival

ndash But more toxicity

bull Short schedule for symptom control and limited toxicity

ndashPoor performance status limited life expectancy

Timing

bull RT at the moment of symptom onset

bull No place for bdquoprophylactic palliative RTldquo according to evidence based guidelines

ndashExceptions

bull Young patient good PS aim of local control

bull Imminent symptoms (superior vena cava syndrome central airway obstruction

Rodrigues Pract Rad Oncol 2011

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

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Homs Eur J CancerLancet 2004

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ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

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Randomisierte Studien

Homs Lancet 2004

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Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

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bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

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Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

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Scoccianti Radiother Oncol 2012

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Lutz Cancer J 2010

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Lutz Cancer J 2010

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Van Oorschot Sem Oncol 2011

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cancer 2010

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Bone metastases

bull What tumours

bull Does RT work

bull Causal and symptomatic effect (anti-tumour anti-

inflammatory)

bull How do you treat them Why Studies on fractionation

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RT of bone metastases -

fractionation

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Lievens RO 2000

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Lievens RO 2000

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Konski Semin Oncol 2005

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Konski Semin Oncol 2005

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Overall

response

rate

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Chow Clin Oncol 2012

Complete

response

rate

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Chow Clin Oncol 2012

Retreat

ment

rate

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull EBRT significant palliation of painful bone metastasis in

50-80 of patients complete pain relief in up to 13 of

patients (Chow JCO 2007)

bull Optimal fractionation RT technique combination with other

treatment options

bull Systematic review combined with expert opinions

Lutz IJROBP 2011

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Uncomplicated bone

metastasis

Single vs multiple

fractions

bull Pain relief

equivalent

bull Long term toxicity

equivalent

bull Single fraction

optimal patient and

caregiver

convenience

bull Retreatment rate

20 vs 8

Lutz IJROBP 2011

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Repeat treatment of painful spinal metastasis

bull Pain relief in 46-80

bull Cave dose to spinal cord

bull Dosefractionation unclear

bull Recommendation prospective trial

Lutz IJROBP 2011

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Comparable fracture risk Chow Clin Oncol 2012

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Comparable risk of

spinal cord

compression

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SBRT of spinal metastasis

bull Mostly retrospective single-institution series

bull Recommendation prospective trial

bull Not primary treatment for spinal met causing spinal cord

compression

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 28

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Radionuclides

bull Important often underused option for multifocal bone

metastasis

bull For osteoblastic metastasis

bull Based on available data do not obviate need for EBRT

bull Recommendation prospective studies on prophylactic use

of radiopharmaceuticals in patients with limited bone

metastases combination with other systemic agents

Lutz IJROBP 2011

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Biphosphonates

bull Several prospective studies on concurrent EBRT and

biphosphonates successful pain relief promotion of re-

ossification of damaged bone acceptable risk of toxicity

bull Not shown that combination better than EBRT alone for

pain relief

bull Recommendation prospective trial on optimum RT

fractionation EBRT versus radionuclides dose and

duration of biphosphonates and scheduling

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 31

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 32

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Denosumab

Lipton Curr Opp Supp Pall Care 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 33

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lipton Curr Opp Supp

Pall Care 2011

Denosumab versus

Zoledronate

Prevention of SREs (path fracture RT or OP to bone

spinal cord compression)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 34

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Breast

superior

Prostate

superior

Other solid

tumors or

multiple

myeloma

non inferior

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 35

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Vertebroplastykyphoplasty

bull No prospective data to suggest

that vertkyph obviates the

need for EBRT in painful bone

met

bull Small series of patients treated

by vertkyph plus EBRT

bull Recommendation prospective

trials on patient selection

efficacy toxicity and timing of

vertkyph and RT

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 36

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 37

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Non inferiority study

bull 272 patients randomized

Neuropathic pain

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 38

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 39

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 40

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Spinal cord compression

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 41

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 42

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 43

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Patchell Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 44

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

RT short versus

long course

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 45

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 46

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 47

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 48

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 49

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 50

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull SRO tutorial CNS PD Dr A Pica

bull ScocciantiRicardi Radiother Oncol 2012 Review

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 51

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemorrhage

bull Bleeding in 6-10 of patients with advanced

cancer (Pereira et al Topics in Palliative Care Vol 4 New York

Oxford University Press 2000)

bull haemoptysis

bull haematemesis

bull haematocheziamelaena

bull vaginal bleeding

bull haematuria

bull bleeding in ulcerated skin lesions

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 52

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Mechanisms of haemostatic radiotherapy

bull Sparse literature

bull Coagulation activationsup1

ndash Oxydative endothelial damage

ndash Activation of thrombocytes

ndash Activation of inflammation

bull Long term anti-angiogenetic

sup1 Hallahan et al Oncology (Huntingt) 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 53

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Prostate cancer

bull Reduction of pain and bleeding in hormone refractory

prostate cancer (Kynaston Br J Urol 1990 Kawakami Nippon

Hinyokika Gakkai Zasshi 1993 Kalapurakal Int J Radiat Oncol Biol Phys

2003)

bull 100 improvement in patients with important hematuria (Carlton J Urol 1972)

Bladder cancer (Srinivasan et al Clin Oncol (R Coll Radiol) 1994)

bull 17 Gy in 2 fractions3 days 59 clearance of hematuria

bull 45 Gy in 12 fractions26 days 16 clearance of

hematuria

bull Selection by performance status Palliation (pain and

hematuria) better with hypofractionated RT worse

survival

bull No important side effects

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 54

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung cancer

bull Control of hemoptysis in up to 80 of patients (Brundage

Can J Oncol 1996 Medical Research Council Lung Cancer Working Party

Br J Cancer 1992 Hoskin in Doyle et al Second Edition New York

Oxford University Press 1998 Langendijk Int J Radiat Oncol Biol Phys

2000)

bull Optimal dosefractionation

ndash Hypofractionated RT seems to be equally effective to multiple

fractions (Rees Clin Oncol (R Coll Radiol) 1997 Sundstrom JCO

2004 Phase III Stevens Australas Radiol 1995 Phase III studies of

the MRC (s above)

ndash 10 Gy Single fraction equally effective to multiple fractions less

toxic (Hoskin in Doyle et al Second Edition New York Oxford

University Press 1998 Medical Research Council Lung Cancer

Working Party Br J Cancer 1992)

ndash Mostly total dose of around 20 Gy (multiple fractions) or 8 Gy

single fraction recommended

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 55

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Van Lonkhuijzen

Radiother Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 56

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gynaecologic tumours

bull Cf review van Lonkhuijzen Radiother Oncol 2011

bull Consider intracavitary HDR brachytherapy

Rectal cancer

bull Up to 85 control of rectal bleeding (Hoskin in Doyle et al Second Edition New York Oxford University Press 1998)

Kaposi sarcoma

bull Good palliation for pain bleeding or edema TD 15-40 Gy SD 2 Gy gt90 response 70 complete remission (Review Becker et al Onkologie 2006)

Skin tumours (Miller in Doyle Oxford Textbook of Palliative Medicine New York Oxford University Press 1993)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 57

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duration of treatment effect

Lung cancer

bull Median duration of palliation 50 of remaining life span (30 Gy10d

27 Gy6d 17 Gy2 fract1w apart) (Medical Research Council Br J

Cancer 1991)

bull 1 fract 10 Gy vs 2 fract 85 Gy more patients need repeat RT (Medical Research Council Lung Cancer Working Party Br J Cancer 1992)

bull 417 pat need repeat RT within 3 m after 1x10 Gy (Scolaro Radiol

Med 1995)

Rec ovarian cancer

bull Median duration of palliation 4 m in 90 of patients until death (Corn Cancer 1994)

Cervical endometrial cancer

bull In 50 of patients pall Effect until death with 1-2x10 Gy

ndash Halle IJROBP 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 58

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull RT effective for improvement of

ndashThoracic symptoms (haemoptysis cough thoracic pain

dyspnoea airway obstruction) (Sirzeacuten Acta Oncol 2003 and others)

ndashQOL in about 13 of patients (Langendijk IJROBP 2000)

RT schedules

bull Systematic review (Fairchild JCO 264001-4011 2008)

ndash13 randomized trials 3473 patients

ndashdifferent RT schedules

ndashAim find optimal RT schedule for maximal palliation with

minimal toxicityneed for reirradiation

Thoracic symptoms

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 59

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz

Cancer

2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 60

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz Chow Hartsell Konski Cancer 2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 61

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemoptysis

bull Fig2 toux

733 689

812 802

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 62

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig3 doul thor 321 279

535 482

Cough

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 63

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 4 overall symptom burden

575 519

648 638

Thoracic pain

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 64

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 5 survie 1a

Cutoff (sensitivity analysis) BED[10] 35Gy vs LD

100 162

555 609

Overall symptom burden

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 65

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cutoff BED[10] 35Gy vs LD

265 217

Overall survival at 1y

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 66

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 7 Tox dysphagie

Cutoff BED[10] 30Gy vs LD

205 149

about x 2

Toxicity (dysphagia)

Fairchild JCO 2008

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomized trial 250 patients (Falk BMJ 2002)

bull Locally advanced non resectable NSCLC with minimal thoracic symptoms

bull Immediate vs delayed RT (at symptom onset)

bull In delayed arm 56 of patients died without RT

bull No difference in QOL odr OS

bull More acute toxicity in immediate RT arm

Randomized trial (Sundstrom Radiother Oncol 2005)

bull Advanced NSCLC

bull 2 RT schedules (5x4Gy vs 2x85 Gy) immediate RT

bull Stratification according to presenceabsence of thoracic symptoms

bull In asymptomatic patients no long term symptom control but important dysphagia

Timing

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull in 97 malignant

bull in 5-10 of lung cancer patients

bull Histology (exclude benign disease RT-chemosensible tumours

bull Generally spontanous improvement of symptoms by formation of collaterals

Superior vena cava syndrome

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Treatment

1 symptomatic

bull steroids

bull diuretics

bull Elevation of headthorax

2 causal bull chemotherapy (SCLC

lymphomas germinal tumours)

bull Endovascular stent placement

bull radiotherapy Palliative care in lung cancer ACCP

evidence- based clinical practice guidelines

(2nd edition)

Kvale Chest 2007

Superior vena cava syndrome

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

Radiotherapy

bull Mostly clinical response within 72 h

bull Complete clinical response at 2 w in 78 of patients with SCLC

and 63 of patients with NSCLC

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duhamel Atlas clinique des maladies

des voies aeacuteriennes Elsevier

wwwupmccancercenterscom

Endobronchial brachytherapy

Cochrane analysis (Cardona The Cochrane

Library 2008)

bull No improved

symptom relief by

addition of

endobronchial

brachytherapy to

EBRT

bull Indicated in selected

patients pretreated

by EBRT with

central

endobronchial

obstruction

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Ozkok Lung Cancer 2008

Endobronchial brachytherapy

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Take home lung cancer

Dosefractionation

bull Minimum 10x3 Gy 5xw or equivalent

ndash better symptom control and better overall survival

ndash But more toxicity

bull Short schedule for symptom control and limited toxicity

ndashPoor performance status limited life expectancy

Timing

bull RT at the moment of symptom onset

bull No place for bdquoprophylactic palliative RTldquo according to evidence based guidelines

ndashExceptions

bull Young patient good PS aim of local control

bull Imminent symptoms (superior vena cava syndrome central airway obstruction

Rodrigues Pract Rad Oncol 2011

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

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Homs Eur J CancerLancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

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Randomisierte Studien

Homs Lancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

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Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

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Scoccianti Radiother Oncol 2012

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Page 9: SRO Tutorial Palliative Care 04.05.2012 Palliative Radiotherapy · 2018-02-22 · SRO Tutorial Palliative Care – Palliative Radiotherapy 30 Jacqueline Vock, Universitätsklinik

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz Cancer J 2010

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Van Oorschot Sem Oncol 2011

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cancer 2010

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 13

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastases

bull What tumours

bull Does RT work

bull Causal and symptomatic effect (anti-tumour anti-

inflammatory)

bull How do you treat them Why Studies on fractionation

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

RT of bone metastases -

fractionation

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lievens RO 2000

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lievens RO 2000

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Konski Semin Oncol 2005

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Konski Semin Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 19

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Overall

response

rate

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Complete

response

rate

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Retreat

ment

rate

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull EBRT significant palliation of painful bone metastasis in

50-80 of patients complete pain relief in up to 13 of

patients (Chow JCO 2007)

bull Optimal fractionation RT technique combination with other

treatment options

bull Systematic review combined with expert opinions

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 23

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Uncomplicated bone

metastasis

Single vs multiple

fractions

bull Pain relief

equivalent

bull Long term toxicity

equivalent

bull Single fraction

optimal patient and

caregiver

convenience

bull Retreatment rate

20 vs 8

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 24

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Repeat treatment of painful spinal metastasis

bull Pain relief in 46-80

bull Cave dose to spinal cord

bull Dosefractionation unclear

bull Recommendation prospective trial

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 25

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Comparable fracture risk Chow Clin Oncol 2012

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 26

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Comparable risk of

spinal cord

compression

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 27

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SBRT of spinal metastasis

bull Mostly retrospective single-institution series

bull Recommendation prospective trial

bull Not primary treatment for spinal met causing spinal cord

compression

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 28

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Radionuclides

bull Important often underused option for multifocal bone

metastasis

bull For osteoblastic metastasis

bull Based on available data do not obviate need for EBRT

bull Recommendation prospective studies on prophylactic use

of radiopharmaceuticals in patients with limited bone

metastases combination with other systemic agents

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 29

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 30

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Biphosphonates

bull Several prospective studies on concurrent EBRT and

biphosphonates successful pain relief promotion of re-

ossification of damaged bone acceptable risk of toxicity

bull Not shown that combination better than EBRT alone for

pain relief

bull Recommendation prospective trial on optimum RT

fractionation EBRT versus radionuclides dose and

duration of biphosphonates and scheduling

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 31

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 32

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Denosumab

Lipton Curr Opp Supp Pall Care 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 33

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lipton Curr Opp Supp

Pall Care 2011

Denosumab versus

Zoledronate

Prevention of SREs (path fracture RT or OP to bone

spinal cord compression)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 34

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Breast

superior

Prostate

superior

Other solid

tumors or

multiple

myeloma

non inferior

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 35

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Vertebroplastykyphoplasty

bull No prospective data to suggest

that vertkyph obviates the

need for EBRT in painful bone

met

bull Small series of patients treated

by vertkyph plus EBRT

bull Recommendation prospective

trials on patient selection

efficacy toxicity and timing of

vertkyph and RT

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 36

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 37

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Non inferiority study

bull 272 patients randomized

Neuropathic pain

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 38

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 39

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 40

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Spinal cord compression

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 41

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 42

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 43

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Patchell Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 44

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

RT short versus

long course

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 45

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 46

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 47

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 48

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 49

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 50

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull SRO tutorial CNS PD Dr A Pica

bull ScocciantiRicardi Radiother Oncol 2012 Review

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 51

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemorrhage

bull Bleeding in 6-10 of patients with advanced

cancer (Pereira et al Topics in Palliative Care Vol 4 New York

Oxford University Press 2000)

bull haemoptysis

bull haematemesis

bull haematocheziamelaena

bull vaginal bleeding

bull haematuria

bull bleeding in ulcerated skin lesions

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 52

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Mechanisms of haemostatic radiotherapy

bull Sparse literature

bull Coagulation activationsup1

ndash Oxydative endothelial damage

ndash Activation of thrombocytes

ndash Activation of inflammation

bull Long term anti-angiogenetic

sup1 Hallahan et al Oncology (Huntingt) 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 53

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Prostate cancer

bull Reduction of pain and bleeding in hormone refractory

prostate cancer (Kynaston Br J Urol 1990 Kawakami Nippon

Hinyokika Gakkai Zasshi 1993 Kalapurakal Int J Radiat Oncol Biol Phys

2003)

bull 100 improvement in patients with important hematuria (Carlton J Urol 1972)

Bladder cancer (Srinivasan et al Clin Oncol (R Coll Radiol) 1994)

bull 17 Gy in 2 fractions3 days 59 clearance of hematuria

bull 45 Gy in 12 fractions26 days 16 clearance of

hematuria

bull Selection by performance status Palliation (pain and

hematuria) better with hypofractionated RT worse

survival

bull No important side effects

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 54

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung cancer

bull Control of hemoptysis in up to 80 of patients (Brundage

Can J Oncol 1996 Medical Research Council Lung Cancer Working Party

Br J Cancer 1992 Hoskin in Doyle et al Second Edition New York

Oxford University Press 1998 Langendijk Int J Radiat Oncol Biol Phys

2000)

bull Optimal dosefractionation

ndash Hypofractionated RT seems to be equally effective to multiple

fractions (Rees Clin Oncol (R Coll Radiol) 1997 Sundstrom JCO

2004 Phase III Stevens Australas Radiol 1995 Phase III studies of

the MRC (s above)

ndash 10 Gy Single fraction equally effective to multiple fractions less

toxic (Hoskin in Doyle et al Second Edition New York Oxford

University Press 1998 Medical Research Council Lung Cancer

Working Party Br J Cancer 1992)

ndash Mostly total dose of around 20 Gy (multiple fractions) or 8 Gy

single fraction recommended

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 55

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Van Lonkhuijzen

Radiother Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 56

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gynaecologic tumours

bull Cf review van Lonkhuijzen Radiother Oncol 2011

bull Consider intracavitary HDR brachytherapy

Rectal cancer

bull Up to 85 control of rectal bleeding (Hoskin in Doyle et al Second Edition New York Oxford University Press 1998)

Kaposi sarcoma

bull Good palliation for pain bleeding or edema TD 15-40 Gy SD 2 Gy gt90 response 70 complete remission (Review Becker et al Onkologie 2006)

Skin tumours (Miller in Doyle Oxford Textbook of Palliative Medicine New York Oxford University Press 1993)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 57

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duration of treatment effect

Lung cancer

bull Median duration of palliation 50 of remaining life span (30 Gy10d

27 Gy6d 17 Gy2 fract1w apart) (Medical Research Council Br J

Cancer 1991)

bull 1 fract 10 Gy vs 2 fract 85 Gy more patients need repeat RT (Medical Research Council Lung Cancer Working Party Br J Cancer 1992)

bull 417 pat need repeat RT within 3 m after 1x10 Gy (Scolaro Radiol

Med 1995)

Rec ovarian cancer

bull Median duration of palliation 4 m in 90 of patients until death (Corn Cancer 1994)

Cervical endometrial cancer

bull In 50 of patients pall Effect until death with 1-2x10 Gy

ndash Halle IJROBP 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 58

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull RT effective for improvement of

ndashThoracic symptoms (haemoptysis cough thoracic pain

dyspnoea airway obstruction) (Sirzeacuten Acta Oncol 2003 and others)

ndashQOL in about 13 of patients (Langendijk IJROBP 2000)

RT schedules

bull Systematic review (Fairchild JCO 264001-4011 2008)

ndash13 randomized trials 3473 patients

ndashdifferent RT schedules

ndashAim find optimal RT schedule for maximal palliation with

minimal toxicityneed for reirradiation

Thoracic symptoms

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 59

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz

Cancer

2007

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz Chow Hartsell Konski Cancer 2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 61

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemoptysis

bull Fig2 toux

733 689

812 802

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 62

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig3 doul thor 321 279

535 482

Cough

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 63

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 4 overall symptom burden

575 519

648 638

Thoracic pain

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 64

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 5 survie 1a

Cutoff (sensitivity analysis) BED[10] 35Gy vs LD

100 162

555 609

Overall symptom burden

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 65

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cutoff BED[10] 35Gy vs LD

265 217

Overall survival at 1y

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 66

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 7 Tox dysphagie

Cutoff BED[10] 30Gy vs LD

205 149

about x 2

Toxicity (dysphagia)

Fairchild JCO 2008

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomized trial 250 patients (Falk BMJ 2002)

bull Locally advanced non resectable NSCLC with minimal thoracic symptoms

bull Immediate vs delayed RT (at symptom onset)

bull In delayed arm 56 of patients died without RT

bull No difference in QOL odr OS

bull More acute toxicity in immediate RT arm

Randomized trial (Sundstrom Radiother Oncol 2005)

bull Advanced NSCLC

bull 2 RT schedules (5x4Gy vs 2x85 Gy) immediate RT

bull Stratification according to presenceabsence of thoracic symptoms

bull In asymptomatic patients no long term symptom control but important dysphagia

Timing

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull in 97 malignant

bull in 5-10 of lung cancer patients

bull Histology (exclude benign disease RT-chemosensible tumours

bull Generally spontanous improvement of symptoms by formation of collaterals

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 69

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Treatment

1 symptomatic

bull steroids

bull diuretics

bull Elevation of headthorax

2 causal bull chemotherapy (SCLC

lymphomas germinal tumours)

bull Endovascular stent placement

bull radiotherapy Palliative care in lung cancer ACCP

evidence- based clinical practice guidelines

(2nd edition)

Kvale Chest 2007

Superior vena cava syndrome

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

Radiotherapy

bull Mostly clinical response within 72 h

bull Complete clinical response at 2 w in 78 of patients with SCLC

and 63 of patients with NSCLC

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duhamel Atlas clinique des maladies

des voies aeacuteriennes Elsevier

wwwupmccancercenterscom

Endobronchial brachytherapy

Cochrane analysis (Cardona The Cochrane

Library 2008)

bull No improved

symptom relief by

addition of

endobronchial

brachytherapy to

EBRT

bull Indicated in selected

patients pretreated

by EBRT with

central

endobronchial

obstruction

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Ozkok Lung Cancer 2008

Endobronchial brachytherapy

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Take home lung cancer

Dosefractionation

bull Minimum 10x3 Gy 5xw or equivalent

ndash better symptom control and better overall survival

ndash But more toxicity

bull Short schedule for symptom control and limited toxicity

ndashPoor performance status limited life expectancy

Timing

bull RT at the moment of symptom onset

bull No place for bdquoprophylactic palliative RTldquo according to evidence based guidelines

ndashExceptions

bull Young patient good PS aim of local control

bull Imminent symptoms (superior vena cava syndrome central airway obstruction

Rodrigues Pract Rad Oncol 2011

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 80

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

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Homs Eur J CancerLancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

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Randomisierte Studien

Homs Lancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

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Scoccianti Radiother Oncol 2012

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SRO Tutorial Palliative Care ndash Palliative Radiotherapy 102

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Page 10: SRO Tutorial Palliative Care 04.05.2012 Palliative Radiotherapy · 2018-02-22 · SRO Tutorial Palliative Care – Palliative Radiotherapy 30 Jacqueline Vock, Universitätsklinik

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Van Oorschot Sem Oncol 2011

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cancer 2010

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 13

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastases

bull What tumours

bull Does RT work

bull Causal and symptomatic effect (anti-tumour anti-

inflammatory)

bull How do you treat them Why Studies on fractionation

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

RT of bone metastases -

fractionation

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lievens RO 2000

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lievens RO 2000

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Konski Semin Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 18

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Konski Semin Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 19

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Overall

response

rate

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Complete

response

rate

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 21

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Retreat

ment

rate

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 22

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull EBRT significant palliation of painful bone metastasis in

50-80 of patients complete pain relief in up to 13 of

patients (Chow JCO 2007)

bull Optimal fractionation RT technique combination with other

treatment options

bull Systematic review combined with expert opinions

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 23

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Uncomplicated bone

metastasis

Single vs multiple

fractions

bull Pain relief

equivalent

bull Long term toxicity

equivalent

bull Single fraction

optimal patient and

caregiver

convenience

bull Retreatment rate

20 vs 8

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 24

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Repeat treatment of painful spinal metastasis

bull Pain relief in 46-80

bull Cave dose to spinal cord

bull Dosefractionation unclear

bull Recommendation prospective trial

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 25

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Comparable fracture risk Chow Clin Oncol 2012

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 26

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Comparable risk of

spinal cord

compression

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 27

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SBRT of spinal metastasis

bull Mostly retrospective single-institution series

bull Recommendation prospective trial

bull Not primary treatment for spinal met causing spinal cord

compression

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 28

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Radionuclides

bull Important often underused option for multifocal bone

metastasis

bull For osteoblastic metastasis

bull Based on available data do not obviate need for EBRT

bull Recommendation prospective studies on prophylactic use

of radiopharmaceuticals in patients with limited bone

metastases combination with other systemic agents

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 29

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 30

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Biphosphonates

bull Several prospective studies on concurrent EBRT and

biphosphonates successful pain relief promotion of re-

ossification of damaged bone acceptable risk of toxicity

bull Not shown that combination better than EBRT alone for

pain relief

bull Recommendation prospective trial on optimum RT

fractionation EBRT versus radionuclides dose and

duration of biphosphonates and scheduling

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 31

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 32

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Denosumab

Lipton Curr Opp Supp Pall Care 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 33

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lipton Curr Opp Supp

Pall Care 2011

Denosumab versus

Zoledronate

Prevention of SREs (path fracture RT or OP to bone

spinal cord compression)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 34

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Breast

superior

Prostate

superior

Other solid

tumors or

multiple

myeloma

non inferior

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 35

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Vertebroplastykyphoplasty

bull No prospective data to suggest

that vertkyph obviates the

need for EBRT in painful bone

met

bull Small series of patients treated

by vertkyph plus EBRT

bull Recommendation prospective

trials on patient selection

efficacy toxicity and timing of

vertkyph and RT

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 36

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 37

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Non inferiority study

bull 272 patients randomized

Neuropathic pain

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 38

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 39

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 40

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Spinal cord compression

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 41

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 42

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 43

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Patchell Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 44

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

RT short versus

long course

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 45

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 46

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 47

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 48

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 49

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 50

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull SRO tutorial CNS PD Dr A Pica

bull ScocciantiRicardi Radiother Oncol 2012 Review

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 51

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemorrhage

bull Bleeding in 6-10 of patients with advanced

cancer (Pereira et al Topics in Palliative Care Vol 4 New York

Oxford University Press 2000)

bull haemoptysis

bull haematemesis

bull haematocheziamelaena

bull vaginal bleeding

bull haematuria

bull bleeding in ulcerated skin lesions

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 52

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Mechanisms of haemostatic radiotherapy

bull Sparse literature

bull Coagulation activationsup1

ndash Oxydative endothelial damage

ndash Activation of thrombocytes

ndash Activation of inflammation

bull Long term anti-angiogenetic

sup1 Hallahan et al Oncology (Huntingt) 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 53

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Prostate cancer

bull Reduction of pain and bleeding in hormone refractory

prostate cancer (Kynaston Br J Urol 1990 Kawakami Nippon

Hinyokika Gakkai Zasshi 1993 Kalapurakal Int J Radiat Oncol Biol Phys

2003)

bull 100 improvement in patients with important hematuria (Carlton J Urol 1972)

Bladder cancer (Srinivasan et al Clin Oncol (R Coll Radiol) 1994)

bull 17 Gy in 2 fractions3 days 59 clearance of hematuria

bull 45 Gy in 12 fractions26 days 16 clearance of

hematuria

bull Selection by performance status Palliation (pain and

hematuria) better with hypofractionated RT worse

survival

bull No important side effects

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 54

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung cancer

bull Control of hemoptysis in up to 80 of patients (Brundage

Can J Oncol 1996 Medical Research Council Lung Cancer Working Party

Br J Cancer 1992 Hoskin in Doyle et al Second Edition New York

Oxford University Press 1998 Langendijk Int J Radiat Oncol Biol Phys

2000)

bull Optimal dosefractionation

ndash Hypofractionated RT seems to be equally effective to multiple

fractions (Rees Clin Oncol (R Coll Radiol) 1997 Sundstrom JCO

2004 Phase III Stevens Australas Radiol 1995 Phase III studies of

the MRC (s above)

ndash 10 Gy Single fraction equally effective to multiple fractions less

toxic (Hoskin in Doyle et al Second Edition New York Oxford

University Press 1998 Medical Research Council Lung Cancer

Working Party Br J Cancer 1992)

ndash Mostly total dose of around 20 Gy (multiple fractions) or 8 Gy

single fraction recommended

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 55

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Van Lonkhuijzen

Radiother Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 56

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Gynaecologic tumours

bull Cf review van Lonkhuijzen Radiother Oncol 2011

bull Consider intracavitary HDR brachytherapy

Rectal cancer

bull Up to 85 control of rectal bleeding (Hoskin in Doyle et al Second Edition New York Oxford University Press 1998)

Kaposi sarcoma

bull Good palliation for pain bleeding or edema TD 15-40 Gy SD 2 Gy gt90 response 70 complete remission (Review Becker et al Onkologie 2006)

Skin tumours (Miller in Doyle Oxford Textbook of Palliative Medicine New York Oxford University Press 1993)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 57

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duration of treatment effect

Lung cancer

bull Median duration of palliation 50 of remaining life span (30 Gy10d

27 Gy6d 17 Gy2 fract1w apart) (Medical Research Council Br J

Cancer 1991)

bull 1 fract 10 Gy vs 2 fract 85 Gy more patients need repeat RT (Medical Research Council Lung Cancer Working Party Br J Cancer 1992)

bull 417 pat need repeat RT within 3 m after 1x10 Gy (Scolaro Radiol

Med 1995)

Rec ovarian cancer

bull Median duration of palliation 4 m in 90 of patients until death (Corn Cancer 1994)

Cervical endometrial cancer

bull In 50 of patients pall Effect until death with 1-2x10 Gy

ndash Halle IJROBP 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 58

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull RT effective for improvement of

ndashThoracic symptoms (haemoptysis cough thoracic pain

dyspnoea airway obstruction) (Sirzeacuten Acta Oncol 2003 and others)

ndashQOL in about 13 of patients (Langendijk IJROBP 2000)

RT schedules

bull Systematic review (Fairchild JCO 264001-4011 2008)

ndash13 randomized trials 3473 patients

ndashdifferent RT schedules

ndashAim find optimal RT schedule for maximal palliation with

minimal toxicityneed for reirradiation

Thoracic symptoms

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 59

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz

Cancer

2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 60

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz Chow Hartsell Konski Cancer 2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 61

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemoptysis

bull Fig2 toux

733 689

812 802

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 62

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig3 doul thor 321 279

535 482

Cough

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 63

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 4 overall symptom burden

575 519

648 638

Thoracic pain

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 64

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 5 survie 1a

Cutoff (sensitivity analysis) BED[10] 35Gy vs LD

100 162

555 609

Overall symptom burden

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 65

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cutoff BED[10] 35Gy vs LD

265 217

Overall survival at 1y

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 66

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 7 Tox dysphagie

Cutoff BED[10] 30Gy vs LD

205 149

about x 2

Toxicity (dysphagia)

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 67

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomized trial 250 patients (Falk BMJ 2002)

bull Locally advanced non resectable NSCLC with minimal thoracic symptoms

bull Immediate vs delayed RT (at symptom onset)

bull In delayed arm 56 of patients died without RT

bull No difference in QOL odr OS

bull More acute toxicity in immediate RT arm

Randomized trial (Sundstrom Radiother Oncol 2005)

bull Advanced NSCLC

bull 2 RT schedules (5x4Gy vs 2x85 Gy) immediate RT

bull Stratification according to presenceabsence of thoracic symptoms

bull In asymptomatic patients no long term symptom control but important dysphagia

Timing

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull in 97 malignant

bull in 5-10 of lung cancer patients

bull Histology (exclude benign disease RT-chemosensible tumours

bull Generally spontanous improvement of symptoms by formation of collaterals

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 69

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Treatment

1 symptomatic

bull steroids

bull diuretics

bull Elevation of headthorax

2 causal bull chemotherapy (SCLC

lymphomas germinal tumours)

bull Endovascular stent placement

bull radiotherapy Palliative care in lung cancer ACCP

evidence- based clinical practice guidelines

(2nd edition)

Kvale Chest 2007

Superior vena cava syndrome

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

Radiotherapy

bull Mostly clinical response within 72 h

bull Complete clinical response at 2 w in 78 of patients with SCLC

and 63 of patients with NSCLC

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 72

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 73

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duhamel Atlas clinique des maladies

des voies aeacuteriennes Elsevier

wwwupmccancercenterscom

Endobronchial brachytherapy

Cochrane analysis (Cardona The Cochrane

Library 2008)

bull No improved

symptom relief by

addition of

endobronchial

brachytherapy to

EBRT

bull Indicated in selected

patients pretreated

by EBRT with

central

endobronchial

obstruction

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 74

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Ozkok Lung Cancer 2008

Endobronchial brachytherapy

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Take home lung cancer

Dosefractionation

bull Minimum 10x3 Gy 5xw or equivalent

ndash better symptom control and better overall survival

ndash But more toxicity

bull Short schedule for symptom control and limited toxicity

ndashPoor performance status limited life expectancy

Timing

bull RT at the moment of symptom onset

bull No place for bdquoprophylactic palliative RTldquo according to evidence based guidelines

ndashExceptions

bull Young patient good PS aim of local control

bull Imminent symptoms (superior vena cava syndrome central airway obstruction

Rodrigues Pract Rad Oncol 2011

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 80

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

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Homs Eur J CancerLancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

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Randomisierte Studien

Homs Lancet 2004

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Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

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Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

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Scoccianti Radiother Oncol 2012

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SRO Tutorial Palliative Care ndash Palliative Radiotherapy 102

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cancer 2010

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 13

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastases

bull What tumours

bull Does RT work

bull Causal and symptomatic effect (anti-tumour anti-

inflammatory)

bull How do you treat them Why Studies on fractionation

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 14

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

RT of bone metastases -

fractionation

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 15

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lievens RO 2000

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lievens RO 2000

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Konski Semin Oncol 2005

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Konski Semin Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 19

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Overall

response

rate

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Complete

response

rate

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Retreat

ment

rate

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 22

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull EBRT significant palliation of painful bone metastasis in

50-80 of patients complete pain relief in up to 13 of

patients (Chow JCO 2007)

bull Optimal fractionation RT technique combination with other

treatment options

bull Systematic review combined with expert opinions

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 23

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Uncomplicated bone

metastasis

Single vs multiple

fractions

bull Pain relief

equivalent

bull Long term toxicity

equivalent

bull Single fraction

optimal patient and

caregiver

convenience

bull Retreatment rate

20 vs 8

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 24

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Repeat treatment of painful spinal metastasis

bull Pain relief in 46-80

bull Cave dose to spinal cord

bull Dosefractionation unclear

bull Recommendation prospective trial

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 25

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Comparable fracture risk Chow Clin Oncol 2012

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 26

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Comparable risk of

spinal cord

compression

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 27

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SBRT of spinal metastasis

bull Mostly retrospective single-institution series

bull Recommendation prospective trial

bull Not primary treatment for spinal met causing spinal cord

compression

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 28

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Radionuclides

bull Important often underused option for multifocal bone

metastasis

bull For osteoblastic metastasis

bull Based on available data do not obviate need for EBRT

bull Recommendation prospective studies on prophylactic use

of radiopharmaceuticals in patients with limited bone

metastases combination with other systemic agents

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 29

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 30

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Biphosphonates

bull Several prospective studies on concurrent EBRT and

biphosphonates successful pain relief promotion of re-

ossification of damaged bone acceptable risk of toxicity

bull Not shown that combination better than EBRT alone for

pain relief

bull Recommendation prospective trial on optimum RT

fractionation EBRT versus radionuclides dose and

duration of biphosphonates and scheduling

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 31

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 32

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Denosumab

Lipton Curr Opp Supp Pall Care 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 33

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lipton Curr Opp Supp

Pall Care 2011

Denosumab versus

Zoledronate

Prevention of SREs (path fracture RT or OP to bone

spinal cord compression)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 34

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Breast

superior

Prostate

superior

Other solid

tumors or

multiple

myeloma

non inferior

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 35

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Vertebroplastykyphoplasty

bull No prospective data to suggest

that vertkyph obviates the

need for EBRT in painful bone

met

bull Small series of patients treated

by vertkyph plus EBRT

bull Recommendation prospective

trials on patient selection

efficacy toxicity and timing of

vertkyph and RT

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 36

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 37

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Non inferiority study

bull 272 patients randomized

Neuropathic pain

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 38

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 39

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 40

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Spinal cord compression

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 41

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 42

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 43

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Patchell Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 44

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

RT short versus

long course

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 45

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 46

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 47

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 48

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 49

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 50

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull SRO tutorial CNS PD Dr A Pica

bull ScocciantiRicardi Radiother Oncol 2012 Review

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 51

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemorrhage

bull Bleeding in 6-10 of patients with advanced

cancer (Pereira et al Topics in Palliative Care Vol 4 New York

Oxford University Press 2000)

bull haemoptysis

bull haematemesis

bull haematocheziamelaena

bull vaginal bleeding

bull haematuria

bull bleeding in ulcerated skin lesions

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 52

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Mechanisms of haemostatic radiotherapy

bull Sparse literature

bull Coagulation activationsup1

ndash Oxydative endothelial damage

ndash Activation of thrombocytes

ndash Activation of inflammation

bull Long term anti-angiogenetic

sup1 Hallahan et al Oncology (Huntingt) 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 53

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Prostate cancer

bull Reduction of pain and bleeding in hormone refractory

prostate cancer (Kynaston Br J Urol 1990 Kawakami Nippon

Hinyokika Gakkai Zasshi 1993 Kalapurakal Int J Radiat Oncol Biol Phys

2003)

bull 100 improvement in patients with important hematuria (Carlton J Urol 1972)

Bladder cancer (Srinivasan et al Clin Oncol (R Coll Radiol) 1994)

bull 17 Gy in 2 fractions3 days 59 clearance of hematuria

bull 45 Gy in 12 fractions26 days 16 clearance of

hematuria

bull Selection by performance status Palliation (pain and

hematuria) better with hypofractionated RT worse

survival

bull No important side effects

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 54

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung cancer

bull Control of hemoptysis in up to 80 of patients (Brundage

Can J Oncol 1996 Medical Research Council Lung Cancer Working Party

Br J Cancer 1992 Hoskin in Doyle et al Second Edition New York

Oxford University Press 1998 Langendijk Int J Radiat Oncol Biol Phys

2000)

bull Optimal dosefractionation

ndash Hypofractionated RT seems to be equally effective to multiple

fractions (Rees Clin Oncol (R Coll Radiol) 1997 Sundstrom JCO

2004 Phase III Stevens Australas Radiol 1995 Phase III studies of

the MRC (s above)

ndash 10 Gy Single fraction equally effective to multiple fractions less

toxic (Hoskin in Doyle et al Second Edition New York Oxford

University Press 1998 Medical Research Council Lung Cancer

Working Party Br J Cancer 1992)

ndash Mostly total dose of around 20 Gy (multiple fractions) or 8 Gy

single fraction recommended

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 55

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Van Lonkhuijzen

Radiother Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 56

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gynaecologic tumours

bull Cf review van Lonkhuijzen Radiother Oncol 2011

bull Consider intracavitary HDR brachytherapy

Rectal cancer

bull Up to 85 control of rectal bleeding (Hoskin in Doyle et al Second Edition New York Oxford University Press 1998)

Kaposi sarcoma

bull Good palliation for pain bleeding or edema TD 15-40 Gy SD 2 Gy gt90 response 70 complete remission (Review Becker et al Onkologie 2006)

Skin tumours (Miller in Doyle Oxford Textbook of Palliative Medicine New York Oxford University Press 1993)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 57

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Duration of treatment effect

Lung cancer

bull Median duration of palliation 50 of remaining life span (30 Gy10d

27 Gy6d 17 Gy2 fract1w apart) (Medical Research Council Br J

Cancer 1991)

bull 1 fract 10 Gy vs 2 fract 85 Gy more patients need repeat RT (Medical Research Council Lung Cancer Working Party Br J Cancer 1992)

bull 417 pat need repeat RT within 3 m after 1x10 Gy (Scolaro Radiol

Med 1995)

Rec ovarian cancer

bull Median duration of palliation 4 m in 90 of patients until death (Corn Cancer 1994)

Cervical endometrial cancer

bull In 50 of patients pall Effect until death with 1-2x10 Gy

ndash Halle IJROBP 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 58

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull RT effective for improvement of

ndashThoracic symptoms (haemoptysis cough thoracic pain

dyspnoea airway obstruction) (Sirzeacuten Acta Oncol 2003 and others)

ndashQOL in about 13 of patients (Langendijk IJROBP 2000)

RT schedules

bull Systematic review (Fairchild JCO 264001-4011 2008)

ndash13 randomized trials 3473 patients

ndashdifferent RT schedules

ndashAim find optimal RT schedule for maximal palliation with

minimal toxicityneed for reirradiation

Thoracic symptoms

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz

Cancer

2007

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz Chow Hartsell Konski Cancer 2007

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Haemoptysis

bull Fig2 toux

733 689

812 802

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 62

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig3 doul thor 321 279

535 482

Cough

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 63

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 4 overall symptom burden

575 519

648 638

Thoracic pain

Fairchild JCO 2008

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 5 survie 1a

Cutoff (sensitivity analysis) BED[10] 35Gy vs LD

100 162

555 609

Overall symptom burden

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 65

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cutoff BED[10] 35Gy vs LD

265 217

Overall survival at 1y

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 66

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 7 Tox dysphagie

Cutoff BED[10] 30Gy vs LD

205 149

about x 2

Toxicity (dysphagia)

Fairchild JCO 2008

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomized trial 250 patients (Falk BMJ 2002)

bull Locally advanced non resectable NSCLC with minimal thoracic symptoms

bull Immediate vs delayed RT (at symptom onset)

bull In delayed arm 56 of patients died without RT

bull No difference in QOL odr OS

bull More acute toxicity in immediate RT arm

Randomized trial (Sundstrom Radiother Oncol 2005)

bull Advanced NSCLC

bull 2 RT schedules (5x4Gy vs 2x85 Gy) immediate RT

bull Stratification according to presenceabsence of thoracic symptoms

bull In asymptomatic patients no long term symptom control but important dysphagia

Timing

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull in 97 malignant

bull in 5-10 of lung cancer patients

bull Histology (exclude benign disease RT-chemosensible tumours

bull Generally spontanous improvement of symptoms by formation of collaterals

Superior vena cava syndrome

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Treatment

1 symptomatic

bull steroids

bull diuretics

bull Elevation of headthorax

2 causal bull chemotherapy (SCLC

lymphomas germinal tumours)

bull Endovascular stent placement

bull radiotherapy Palliative care in lung cancer ACCP

evidence- based clinical practice guidelines

(2nd edition)

Kvale Chest 2007

Superior vena cava syndrome

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

Radiotherapy

bull Mostly clinical response within 72 h

bull Complete clinical response at 2 w in 78 of patients with SCLC

and 63 of patients with NSCLC

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

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Duhamel Atlas clinique des maladies

des voies aeacuteriennes Elsevier

wwwupmccancercenterscom

Endobronchial brachytherapy

Cochrane analysis (Cardona The Cochrane

Library 2008)

bull No improved

symptom relief by

addition of

endobronchial

brachytherapy to

EBRT

bull Indicated in selected

patients pretreated

by EBRT with

central

endobronchial

obstruction

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Ozkok Lung Cancer 2008

Endobronchial brachytherapy

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Take home lung cancer

Dosefractionation

bull Minimum 10x3 Gy 5xw or equivalent

ndash better symptom control and better overall survival

ndash But more toxicity

bull Short schedule for symptom control and limited toxicity

ndashPoor performance status limited life expectancy

Timing

bull RT at the moment of symptom onset

bull No place for bdquoprophylactic palliative RTldquo according to evidence based guidelines

ndashExceptions

bull Young patient good PS aim of local control

bull Imminent symptoms (superior vena cava syndrome central airway obstruction

Rodrigues Pract Rad Oncol 2011

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

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Homs Eur J CancerLancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

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Randomisierte Studien

Homs Lancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

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Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

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Scoccianti Radiother Oncol 2012

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 100

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SRO Tutorial Palliative Care ndash Palliative Radiotherapy 101

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cancer 2010

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 13

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastases

bull What tumours

bull Does RT work

bull Causal and symptomatic effect (anti-tumour anti-

inflammatory)

bull How do you treat them Why Studies on fractionation

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 14

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

RT of bone metastases -

fractionation

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 15

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lievens RO 2000

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 16

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lievens RO 2000

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 17

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Konski Semin Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 18

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Konski Semin Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 19

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Overall

response

rate

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 20

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Complete

response

rate

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 21

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Retreat

ment

rate

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 22

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull EBRT significant palliation of painful bone metastasis in

50-80 of patients complete pain relief in up to 13 of

patients (Chow JCO 2007)

bull Optimal fractionation RT technique combination with other

treatment options

bull Systematic review combined with expert opinions

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 23

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Uncomplicated bone

metastasis

Single vs multiple

fractions

bull Pain relief

equivalent

bull Long term toxicity

equivalent

bull Single fraction

optimal patient and

caregiver

convenience

bull Retreatment rate

20 vs 8

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 24

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Repeat treatment of painful spinal metastasis

bull Pain relief in 46-80

bull Cave dose to spinal cord

bull Dosefractionation unclear

bull Recommendation prospective trial

Lutz IJROBP 2011

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Comparable fracture risk Chow Clin Oncol 2012

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 26

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Comparable risk of

spinal cord

compression

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 27

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SBRT of spinal metastasis

bull Mostly retrospective single-institution series

bull Recommendation prospective trial

bull Not primary treatment for spinal met causing spinal cord

compression

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 28

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Radionuclides

bull Important often underused option for multifocal bone

metastasis

bull For osteoblastic metastasis

bull Based on available data do not obviate need for EBRT

bull Recommendation prospective studies on prophylactic use

of radiopharmaceuticals in patients with limited bone

metastases combination with other systemic agents

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 29

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 30

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Biphosphonates

bull Several prospective studies on concurrent EBRT and

biphosphonates successful pain relief promotion of re-

ossification of damaged bone acceptable risk of toxicity

bull Not shown that combination better than EBRT alone for

pain relief

bull Recommendation prospective trial on optimum RT

fractionation EBRT versus radionuclides dose and

duration of biphosphonates and scheduling

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 31

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 32

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Denosumab

Lipton Curr Opp Supp Pall Care 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 33

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lipton Curr Opp Supp

Pall Care 2011

Denosumab versus

Zoledronate

Prevention of SREs (path fracture RT or OP to bone

spinal cord compression)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 34

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Breast

superior

Prostate

superior

Other solid

tumors or

multiple

myeloma

non inferior

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 35

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Vertebroplastykyphoplasty

bull No prospective data to suggest

that vertkyph obviates the

need for EBRT in painful bone

met

bull Small series of patients treated

by vertkyph plus EBRT

bull Recommendation prospective

trials on patient selection

efficacy toxicity and timing of

vertkyph and RT

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 36

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 37

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Non inferiority study

bull 272 patients randomized

Neuropathic pain

Roos Radiother Oncol 2005

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 39

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 40

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Spinal cord compression

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 41

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 42

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 43

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Patchell Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 44

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

RT short versus

long course

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 45

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 47

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 48

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 49

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 50

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull SRO tutorial CNS PD Dr A Pica

bull ScocciantiRicardi Radiother Oncol 2012 Review

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 51

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemorrhage

bull Bleeding in 6-10 of patients with advanced

cancer (Pereira et al Topics in Palliative Care Vol 4 New York

Oxford University Press 2000)

bull haemoptysis

bull haematemesis

bull haematocheziamelaena

bull vaginal bleeding

bull haematuria

bull bleeding in ulcerated skin lesions

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 52

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Mechanisms of haemostatic radiotherapy

bull Sparse literature

bull Coagulation activationsup1

ndash Oxydative endothelial damage

ndash Activation of thrombocytes

ndash Activation of inflammation

bull Long term anti-angiogenetic

sup1 Hallahan et al Oncology (Huntingt) 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 53

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Prostate cancer

bull Reduction of pain and bleeding in hormone refractory

prostate cancer (Kynaston Br J Urol 1990 Kawakami Nippon

Hinyokika Gakkai Zasshi 1993 Kalapurakal Int J Radiat Oncol Biol Phys

2003)

bull 100 improvement in patients with important hematuria (Carlton J Urol 1972)

Bladder cancer (Srinivasan et al Clin Oncol (R Coll Radiol) 1994)

bull 17 Gy in 2 fractions3 days 59 clearance of hematuria

bull 45 Gy in 12 fractions26 days 16 clearance of

hematuria

bull Selection by performance status Palliation (pain and

hematuria) better with hypofractionated RT worse

survival

bull No important side effects

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 54

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung cancer

bull Control of hemoptysis in up to 80 of patients (Brundage

Can J Oncol 1996 Medical Research Council Lung Cancer Working Party

Br J Cancer 1992 Hoskin in Doyle et al Second Edition New York

Oxford University Press 1998 Langendijk Int J Radiat Oncol Biol Phys

2000)

bull Optimal dosefractionation

ndash Hypofractionated RT seems to be equally effective to multiple

fractions (Rees Clin Oncol (R Coll Radiol) 1997 Sundstrom JCO

2004 Phase III Stevens Australas Radiol 1995 Phase III studies of

the MRC (s above)

ndash 10 Gy Single fraction equally effective to multiple fractions less

toxic (Hoskin in Doyle et al Second Edition New York Oxford

University Press 1998 Medical Research Council Lung Cancer

Working Party Br J Cancer 1992)

ndash Mostly total dose of around 20 Gy (multiple fractions) or 8 Gy

single fraction recommended

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 55

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Van Lonkhuijzen

Radiother Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 56

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gynaecologic tumours

bull Cf review van Lonkhuijzen Radiother Oncol 2011

bull Consider intracavitary HDR brachytherapy

Rectal cancer

bull Up to 85 control of rectal bleeding (Hoskin in Doyle et al Second Edition New York Oxford University Press 1998)

Kaposi sarcoma

bull Good palliation for pain bleeding or edema TD 15-40 Gy SD 2 Gy gt90 response 70 complete remission (Review Becker et al Onkologie 2006)

Skin tumours (Miller in Doyle Oxford Textbook of Palliative Medicine New York Oxford University Press 1993)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 57

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duration of treatment effect

Lung cancer

bull Median duration of palliation 50 of remaining life span (30 Gy10d

27 Gy6d 17 Gy2 fract1w apart) (Medical Research Council Br J

Cancer 1991)

bull 1 fract 10 Gy vs 2 fract 85 Gy more patients need repeat RT (Medical Research Council Lung Cancer Working Party Br J Cancer 1992)

bull 417 pat need repeat RT within 3 m after 1x10 Gy (Scolaro Radiol

Med 1995)

Rec ovarian cancer

bull Median duration of palliation 4 m in 90 of patients until death (Corn Cancer 1994)

Cervical endometrial cancer

bull In 50 of patients pall Effect until death with 1-2x10 Gy

ndash Halle IJROBP 1986

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull RT effective for improvement of

ndashThoracic symptoms (haemoptysis cough thoracic pain

dyspnoea airway obstruction) (Sirzeacuten Acta Oncol 2003 and others)

ndashQOL in about 13 of patients (Langendijk IJROBP 2000)

RT schedules

bull Systematic review (Fairchild JCO 264001-4011 2008)

ndash13 randomized trials 3473 patients

ndashdifferent RT schedules

ndashAim find optimal RT schedule for maximal palliation with

minimal toxicityneed for reirradiation

Thoracic symptoms

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz

Cancer

2007

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz Chow Hartsell Konski Cancer 2007

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Haemoptysis

bull Fig2 toux

733 689

812 802

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 62

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig3 doul thor 321 279

535 482

Cough

Fairchild JCO 2008

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 4 overall symptom burden

575 519

648 638

Thoracic pain

Fairchild JCO 2008

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 5 survie 1a

Cutoff (sensitivity analysis) BED[10] 35Gy vs LD

100 162

555 609

Overall symptom burden

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 65

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cutoff BED[10] 35Gy vs LD

265 217

Overall survival at 1y

Fairchild JCO 2008

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 7 Tox dysphagie

Cutoff BED[10] 30Gy vs LD

205 149

about x 2

Toxicity (dysphagia)

Fairchild JCO 2008

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomized trial 250 patients (Falk BMJ 2002)

bull Locally advanced non resectable NSCLC with minimal thoracic symptoms

bull Immediate vs delayed RT (at symptom onset)

bull In delayed arm 56 of patients died without RT

bull No difference in QOL odr OS

bull More acute toxicity in immediate RT arm

Randomized trial (Sundstrom Radiother Oncol 2005)

bull Advanced NSCLC

bull 2 RT schedules (5x4Gy vs 2x85 Gy) immediate RT

bull Stratification according to presenceabsence of thoracic symptoms

bull In asymptomatic patients no long term symptom control but important dysphagia

Timing

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull in 97 malignant

bull in 5-10 of lung cancer patients

bull Histology (exclude benign disease RT-chemosensible tumours

bull Generally spontanous improvement of symptoms by formation of collaterals

Superior vena cava syndrome

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Treatment

1 symptomatic

bull steroids

bull diuretics

bull Elevation of headthorax

2 causal bull chemotherapy (SCLC

lymphomas germinal tumours)

bull Endovascular stent placement

bull radiotherapy Palliative care in lung cancer ACCP

evidence- based clinical practice guidelines

(2nd edition)

Kvale Chest 2007

Superior vena cava syndrome

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

Radiotherapy

bull Mostly clinical response within 72 h

bull Complete clinical response at 2 w in 78 of patients with SCLC

and 63 of patients with NSCLC

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

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Duhamel Atlas clinique des maladies

des voies aeacuteriennes Elsevier

wwwupmccancercenterscom

Endobronchial brachytherapy

Cochrane analysis (Cardona The Cochrane

Library 2008)

bull No improved

symptom relief by

addition of

endobronchial

brachytherapy to

EBRT

bull Indicated in selected

patients pretreated

by EBRT with

central

endobronchial

obstruction

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 74

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Ozkok Lung Cancer 2008

Endobronchial brachytherapy

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Take home lung cancer

Dosefractionation

bull Minimum 10x3 Gy 5xw or equivalent

ndash better symptom control and better overall survival

ndash But more toxicity

bull Short schedule for symptom control and limited toxicity

ndashPoor performance status limited life expectancy

Timing

bull RT at the moment of symptom onset

bull No place for bdquoprophylactic palliative RTldquo according to evidence based guidelines

ndashExceptions

bull Young patient good PS aim of local control

bull Imminent symptoms (superior vena cava syndrome central airway obstruction

Rodrigues Pract Rad Oncol 2011

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 80

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

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Homs Eur J CancerLancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

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Scoccianti Radiother Oncol 2012

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SRO Tutorial Palliative Care ndash Palliative Radiotherapy 13

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastases

bull What tumours

bull Does RT work

bull Causal and symptomatic effect (anti-tumour anti-

inflammatory)

bull How do you treat them Why Studies on fractionation

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 14

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

RT of bone metastases -

fractionation

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 15

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lievens RO 2000

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 16

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lievens RO 2000

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 17

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Konski Semin Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 18

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Konski Semin Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 19

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Overall

response

rate

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 20

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Complete

response

rate

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 21

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Retreat

ment

rate

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 22

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull EBRT significant palliation of painful bone metastasis in

50-80 of patients complete pain relief in up to 13 of

patients (Chow JCO 2007)

bull Optimal fractionation RT technique combination with other

treatment options

bull Systematic review combined with expert opinions

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 23

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Uncomplicated bone

metastasis

Single vs multiple

fractions

bull Pain relief

equivalent

bull Long term toxicity

equivalent

bull Single fraction

optimal patient and

caregiver

convenience

bull Retreatment rate

20 vs 8

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 24

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Repeat treatment of painful spinal metastasis

bull Pain relief in 46-80

bull Cave dose to spinal cord

bull Dosefractionation unclear

bull Recommendation prospective trial

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 25

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Comparable fracture risk Chow Clin Oncol 2012

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 26

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Comparable risk of

spinal cord

compression

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 27

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SBRT of spinal metastasis

bull Mostly retrospective single-institution series

bull Recommendation prospective trial

bull Not primary treatment for spinal met causing spinal cord

compression

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 28

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Radionuclides

bull Important often underused option for multifocal bone

metastasis

bull For osteoblastic metastasis

bull Based on available data do not obviate need for EBRT

bull Recommendation prospective studies on prophylactic use

of radiopharmaceuticals in patients with limited bone

metastases combination with other systemic agents

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 29

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 30

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Biphosphonates

bull Several prospective studies on concurrent EBRT and

biphosphonates successful pain relief promotion of re-

ossification of damaged bone acceptable risk of toxicity

bull Not shown that combination better than EBRT alone for

pain relief

bull Recommendation prospective trial on optimum RT

fractionation EBRT versus radionuclides dose and

duration of biphosphonates and scheduling

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 31

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 32

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Denosumab

Lipton Curr Opp Supp Pall Care 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 33

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lipton Curr Opp Supp

Pall Care 2011

Denosumab versus

Zoledronate

Prevention of SREs (path fracture RT or OP to bone

spinal cord compression)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 34

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Breast

superior

Prostate

superior

Other solid

tumors or

multiple

myeloma

non inferior

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 35

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Vertebroplastykyphoplasty

bull No prospective data to suggest

that vertkyph obviates the

need for EBRT in painful bone

met

bull Small series of patients treated

by vertkyph plus EBRT

bull Recommendation prospective

trials on patient selection

efficacy toxicity and timing of

vertkyph and RT

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 36

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 37

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Non inferiority study

bull 272 patients randomized

Neuropathic pain

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 38

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 39

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 40

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Spinal cord compression

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 41

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 42

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 43

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Patchell Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 44

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

RT short versus

long course

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 45

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 46

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 47

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 48

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 49

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 50

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull SRO tutorial CNS PD Dr A Pica

bull ScocciantiRicardi Radiother Oncol 2012 Review

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 51

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemorrhage

bull Bleeding in 6-10 of patients with advanced

cancer (Pereira et al Topics in Palliative Care Vol 4 New York

Oxford University Press 2000)

bull haemoptysis

bull haematemesis

bull haematocheziamelaena

bull vaginal bleeding

bull haematuria

bull bleeding in ulcerated skin lesions

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 52

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Mechanisms of haemostatic radiotherapy

bull Sparse literature

bull Coagulation activationsup1

ndash Oxydative endothelial damage

ndash Activation of thrombocytes

ndash Activation of inflammation

bull Long term anti-angiogenetic

sup1 Hallahan et al Oncology (Huntingt) 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 53

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Prostate cancer

bull Reduction of pain and bleeding in hormone refractory

prostate cancer (Kynaston Br J Urol 1990 Kawakami Nippon

Hinyokika Gakkai Zasshi 1993 Kalapurakal Int J Radiat Oncol Biol Phys

2003)

bull 100 improvement in patients with important hematuria (Carlton J Urol 1972)

Bladder cancer (Srinivasan et al Clin Oncol (R Coll Radiol) 1994)

bull 17 Gy in 2 fractions3 days 59 clearance of hematuria

bull 45 Gy in 12 fractions26 days 16 clearance of

hematuria

bull Selection by performance status Palliation (pain and

hematuria) better with hypofractionated RT worse

survival

bull No important side effects

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 54

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung cancer

bull Control of hemoptysis in up to 80 of patients (Brundage

Can J Oncol 1996 Medical Research Council Lung Cancer Working Party

Br J Cancer 1992 Hoskin in Doyle et al Second Edition New York

Oxford University Press 1998 Langendijk Int J Radiat Oncol Biol Phys

2000)

bull Optimal dosefractionation

ndash Hypofractionated RT seems to be equally effective to multiple

fractions (Rees Clin Oncol (R Coll Radiol) 1997 Sundstrom JCO

2004 Phase III Stevens Australas Radiol 1995 Phase III studies of

the MRC (s above)

ndash 10 Gy Single fraction equally effective to multiple fractions less

toxic (Hoskin in Doyle et al Second Edition New York Oxford

University Press 1998 Medical Research Council Lung Cancer

Working Party Br J Cancer 1992)

ndash Mostly total dose of around 20 Gy (multiple fractions) or 8 Gy

single fraction recommended

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 55

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Van Lonkhuijzen

Radiother Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 56

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gynaecologic tumours

bull Cf review van Lonkhuijzen Radiother Oncol 2011

bull Consider intracavitary HDR brachytherapy

Rectal cancer

bull Up to 85 control of rectal bleeding (Hoskin in Doyle et al Second Edition New York Oxford University Press 1998)

Kaposi sarcoma

bull Good palliation for pain bleeding or edema TD 15-40 Gy SD 2 Gy gt90 response 70 complete remission (Review Becker et al Onkologie 2006)

Skin tumours (Miller in Doyle Oxford Textbook of Palliative Medicine New York Oxford University Press 1993)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 57

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duration of treatment effect

Lung cancer

bull Median duration of palliation 50 of remaining life span (30 Gy10d

27 Gy6d 17 Gy2 fract1w apart) (Medical Research Council Br J

Cancer 1991)

bull 1 fract 10 Gy vs 2 fract 85 Gy more patients need repeat RT (Medical Research Council Lung Cancer Working Party Br J Cancer 1992)

bull 417 pat need repeat RT within 3 m after 1x10 Gy (Scolaro Radiol

Med 1995)

Rec ovarian cancer

bull Median duration of palliation 4 m in 90 of patients until death (Corn Cancer 1994)

Cervical endometrial cancer

bull In 50 of patients pall Effect until death with 1-2x10 Gy

ndash Halle IJROBP 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 58

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull RT effective for improvement of

ndashThoracic symptoms (haemoptysis cough thoracic pain

dyspnoea airway obstruction) (Sirzeacuten Acta Oncol 2003 and others)

ndashQOL in about 13 of patients (Langendijk IJROBP 2000)

RT schedules

bull Systematic review (Fairchild JCO 264001-4011 2008)

ndash13 randomized trials 3473 patients

ndashdifferent RT schedules

ndashAim find optimal RT schedule for maximal palliation with

minimal toxicityneed for reirradiation

Thoracic symptoms

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 59

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz

Cancer

2007

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz Chow Hartsell Konski Cancer 2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 61

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemoptysis

bull Fig2 toux

733 689

812 802

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 62

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig3 doul thor 321 279

535 482

Cough

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 63

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 4 overall symptom burden

575 519

648 638

Thoracic pain

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 64

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 5 survie 1a

Cutoff (sensitivity analysis) BED[10] 35Gy vs LD

100 162

555 609

Overall symptom burden

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 65

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cutoff BED[10] 35Gy vs LD

265 217

Overall survival at 1y

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 66

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 7 Tox dysphagie

Cutoff BED[10] 30Gy vs LD

205 149

about x 2

Toxicity (dysphagia)

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 67

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomized trial 250 patients (Falk BMJ 2002)

bull Locally advanced non resectable NSCLC with minimal thoracic symptoms

bull Immediate vs delayed RT (at symptom onset)

bull In delayed arm 56 of patients died without RT

bull No difference in QOL odr OS

bull More acute toxicity in immediate RT arm

Randomized trial (Sundstrom Radiother Oncol 2005)

bull Advanced NSCLC

bull 2 RT schedules (5x4Gy vs 2x85 Gy) immediate RT

bull Stratification according to presenceabsence of thoracic symptoms

bull In asymptomatic patients no long term symptom control but important dysphagia

Timing

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 68

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull in 97 malignant

bull in 5-10 of lung cancer patients

bull Histology (exclude benign disease RT-chemosensible tumours

bull Generally spontanous improvement of symptoms by formation of collaterals

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 69

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Treatment

1 symptomatic

bull steroids

bull diuretics

bull Elevation of headthorax

2 causal bull chemotherapy (SCLC

lymphomas germinal tumours)

bull Endovascular stent placement

bull radiotherapy Palliative care in lung cancer ACCP

evidence- based clinical practice guidelines

(2nd edition)

Kvale Chest 2007

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 70

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

Radiotherapy

bull Mostly clinical response within 72 h

bull Complete clinical response at 2 w in 78 of patients with SCLC

and 63 of patients with NSCLC

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 73

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duhamel Atlas clinique des maladies

des voies aeacuteriennes Elsevier

wwwupmccancercenterscom

Endobronchial brachytherapy

Cochrane analysis (Cardona The Cochrane

Library 2008)

bull No improved

symptom relief by

addition of

endobronchial

brachytherapy to

EBRT

bull Indicated in selected

patients pretreated

by EBRT with

central

endobronchial

obstruction

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 74

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Ozkok Lung Cancer 2008

Endobronchial brachytherapy

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Take home lung cancer

Dosefractionation

bull Minimum 10x3 Gy 5xw or equivalent

ndash better symptom control and better overall survival

ndash But more toxicity

bull Short schedule for symptom control and limited toxicity

ndashPoor performance status limited life expectancy

Timing

bull RT at the moment of symptom onset

bull No place for bdquoprophylactic palliative RTldquo according to evidence based guidelines

ndashExceptions

bull Young patient good PS aim of local control

bull Imminent symptoms (superior vena cava syndrome central airway obstruction

Rodrigues Pract Rad Oncol 2011

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 80

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 82

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 83

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 84

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 85

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 90

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References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

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Scoccianti Radiother Oncol 2012

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

RT of bone metastases -

fractionation

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 15

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lievens RO 2000

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Lievens RO 2000

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Konski Semin Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 18

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Konski Semin Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 19

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Overall

response

rate

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 20

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Complete

response

rate

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Retreat

ment

rate

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 22

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull EBRT significant palliation of painful bone metastasis in

50-80 of patients complete pain relief in up to 13 of

patients (Chow JCO 2007)

bull Optimal fractionation RT technique combination with other

treatment options

bull Systematic review combined with expert opinions

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 23

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Uncomplicated bone

metastasis

Single vs multiple

fractions

bull Pain relief

equivalent

bull Long term toxicity

equivalent

bull Single fraction

optimal patient and

caregiver

convenience

bull Retreatment rate

20 vs 8

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 24

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Repeat treatment of painful spinal metastasis

bull Pain relief in 46-80

bull Cave dose to spinal cord

bull Dosefractionation unclear

bull Recommendation prospective trial

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 25

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Comparable fracture risk Chow Clin Oncol 2012

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 26

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Comparable risk of

spinal cord

compression

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 27

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SBRT of spinal metastasis

bull Mostly retrospective single-institution series

bull Recommendation prospective trial

bull Not primary treatment for spinal met causing spinal cord

compression

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 28

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Radionuclides

bull Important often underused option for multifocal bone

metastasis

bull For osteoblastic metastasis

bull Based on available data do not obviate need for EBRT

bull Recommendation prospective studies on prophylactic use

of radiopharmaceuticals in patients with limited bone

metastases combination with other systemic agents

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 29

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 30

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Biphosphonates

bull Several prospective studies on concurrent EBRT and

biphosphonates successful pain relief promotion of re-

ossification of damaged bone acceptable risk of toxicity

bull Not shown that combination better than EBRT alone for

pain relief

bull Recommendation prospective trial on optimum RT

fractionation EBRT versus radionuclides dose and

duration of biphosphonates and scheduling

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 31

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 32

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Denosumab

Lipton Curr Opp Supp Pall Care 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 33

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lipton Curr Opp Supp

Pall Care 2011

Denosumab versus

Zoledronate

Prevention of SREs (path fracture RT or OP to bone

spinal cord compression)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 34

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Breast

superior

Prostate

superior

Other solid

tumors or

multiple

myeloma

non inferior

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 35

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Vertebroplastykyphoplasty

bull No prospective data to suggest

that vertkyph obviates the

need for EBRT in painful bone

met

bull Small series of patients treated

by vertkyph plus EBRT

bull Recommendation prospective

trials on patient selection

efficacy toxicity and timing of

vertkyph and RT

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 36

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 37

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Non inferiority study

bull 272 patients randomized

Neuropathic pain

Roos Radiother Oncol 2005

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 39

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 40

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Spinal cord compression

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lancet 2005

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Patchell Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 44

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

RT short versus

long course

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 45

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 47

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 48

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 50

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull SRO tutorial CNS PD Dr A Pica

bull ScocciantiRicardi Radiother Oncol 2012 Review

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 51

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemorrhage

bull Bleeding in 6-10 of patients with advanced

cancer (Pereira et al Topics in Palliative Care Vol 4 New York

Oxford University Press 2000)

bull haemoptysis

bull haematemesis

bull haematocheziamelaena

bull vaginal bleeding

bull haematuria

bull bleeding in ulcerated skin lesions

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 52

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Mechanisms of haemostatic radiotherapy

bull Sparse literature

bull Coagulation activationsup1

ndash Oxydative endothelial damage

ndash Activation of thrombocytes

ndash Activation of inflammation

bull Long term anti-angiogenetic

sup1 Hallahan et al Oncology (Huntingt) 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 53

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Prostate cancer

bull Reduction of pain and bleeding in hormone refractory

prostate cancer (Kynaston Br J Urol 1990 Kawakami Nippon

Hinyokika Gakkai Zasshi 1993 Kalapurakal Int J Radiat Oncol Biol Phys

2003)

bull 100 improvement in patients with important hematuria (Carlton J Urol 1972)

Bladder cancer (Srinivasan et al Clin Oncol (R Coll Radiol) 1994)

bull 17 Gy in 2 fractions3 days 59 clearance of hematuria

bull 45 Gy in 12 fractions26 days 16 clearance of

hematuria

bull Selection by performance status Palliation (pain and

hematuria) better with hypofractionated RT worse

survival

bull No important side effects

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 54

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung cancer

bull Control of hemoptysis in up to 80 of patients (Brundage

Can J Oncol 1996 Medical Research Council Lung Cancer Working Party

Br J Cancer 1992 Hoskin in Doyle et al Second Edition New York

Oxford University Press 1998 Langendijk Int J Radiat Oncol Biol Phys

2000)

bull Optimal dosefractionation

ndash Hypofractionated RT seems to be equally effective to multiple

fractions (Rees Clin Oncol (R Coll Radiol) 1997 Sundstrom JCO

2004 Phase III Stevens Australas Radiol 1995 Phase III studies of

the MRC (s above)

ndash 10 Gy Single fraction equally effective to multiple fractions less

toxic (Hoskin in Doyle et al Second Edition New York Oxford

University Press 1998 Medical Research Council Lung Cancer

Working Party Br J Cancer 1992)

ndash Mostly total dose of around 20 Gy (multiple fractions) or 8 Gy

single fraction recommended

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 55

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Van Lonkhuijzen

Radiother Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 56

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Gynaecologic tumours

bull Cf review van Lonkhuijzen Radiother Oncol 2011

bull Consider intracavitary HDR brachytherapy

Rectal cancer

bull Up to 85 control of rectal bleeding (Hoskin in Doyle et al Second Edition New York Oxford University Press 1998)

Kaposi sarcoma

bull Good palliation for pain bleeding or edema TD 15-40 Gy SD 2 Gy gt90 response 70 complete remission (Review Becker et al Onkologie 2006)

Skin tumours (Miller in Doyle Oxford Textbook of Palliative Medicine New York Oxford University Press 1993)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 57

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duration of treatment effect

Lung cancer

bull Median duration of palliation 50 of remaining life span (30 Gy10d

27 Gy6d 17 Gy2 fract1w apart) (Medical Research Council Br J

Cancer 1991)

bull 1 fract 10 Gy vs 2 fract 85 Gy more patients need repeat RT (Medical Research Council Lung Cancer Working Party Br J Cancer 1992)

bull 417 pat need repeat RT within 3 m after 1x10 Gy (Scolaro Radiol

Med 1995)

Rec ovarian cancer

bull Median duration of palliation 4 m in 90 of patients until death (Corn Cancer 1994)

Cervical endometrial cancer

bull In 50 of patients pall Effect until death with 1-2x10 Gy

ndash Halle IJROBP 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 58

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull RT effective for improvement of

ndashThoracic symptoms (haemoptysis cough thoracic pain

dyspnoea airway obstruction) (Sirzeacuten Acta Oncol 2003 and others)

ndashQOL in about 13 of patients (Langendijk IJROBP 2000)

RT schedules

bull Systematic review (Fairchild JCO 264001-4011 2008)

ndash13 randomized trials 3473 patients

ndashdifferent RT schedules

ndashAim find optimal RT schedule for maximal palliation with

minimal toxicityneed for reirradiation

Thoracic symptoms

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz

Cancer

2007

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Lutz Chow Hartsell Konski Cancer 2007

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Haemoptysis

bull Fig2 toux

733 689

812 802

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 62

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig3 doul thor 321 279

535 482

Cough

Fairchild JCO 2008

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 4 overall symptom burden

575 519

648 638

Thoracic pain

Fairchild JCO 2008

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 5 survie 1a

Cutoff (sensitivity analysis) BED[10] 35Gy vs LD

100 162

555 609

Overall symptom burden

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 65

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cutoff BED[10] 35Gy vs LD

265 217

Overall survival at 1y

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 66

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 7 Tox dysphagie

Cutoff BED[10] 30Gy vs LD

205 149

about x 2

Toxicity (dysphagia)

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 67

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomized trial 250 patients (Falk BMJ 2002)

bull Locally advanced non resectable NSCLC with minimal thoracic symptoms

bull Immediate vs delayed RT (at symptom onset)

bull In delayed arm 56 of patients died without RT

bull No difference in QOL odr OS

bull More acute toxicity in immediate RT arm

Randomized trial (Sundstrom Radiother Oncol 2005)

bull Advanced NSCLC

bull 2 RT schedules (5x4Gy vs 2x85 Gy) immediate RT

bull Stratification according to presenceabsence of thoracic symptoms

bull In asymptomatic patients no long term symptom control but important dysphagia

Timing

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull in 97 malignant

bull in 5-10 of lung cancer patients

bull Histology (exclude benign disease RT-chemosensible tumours

bull Generally spontanous improvement of symptoms by formation of collaterals

Superior vena cava syndrome

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Treatment

1 symptomatic

bull steroids

bull diuretics

bull Elevation of headthorax

2 causal bull chemotherapy (SCLC

lymphomas germinal tumours)

bull Endovascular stent placement

bull radiotherapy Palliative care in lung cancer ACCP

evidence- based clinical practice guidelines

(2nd edition)

Kvale Chest 2007

Superior vena cava syndrome

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

Radiotherapy

bull Mostly clinical response within 72 h

bull Complete clinical response at 2 w in 78 of patients with SCLC

and 63 of patients with NSCLC

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

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Duhamel Atlas clinique des maladies

des voies aeacuteriennes Elsevier

wwwupmccancercenterscom

Endobronchial brachytherapy

Cochrane analysis (Cardona The Cochrane

Library 2008)

bull No improved

symptom relief by

addition of

endobronchial

brachytherapy to

EBRT

bull Indicated in selected

patients pretreated

by EBRT with

central

endobronchial

obstruction

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 74

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Ozkok Lung Cancer 2008

Endobronchial brachytherapy

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Take home lung cancer

Dosefractionation

bull Minimum 10x3 Gy 5xw or equivalent

ndash better symptom control and better overall survival

ndash But more toxicity

bull Short schedule for symptom control and limited toxicity

ndashPoor performance status limited life expectancy

Timing

bull RT at the moment of symptom onset

bull No place for bdquoprophylactic palliative RTldquo according to evidence based guidelines

ndashExceptions

bull Young patient good PS aim of local control

bull Imminent symptoms (superior vena cava syndrome central airway obstruction

Rodrigues Pract Rad Oncol 2011

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 80

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

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Homs Eur J CancerLancet 2004

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ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

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Randomisierte Studien

Homs Lancet 2004

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Randomisierte Studien

Homs Lancet 2004

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bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

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Thanks

Questions

Discussion

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

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bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

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Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

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Scoccianti Radiother Oncol 2012

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lievens RO 2000

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Lievens RO 2000

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Konski Semin Oncol 2005

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Konski Semin Oncol 2005

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Overall

response

rate

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Chow Clin Oncol 2012

Complete

response

rate

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Chow Clin Oncol 2012

Retreat

ment

rate

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull EBRT significant palliation of painful bone metastasis in

50-80 of patients complete pain relief in up to 13 of

patients (Chow JCO 2007)

bull Optimal fractionation RT technique combination with other

treatment options

bull Systematic review combined with expert opinions

Lutz IJROBP 2011

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Uncomplicated bone

metastasis

Single vs multiple

fractions

bull Pain relief

equivalent

bull Long term toxicity

equivalent

bull Single fraction

optimal patient and

caregiver

convenience

bull Retreatment rate

20 vs 8

Lutz IJROBP 2011

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Repeat treatment of painful spinal metastasis

bull Pain relief in 46-80

bull Cave dose to spinal cord

bull Dosefractionation unclear

bull Recommendation prospective trial

Lutz IJROBP 2011

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Comparable fracture risk Chow Clin Oncol 2012

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Chow Clin Oncol 2012

Comparable risk of

spinal cord

compression

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SBRT of spinal metastasis

bull Mostly retrospective single-institution series

bull Recommendation prospective trial

bull Not primary treatment for spinal met causing spinal cord

compression

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 28

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Radionuclides

bull Important often underused option for multifocal bone

metastasis

bull For osteoblastic metastasis

bull Based on available data do not obviate need for EBRT

bull Recommendation prospective studies on prophylactic use

of radiopharmaceuticals in patients with limited bone

metastases combination with other systemic agents

Lutz IJROBP 2011

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

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Biphosphonates

bull Several prospective studies on concurrent EBRT and

biphosphonates successful pain relief promotion of re-

ossification of damaged bone acceptable risk of toxicity

bull Not shown that combination better than EBRT alone for

pain relief

bull Recommendation prospective trial on optimum RT

fractionation EBRT versus radionuclides dose and

duration of biphosphonates and scheduling

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Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 32

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Denosumab

Lipton Curr Opp Supp Pall Care 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 33

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lipton Curr Opp Supp

Pall Care 2011

Denosumab versus

Zoledronate

Prevention of SREs (path fracture RT or OP to bone

spinal cord compression)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 34

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Breast

superior

Prostate

superior

Other solid

tumors or

multiple

myeloma

non inferior

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 35

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Vertebroplastykyphoplasty

bull No prospective data to suggest

that vertkyph obviates the

need for EBRT in painful bone

met

bull Small series of patients treated

by vertkyph plus EBRT

bull Recommendation prospective

trials on patient selection

efficacy toxicity and timing of

vertkyph and RT

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 36

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 37

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Non inferiority study

bull 272 patients randomized

Neuropathic pain

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 38

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 39

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 40

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Spinal cord compression

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 41

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 42

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 43

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Patchell Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 44

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

RT short versus

long course

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 45

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 46

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 47

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 48

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 49

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 50

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull SRO tutorial CNS PD Dr A Pica

bull ScocciantiRicardi Radiother Oncol 2012 Review

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 51

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemorrhage

bull Bleeding in 6-10 of patients with advanced

cancer (Pereira et al Topics in Palliative Care Vol 4 New York

Oxford University Press 2000)

bull haemoptysis

bull haematemesis

bull haematocheziamelaena

bull vaginal bleeding

bull haematuria

bull bleeding in ulcerated skin lesions

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 52

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Mechanisms of haemostatic radiotherapy

bull Sparse literature

bull Coagulation activationsup1

ndash Oxydative endothelial damage

ndash Activation of thrombocytes

ndash Activation of inflammation

bull Long term anti-angiogenetic

sup1 Hallahan et al Oncology (Huntingt) 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 53

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Prostate cancer

bull Reduction of pain and bleeding in hormone refractory

prostate cancer (Kynaston Br J Urol 1990 Kawakami Nippon

Hinyokika Gakkai Zasshi 1993 Kalapurakal Int J Radiat Oncol Biol Phys

2003)

bull 100 improvement in patients with important hematuria (Carlton J Urol 1972)

Bladder cancer (Srinivasan et al Clin Oncol (R Coll Radiol) 1994)

bull 17 Gy in 2 fractions3 days 59 clearance of hematuria

bull 45 Gy in 12 fractions26 days 16 clearance of

hematuria

bull Selection by performance status Palliation (pain and

hematuria) better with hypofractionated RT worse

survival

bull No important side effects

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 54

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung cancer

bull Control of hemoptysis in up to 80 of patients (Brundage

Can J Oncol 1996 Medical Research Council Lung Cancer Working Party

Br J Cancer 1992 Hoskin in Doyle et al Second Edition New York

Oxford University Press 1998 Langendijk Int J Radiat Oncol Biol Phys

2000)

bull Optimal dosefractionation

ndash Hypofractionated RT seems to be equally effective to multiple

fractions (Rees Clin Oncol (R Coll Radiol) 1997 Sundstrom JCO

2004 Phase III Stevens Australas Radiol 1995 Phase III studies of

the MRC (s above)

ndash 10 Gy Single fraction equally effective to multiple fractions less

toxic (Hoskin in Doyle et al Second Edition New York Oxford

University Press 1998 Medical Research Council Lung Cancer

Working Party Br J Cancer 1992)

ndash Mostly total dose of around 20 Gy (multiple fractions) or 8 Gy

single fraction recommended

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 55

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Van Lonkhuijzen

Radiother Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 56

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gynaecologic tumours

bull Cf review van Lonkhuijzen Radiother Oncol 2011

bull Consider intracavitary HDR brachytherapy

Rectal cancer

bull Up to 85 control of rectal bleeding (Hoskin in Doyle et al Second Edition New York Oxford University Press 1998)

Kaposi sarcoma

bull Good palliation for pain bleeding or edema TD 15-40 Gy SD 2 Gy gt90 response 70 complete remission (Review Becker et al Onkologie 2006)

Skin tumours (Miller in Doyle Oxford Textbook of Palliative Medicine New York Oxford University Press 1993)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 57

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duration of treatment effect

Lung cancer

bull Median duration of palliation 50 of remaining life span (30 Gy10d

27 Gy6d 17 Gy2 fract1w apart) (Medical Research Council Br J

Cancer 1991)

bull 1 fract 10 Gy vs 2 fract 85 Gy more patients need repeat RT (Medical Research Council Lung Cancer Working Party Br J Cancer 1992)

bull 417 pat need repeat RT within 3 m after 1x10 Gy (Scolaro Radiol

Med 1995)

Rec ovarian cancer

bull Median duration of palliation 4 m in 90 of patients until death (Corn Cancer 1994)

Cervical endometrial cancer

bull In 50 of patients pall Effect until death with 1-2x10 Gy

ndash Halle IJROBP 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 58

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull RT effective for improvement of

ndashThoracic symptoms (haemoptysis cough thoracic pain

dyspnoea airway obstruction) (Sirzeacuten Acta Oncol 2003 and others)

ndashQOL in about 13 of patients (Langendijk IJROBP 2000)

RT schedules

bull Systematic review (Fairchild JCO 264001-4011 2008)

ndash13 randomized trials 3473 patients

ndashdifferent RT schedules

ndashAim find optimal RT schedule for maximal palliation with

minimal toxicityneed for reirradiation

Thoracic symptoms

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 59

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz

Cancer

2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 60

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz Chow Hartsell Konski Cancer 2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 61

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemoptysis

bull Fig2 toux

733 689

812 802

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 62

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig3 doul thor 321 279

535 482

Cough

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 63

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 4 overall symptom burden

575 519

648 638

Thoracic pain

Fairchild JCO 2008

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 5 survie 1a

Cutoff (sensitivity analysis) BED[10] 35Gy vs LD

100 162

555 609

Overall symptom burden

Fairchild JCO 2008

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cutoff BED[10] 35Gy vs LD

265 217

Overall survival at 1y

Fairchild JCO 2008

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 7 Tox dysphagie

Cutoff BED[10] 30Gy vs LD

205 149

about x 2

Toxicity (dysphagia)

Fairchild JCO 2008

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomized trial 250 patients (Falk BMJ 2002)

bull Locally advanced non resectable NSCLC with minimal thoracic symptoms

bull Immediate vs delayed RT (at symptom onset)

bull In delayed arm 56 of patients died without RT

bull No difference in QOL odr OS

bull More acute toxicity in immediate RT arm

Randomized trial (Sundstrom Radiother Oncol 2005)

bull Advanced NSCLC

bull 2 RT schedules (5x4Gy vs 2x85 Gy) immediate RT

bull Stratification according to presenceabsence of thoracic symptoms

bull In asymptomatic patients no long term symptom control but important dysphagia

Timing

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 68

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull in 97 malignant

bull in 5-10 of lung cancer patients

bull Histology (exclude benign disease RT-chemosensible tumours

bull Generally spontanous improvement of symptoms by formation of collaterals

Superior vena cava syndrome

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Treatment

1 symptomatic

bull steroids

bull diuretics

bull Elevation of headthorax

2 causal bull chemotherapy (SCLC

lymphomas germinal tumours)

bull Endovascular stent placement

bull radiotherapy Palliative care in lung cancer ACCP

evidence- based clinical practice guidelines

(2nd edition)

Kvale Chest 2007

Superior vena cava syndrome

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

Radiotherapy

bull Mostly clinical response within 72 h

bull Complete clinical response at 2 w in 78 of patients with SCLC

and 63 of patients with NSCLC

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duhamel Atlas clinique des maladies

des voies aeacuteriennes Elsevier

wwwupmccancercenterscom

Endobronchial brachytherapy

Cochrane analysis (Cardona The Cochrane

Library 2008)

bull No improved

symptom relief by

addition of

endobronchial

brachytherapy to

EBRT

bull Indicated in selected

patients pretreated

by EBRT with

central

endobronchial

obstruction

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Ozkok Lung Cancer 2008

Endobronchial brachytherapy

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Take home lung cancer

Dosefractionation

bull Minimum 10x3 Gy 5xw or equivalent

ndash better symptom control and better overall survival

ndash But more toxicity

bull Short schedule for symptom control and limited toxicity

ndashPoor performance status limited life expectancy

Timing

bull RT at the moment of symptom onset

bull No place for bdquoprophylactic palliative RTldquo according to evidence based guidelines

ndashExceptions

bull Young patient good PS aim of local control

bull Imminent symptoms (superior vena cava syndrome central airway obstruction

Rodrigues Pract Rad Oncol 2011

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

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Homs Eur J CancerLancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

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Randomisierte Studien

Homs Lancet 2004

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Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

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Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

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Scoccianti Radiother Oncol 2012

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Page 16: SRO Tutorial Palliative Care 04.05.2012 Palliative Radiotherapy · 2018-02-22 · SRO Tutorial Palliative Care – Palliative Radiotherapy 30 Jacqueline Vock, Universitätsklinik

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lievens RO 2000

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Konski Semin Oncol 2005

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Konski Semin Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 19

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Overall

response

rate

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Complete

response

rate

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Retreat

ment

rate

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull EBRT significant palliation of painful bone metastasis in

50-80 of patients complete pain relief in up to 13 of

patients (Chow JCO 2007)

bull Optimal fractionation RT technique combination with other

treatment options

bull Systematic review combined with expert opinions

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 23

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Uncomplicated bone

metastasis

Single vs multiple

fractions

bull Pain relief

equivalent

bull Long term toxicity

equivalent

bull Single fraction

optimal patient and

caregiver

convenience

bull Retreatment rate

20 vs 8

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 24

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Repeat treatment of painful spinal metastasis

bull Pain relief in 46-80

bull Cave dose to spinal cord

bull Dosefractionation unclear

bull Recommendation prospective trial

Lutz IJROBP 2011

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Comparable fracture risk Chow Clin Oncol 2012

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 26

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Comparable risk of

spinal cord

compression

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 27

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SBRT of spinal metastasis

bull Mostly retrospective single-institution series

bull Recommendation prospective trial

bull Not primary treatment for spinal met causing spinal cord

compression

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 28

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Radionuclides

bull Important often underused option for multifocal bone

metastasis

bull For osteoblastic metastasis

bull Based on available data do not obviate need for EBRT

bull Recommendation prospective studies on prophylactic use

of radiopharmaceuticals in patients with limited bone

metastases combination with other systemic agents

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 29

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 30

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Biphosphonates

bull Several prospective studies on concurrent EBRT and

biphosphonates successful pain relief promotion of re-

ossification of damaged bone acceptable risk of toxicity

bull Not shown that combination better than EBRT alone for

pain relief

bull Recommendation prospective trial on optimum RT

fractionation EBRT versus radionuclides dose and

duration of biphosphonates and scheduling

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 31

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 32

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Denosumab

Lipton Curr Opp Supp Pall Care 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 33

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lipton Curr Opp Supp

Pall Care 2011

Denosumab versus

Zoledronate

Prevention of SREs (path fracture RT or OP to bone

spinal cord compression)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 34

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Breast

superior

Prostate

superior

Other solid

tumors or

multiple

myeloma

non inferior

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 35

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Vertebroplastykyphoplasty

bull No prospective data to suggest

that vertkyph obviates the

need for EBRT in painful bone

met

bull Small series of patients treated

by vertkyph plus EBRT

bull Recommendation prospective

trials on patient selection

efficacy toxicity and timing of

vertkyph and RT

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 36

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 37

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Non inferiority study

bull 272 patients randomized

Neuropathic pain

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 38

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 39

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 40

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Spinal cord compression

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 41

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 42

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 43

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Patchell Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 44

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

RT short versus

long course

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 45

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 46

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 47

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 48

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 49

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 50

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull SRO tutorial CNS PD Dr A Pica

bull ScocciantiRicardi Radiother Oncol 2012 Review

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 51

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemorrhage

bull Bleeding in 6-10 of patients with advanced

cancer (Pereira et al Topics in Palliative Care Vol 4 New York

Oxford University Press 2000)

bull haemoptysis

bull haematemesis

bull haematocheziamelaena

bull vaginal bleeding

bull haematuria

bull bleeding in ulcerated skin lesions

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 52

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Mechanisms of haemostatic radiotherapy

bull Sparse literature

bull Coagulation activationsup1

ndash Oxydative endothelial damage

ndash Activation of thrombocytes

ndash Activation of inflammation

bull Long term anti-angiogenetic

sup1 Hallahan et al Oncology (Huntingt) 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 53

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Prostate cancer

bull Reduction of pain and bleeding in hormone refractory

prostate cancer (Kynaston Br J Urol 1990 Kawakami Nippon

Hinyokika Gakkai Zasshi 1993 Kalapurakal Int J Radiat Oncol Biol Phys

2003)

bull 100 improvement in patients with important hematuria (Carlton J Urol 1972)

Bladder cancer (Srinivasan et al Clin Oncol (R Coll Radiol) 1994)

bull 17 Gy in 2 fractions3 days 59 clearance of hematuria

bull 45 Gy in 12 fractions26 days 16 clearance of

hematuria

bull Selection by performance status Palliation (pain and

hematuria) better with hypofractionated RT worse

survival

bull No important side effects

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 54

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung cancer

bull Control of hemoptysis in up to 80 of patients (Brundage

Can J Oncol 1996 Medical Research Council Lung Cancer Working Party

Br J Cancer 1992 Hoskin in Doyle et al Second Edition New York

Oxford University Press 1998 Langendijk Int J Radiat Oncol Biol Phys

2000)

bull Optimal dosefractionation

ndash Hypofractionated RT seems to be equally effective to multiple

fractions (Rees Clin Oncol (R Coll Radiol) 1997 Sundstrom JCO

2004 Phase III Stevens Australas Radiol 1995 Phase III studies of

the MRC (s above)

ndash 10 Gy Single fraction equally effective to multiple fractions less

toxic (Hoskin in Doyle et al Second Edition New York Oxford

University Press 1998 Medical Research Council Lung Cancer

Working Party Br J Cancer 1992)

ndash Mostly total dose of around 20 Gy (multiple fractions) or 8 Gy

single fraction recommended

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 55

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Van Lonkhuijzen

Radiother Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 56

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gynaecologic tumours

bull Cf review van Lonkhuijzen Radiother Oncol 2011

bull Consider intracavitary HDR brachytherapy

Rectal cancer

bull Up to 85 control of rectal bleeding (Hoskin in Doyle et al Second Edition New York Oxford University Press 1998)

Kaposi sarcoma

bull Good palliation for pain bleeding or edema TD 15-40 Gy SD 2 Gy gt90 response 70 complete remission (Review Becker et al Onkologie 2006)

Skin tumours (Miller in Doyle Oxford Textbook of Palliative Medicine New York Oxford University Press 1993)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 57

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duration of treatment effect

Lung cancer

bull Median duration of palliation 50 of remaining life span (30 Gy10d

27 Gy6d 17 Gy2 fract1w apart) (Medical Research Council Br J

Cancer 1991)

bull 1 fract 10 Gy vs 2 fract 85 Gy more patients need repeat RT (Medical Research Council Lung Cancer Working Party Br J Cancer 1992)

bull 417 pat need repeat RT within 3 m after 1x10 Gy (Scolaro Radiol

Med 1995)

Rec ovarian cancer

bull Median duration of palliation 4 m in 90 of patients until death (Corn Cancer 1994)

Cervical endometrial cancer

bull In 50 of patients pall Effect until death with 1-2x10 Gy

ndash Halle IJROBP 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 58

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull RT effective for improvement of

ndashThoracic symptoms (haemoptysis cough thoracic pain

dyspnoea airway obstruction) (Sirzeacuten Acta Oncol 2003 and others)

ndashQOL in about 13 of patients (Langendijk IJROBP 2000)

RT schedules

bull Systematic review (Fairchild JCO 264001-4011 2008)

ndash13 randomized trials 3473 patients

ndashdifferent RT schedules

ndashAim find optimal RT schedule for maximal palliation with

minimal toxicityneed for reirradiation

Thoracic symptoms

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 59

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz

Cancer

2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 60

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz Chow Hartsell Konski Cancer 2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 61

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemoptysis

bull Fig2 toux

733 689

812 802

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 62

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig3 doul thor 321 279

535 482

Cough

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 63

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 4 overall symptom burden

575 519

648 638

Thoracic pain

Fairchild JCO 2008

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 5 survie 1a

Cutoff (sensitivity analysis) BED[10] 35Gy vs LD

100 162

555 609

Overall symptom burden

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 65

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cutoff BED[10] 35Gy vs LD

265 217

Overall survival at 1y

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 66

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 7 Tox dysphagie

Cutoff BED[10] 30Gy vs LD

205 149

about x 2

Toxicity (dysphagia)

Fairchild JCO 2008

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomized trial 250 patients (Falk BMJ 2002)

bull Locally advanced non resectable NSCLC with minimal thoracic symptoms

bull Immediate vs delayed RT (at symptom onset)

bull In delayed arm 56 of patients died without RT

bull No difference in QOL odr OS

bull More acute toxicity in immediate RT arm

Randomized trial (Sundstrom Radiother Oncol 2005)

bull Advanced NSCLC

bull 2 RT schedules (5x4Gy vs 2x85 Gy) immediate RT

bull Stratification according to presenceabsence of thoracic symptoms

bull In asymptomatic patients no long term symptom control but important dysphagia

Timing

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull in 97 malignant

bull in 5-10 of lung cancer patients

bull Histology (exclude benign disease RT-chemosensible tumours

bull Generally spontanous improvement of symptoms by formation of collaterals

Superior vena cava syndrome

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Treatment

1 symptomatic

bull steroids

bull diuretics

bull Elevation of headthorax

2 causal bull chemotherapy (SCLC

lymphomas germinal tumours)

bull Endovascular stent placement

bull radiotherapy Palliative care in lung cancer ACCP

evidence- based clinical practice guidelines

(2nd edition)

Kvale Chest 2007

Superior vena cava syndrome

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

Radiotherapy

bull Mostly clinical response within 72 h

bull Complete clinical response at 2 w in 78 of patients with SCLC

and 63 of patients with NSCLC

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duhamel Atlas clinique des maladies

des voies aeacuteriennes Elsevier

wwwupmccancercenterscom

Endobronchial brachytherapy

Cochrane analysis (Cardona The Cochrane

Library 2008)

bull No improved

symptom relief by

addition of

endobronchial

brachytherapy to

EBRT

bull Indicated in selected

patients pretreated

by EBRT with

central

endobronchial

obstruction

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Ozkok Lung Cancer 2008

Endobronchial brachytherapy

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Take home lung cancer

Dosefractionation

bull Minimum 10x3 Gy 5xw or equivalent

ndash better symptom control and better overall survival

ndash But more toxicity

bull Short schedule for symptom control and limited toxicity

ndashPoor performance status limited life expectancy

Timing

bull RT at the moment of symptom onset

bull No place for bdquoprophylactic palliative RTldquo according to evidence based guidelines

ndashExceptions

bull Young patient good PS aim of local control

bull Imminent symptoms (superior vena cava syndrome central airway obstruction

Rodrigues Pract Rad Oncol 2011

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

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Homs Eur J CancerLancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

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Randomisierte Studien

Homs Lancet 2004

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Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

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Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

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Scoccianti Radiother Oncol 2012

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Konski Semin Oncol 2005

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Konski Semin Oncol 2005

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Overall

response

rate

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Complete

response

rate

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Retreat

ment

rate

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull EBRT significant palliation of painful bone metastasis in

50-80 of patients complete pain relief in up to 13 of

patients (Chow JCO 2007)

bull Optimal fractionation RT technique combination with other

treatment options

bull Systematic review combined with expert opinions

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 23

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Uncomplicated bone

metastasis

Single vs multiple

fractions

bull Pain relief

equivalent

bull Long term toxicity

equivalent

bull Single fraction

optimal patient and

caregiver

convenience

bull Retreatment rate

20 vs 8

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 24

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Repeat treatment of painful spinal metastasis

bull Pain relief in 46-80

bull Cave dose to spinal cord

bull Dosefractionation unclear

bull Recommendation prospective trial

Lutz IJROBP 2011

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Comparable fracture risk Chow Clin Oncol 2012

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Comparable risk of

spinal cord

compression

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SBRT of spinal metastasis

bull Mostly retrospective single-institution series

bull Recommendation prospective trial

bull Not primary treatment for spinal met causing spinal cord

compression

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 28

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Radionuclides

bull Important often underused option for multifocal bone

metastasis

bull For osteoblastic metastasis

bull Based on available data do not obviate need for EBRT

bull Recommendation prospective studies on prophylactic use

of radiopharmaceuticals in patients with limited bone

metastases combination with other systemic agents

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 29

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 30

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Biphosphonates

bull Several prospective studies on concurrent EBRT and

biphosphonates successful pain relief promotion of re-

ossification of damaged bone acceptable risk of toxicity

bull Not shown that combination better than EBRT alone for

pain relief

bull Recommendation prospective trial on optimum RT

fractionation EBRT versus radionuclides dose and

duration of biphosphonates and scheduling

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 31

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 32

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Denosumab

Lipton Curr Opp Supp Pall Care 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 33

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lipton Curr Opp Supp

Pall Care 2011

Denosumab versus

Zoledronate

Prevention of SREs (path fracture RT or OP to bone

spinal cord compression)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 34

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Breast

superior

Prostate

superior

Other solid

tumors or

multiple

myeloma

non inferior

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 35

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Vertebroplastykyphoplasty

bull No prospective data to suggest

that vertkyph obviates the

need for EBRT in painful bone

met

bull Small series of patients treated

by vertkyph plus EBRT

bull Recommendation prospective

trials on patient selection

efficacy toxicity and timing of

vertkyph and RT

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 36

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 37

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Non inferiority study

bull 272 patients randomized

Neuropathic pain

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 38

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 39

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 40

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Spinal cord compression

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 41

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 42

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 43

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Patchell Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 44

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

RT short versus

long course

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 45

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 46

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 47

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 48

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 49

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 50

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull SRO tutorial CNS PD Dr A Pica

bull ScocciantiRicardi Radiother Oncol 2012 Review

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 51

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemorrhage

bull Bleeding in 6-10 of patients with advanced

cancer (Pereira et al Topics in Palliative Care Vol 4 New York

Oxford University Press 2000)

bull haemoptysis

bull haematemesis

bull haematocheziamelaena

bull vaginal bleeding

bull haematuria

bull bleeding in ulcerated skin lesions

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 52

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Mechanisms of haemostatic radiotherapy

bull Sparse literature

bull Coagulation activationsup1

ndash Oxydative endothelial damage

ndash Activation of thrombocytes

ndash Activation of inflammation

bull Long term anti-angiogenetic

sup1 Hallahan et al Oncology (Huntingt) 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 53

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Prostate cancer

bull Reduction of pain and bleeding in hormone refractory

prostate cancer (Kynaston Br J Urol 1990 Kawakami Nippon

Hinyokika Gakkai Zasshi 1993 Kalapurakal Int J Radiat Oncol Biol Phys

2003)

bull 100 improvement in patients with important hematuria (Carlton J Urol 1972)

Bladder cancer (Srinivasan et al Clin Oncol (R Coll Radiol) 1994)

bull 17 Gy in 2 fractions3 days 59 clearance of hematuria

bull 45 Gy in 12 fractions26 days 16 clearance of

hematuria

bull Selection by performance status Palliation (pain and

hematuria) better with hypofractionated RT worse

survival

bull No important side effects

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 54

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung cancer

bull Control of hemoptysis in up to 80 of patients (Brundage

Can J Oncol 1996 Medical Research Council Lung Cancer Working Party

Br J Cancer 1992 Hoskin in Doyle et al Second Edition New York

Oxford University Press 1998 Langendijk Int J Radiat Oncol Biol Phys

2000)

bull Optimal dosefractionation

ndash Hypofractionated RT seems to be equally effective to multiple

fractions (Rees Clin Oncol (R Coll Radiol) 1997 Sundstrom JCO

2004 Phase III Stevens Australas Radiol 1995 Phase III studies of

the MRC (s above)

ndash 10 Gy Single fraction equally effective to multiple fractions less

toxic (Hoskin in Doyle et al Second Edition New York Oxford

University Press 1998 Medical Research Council Lung Cancer

Working Party Br J Cancer 1992)

ndash Mostly total dose of around 20 Gy (multiple fractions) or 8 Gy

single fraction recommended

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 55

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Van Lonkhuijzen

Radiother Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 56

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gynaecologic tumours

bull Cf review van Lonkhuijzen Radiother Oncol 2011

bull Consider intracavitary HDR brachytherapy

Rectal cancer

bull Up to 85 control of rectal bleeding (Hoskin in Doyle et al Second Edition New York Oxford University Press 1998)

Kaposi sarcoma

bull Good palliation for pain bleeding or edema TD 15-40 Gy SD 2 Gy gt90 response 70 complete remission (Review Becker et al Onkologie 2006)

Skin tumours (Miller in Doyle Oxford Textbook of Palliative Medicine New York Oxford University Press 1993)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 57

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duration of treatment effect

Lung cancer

bull Median duration of palliation 50 of remaining life span (30 Gy10d

27 Gy6d 17 Gy2 fract1w apart) (Medical Research Council Br J

Cancer 1991)

bull 1 fract 10 Gy vs 2 fract 85 Gy more patients need repeat RT (Medical Research Council Lung Cancer Working Party Br J Cancer 1992)

bull 417 pat need repeat RT within 3 m after 1x10 Gy (Scolaro Radiol

Med 1995)

Rec ovarian cancer

bull Median duration of palliation 4 m in 90 of patients until death (Corn Cancer 1994)

Cervical endometrial cancer

bull In 50 of patients pall Effect until death with 1-2x10 Gy

ndash Halle IJROBP 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 58

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull RT effective for improvement of

ndashThoracic symptoms (haemoptysis cough thoracic pain

dyspnoea airway obstruction) (Sirzeacuten Acta Oncol 2003 and others)

ndashQOL in about 13 of patients (Langendijk IJROBP 2000)

RT schedules

bull Systematic review (Fairchild JCO 264001-4011 2008)

ndash13 randomized trials 3473 patients

ndashdifferent RT schedules

ndashAim find optimal RT schedule for maximal palliation with

minimal toxicityneed for reirradiation

Thoracic symptoms

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 59

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz

Cancer

2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 60

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz Chow Hartsell Konski Cancer 2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 61

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemoptysis

bull Fig2 toux

733 689

812 802

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 62

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig3 doul thor 321 279

535 482

Cough

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 63

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 4 overall symptom burden

575 519

648 638

Thoracic pain

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 64

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 5 survie 1a

Cutoff (sensitivity analysis) BED[10] 35Gy vs LD

100 162

555 609

Overall symptom burden

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 65

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cutoff BED[10] 35Gy vs LD

265 217

Overall survival at 1y

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 66

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 7 Tox dysphagie

Cutoff BED[10] 30Gy vs LD

205 149

about x 2

Toxicity (dysphagia)

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 67

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomized trial 250 patients (Falk BMJ 2002)

bull Locally advanced non resectable NSCLC with minimal thoracic symptoms

bull Immediate vs delayed RT (at symptom onset)

bull In delayed arm 56 of patients died without RT

bull No difference in QOL odr OS

bull More acute toxicity in immediate RT arm

Randomized trial (Sundstrom Radiother Oncol 2005)

bull Advanced NSCLC

bull 2 RT schedules (5x4Gy vs 2x85 Gy) immediate RT

bull Stratification according to presenceabsence of thoracic symptoms

bull In asymptomatic patients no long term symptom control but important dysphagia

Timing

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull in 97 malignant

bull in 5-10 of lung cancer patients

bull Histology (exclude benign disease RT-chemosensible tumours

bull Generally spontanous improvement of symptoms by formation of collaterals

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 69

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Treatment

1 symptomatic

bull steroids

bull diuretics

bull Elevation of headthorax

2 causal bull chemotherapy (SCLC

lymphomas germinal tumours)

bull Endovascular stent placement

bull radiotherapy Palliative care in lung cancer ACCP

evidence- based clinical practice guidelines

(2nd edition)

Kvale Chest 2007

Superior vena cava syndrome

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

Radiotherapy

bull Mostly clinical response within 72 h

bull Complete clinical response at 2 w in 78 of patients with SCLC

and 63 of patients with NSCLC

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duhamel Atlas clinique des maladies

des voies aeacuteriennes Elsevier

wwwupmccancercenterscom

Endobronchial brachytherapy

Cochrane analysis (Cardona The Cochrane

Library 2008)

bull No improved

symptom relief by

addition of

endobronchial

brachytherapy to

EBRT

bull Indicated in selected

patients pretreated

by EBRT with

central

endobronchial

obstruction

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Ozkok Lung Cancer 2008

Endobronchial brachytherapy

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Take home lung cancer

Dosefractionation

bull Minimum 10x3 Gy 5xw or equivalent

ndash better symptom control and better overall survival

ndash But more toxicity

bull Short schedule for symptom control and limited toxicity

ndashPoor performance status limited life expectancy

Timing

bull RT at the moment of symptom onset

bull No place for bdquoprophylactic palliative RTldquo according to evidence based guidelines

ndashExceptions

bull Young patient good PS aim of local control

bull Imminent symptoms (superior vena cava syndrome central airway obstruction

Rodrigues Pract Rad Oncol 2011

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 80

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

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Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 82

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

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Scoccianti Radiother Oncol 2012

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Page 18: SRO Tutorial Palliative Care 04.05.2012 Palliative Radiotherapy · 2018-02-22 · SRO Tutorial Palliative Care – Palliative Radiotherapy 30 Jacqueline Vock, Universitätsklinik

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Konski Semin Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 19

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Overall

response

rate

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Complete

response

rate

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Retreat

ment

rate

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull EBRT significant palliation of painful bone metastasis in

50-80 of patients complete pain relief in up to 13 of

patients (Chow JCO 2007)

bull Optimal fractionation RT technique combination with other

treatment options

bull Systematic review combined with expert opinions

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 23

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Uncomplicated bone

metastasis

Single vs multiple

fractions

bull Pain relief

equivalent

bull Long term toxicity

equivalent

bull Single fraction

optimal patient and

caregiver

convenience

bull Retreatment rate

20 vs 8

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 24

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Repeat treatment of painful spinal metastasis

bull Pain relief in 46-80

bull Cave dose to spinal cord

bull Dosefractionation unclear

bull Recommendation prospective trial

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 25

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Comparable fracture risk Chow Clin Oncol 2012

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 26

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Comparable risk of

spinal cord

compression

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 27

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SBRT of spinal metastasis

bull Mostly retrospective single-institution series

bull Recommendation prospective trial

bull Not primary treatment for spinal met causing spinal cord

compression

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 28

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Radionuclides

bull Important often underused option for multifocal bone

metastasis

bull For osteoblastic metastasis

bull Based on available data do not obviate need for EBRT

bull Recommendation prospective studies on prophylactic use

of radiopharmaceuticals in patients with limited bone

metastases combination with other systemic agents

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 29

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 30

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Biphosphonates

bull Several prospective studies on concurrent EBRT and

biphosphonates successful pain relief promotion of re-

ossification of damaged bone acceptable risk of toxicity

bull Not shown that combination better than EBRT alone for

pain relief

bull Recommendation prospective trial on optimum RT

fractionation EBRT versus radionuclides dose and

duration of biphosphonates and scheduling

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 31

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 32

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Denosumab

Lipton Curr Opp Supp Pall Care 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 33

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lipton Curr Opp Supp

Pall Care 2011

Denosumab versus

Zoledronate

Prevention of SREs (path fracture RT or OP to bone

spinal cord compression)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 34

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Breast

superior

Prostate

superior

Other solid

tumors or

multiple

myeloma

non inferior

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 35

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Vertebroplastykyphoplasty

bull No prospective data to suggest

that vertkyph obviates the

need for EBRT in painful bone

met

bull Small series of patients treated

by vertkyph plus EBRT

bull Recommendation prospective

trials on patient selection

efficacy toxicity and timing of

vertkyph and RT

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 36

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 37

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Non inferiority study

bull 272 patients randomized

Neuropathic pain

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 38

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 39

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 40

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Spinal cord compression

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 41

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 42

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 43

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Patchell Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 44

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

RT short versus

long course

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 45

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 46

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 47

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 48

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 49

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 50

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull SRO tutorial CNS PD Dr A Pica

bull ScocciantiRicardi Radiother Oncol 2012 Review

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 51

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemorrhage

bull Bleeding in 6-10 of patients with advanced

cancer (Pereira et al Topics in Palliative Care Vol 4 New York

Oxford University Press 2000)

bull haemoptysis

bull haematemesis

bull haematocheziamelaena

bull vaginal bleeding

bull haematuria

bull bleeding in ulcerated skin lesions

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 52

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Mechanisms of haemostatic radiotherapy

bull Sparse literature

bull Coagulation activationsup1

ndash Oxydative endothelial damage

ndash Activation of thrombocytes

ndash Activation of inflammation

bull Long term anti-angiogenetic

sup1 Hallahan et al Oncology (Huntingt) 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 53

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Prostate cancer

bull Reduction of pain and bleeding in hormone refractory

prostate cancer (Kynaston Br J Urol 1990 Kawakami Nippon

Hinyokika Gakkai Zasshi 1993 Kalapurakal Int J Radiat Oncol Biol Phys

2003)

bull 100 improvement in patients with important hematuria (Carlton J Urol 1972)

Bladder cancer (Srinivasan et al Clin Oncol (R Coll Radiol) 1994)

bull 17 Gy in 2 fractions3 days 59 clearance of hematuria

bull 45 Gy in 12 fractions26 days 16 clearance of

hematuria

bull Selection by performance status Palliation (pain and

hematuria) better with hypofractionated RT worse

survival

bull No important side effects

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 54

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung cancer

bull Control of hemoptysis in up to 80 of patients (Brundage

Can J Oncol 1996 Medical Research Council Lung Cancer Working Party

Br J Cancer 1992 Hoskin in Doyle et al Second Edition New York

Oxford University Press 1998 Langendijk Int J Radiat Oncol Biol Phys

2000)

bull Optimal dosefractionation

ndash Hypofractionated RT seems to be equally effective to multiple

fractions (Rees Clin Oncol (R Coll Radiol) 1997 Sundstrom JCO

2004 Phase III Stevens Australas Radiol 1995 Phase III studies of

the MRC (s above)

ndash 10 Gy Single fraction equally effective to multiple fractions less

toxic (Hoskin in Doyle et al Second Edition New York Oxford

University Press 1998 Medical Research Council Lung Cancer

Working Party Br J Cancer 1992)

ndash Mostly total dose of around 20 Gy (multiple fractions) or 8 Gy

single fraction recommended

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 55

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Van Lonkhuijzen

Radiother Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 56

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gynaecologic tumours

bull Cf review van Lonkhuijzen Radiother Oncol 2011

bull Consider intracavitary HDR brachytherapy

Rectal cancer

bull Up to 85 control of rectal bleeding (Hoskin in Doyle et al Second Edition New York Oxford University Press 1998)

Kaposi sarcoma

bull Good palliation for pain bleeding or edema TD 15-40 Gy SD 2 Gy gt90 response 70 complete remission (Review Becker et al Onkologie 2006)

Skin tumours (Miller in Doyle Oxford Textbook of Palliative Medicine New York Oxford University Press 1993)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 57

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duration of treatment effect

Lung cancer

bull Median duration of palliation 50 of remaining life span (30 Gy10d

27 Gy6d 17 Gy2 fract1w apart) (Medical Research Council Br J

Cancer 1991)

bull 1 fract 10 Gy vs 2 fract 85 Gy more patients need repeat RT (Medical Research Council Lung Cancer Working Party Br J Cancer 1992)

bull 417 pat need repeat RT within 3 m after 1x10 Gy (Scolaro Radiol

Med 1995)

Rec ovarian cancer

bull Median duration of palliation 4 m in 90 of patients until death (Corn Cancer 1994)

Cervical endometrial cancer

bull In 50 of patients pall Effect until death with 1-2x10 Gy

ndash Halle IJROBP 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 58

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull RT effective for improvement of

ndashThoracic symptoms (haemoptysis cough thoracic pain

dyspnoea airway obstruction) (Sirzeacuten Acta Oncol 2003 and others)

ndashQOL in about 13 of patients (Langendijk IJROBP 2000)

RT schedules

bull Systematic review (Fairchild JCO 264001-4011 2008)

ndash13 randomized trials 3473 patients

ndashdifferent RT schedules

ndashAim find optimal RT schedule for maximal palliation with

minimal toxicityneed for reirradiation

Thoracic symptoms

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 59

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz

Cancer

2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 60

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz Chow Hartsell Konski Cancer 2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 61

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemoptysis

bull Fig2 toux

733 689

812 802

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 62

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig3 doul thor 321 279

535 482

Cough

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 63

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 4 overall symptom burden

575 519

648 638

Thoracic pain

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 64

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 5 survie 1a

Cutoff (sensitivity analysis) BED[10] 35Gy vs LD

100 162

555 609

Overall symptom burden

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 65

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cutoff BED[10] 35Gy vs LD

265 217

Overall survival at 1y

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 66

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 7 Tox dysphagie

Cutoff BED[10] 30Gy vs LD

205 149

about x 2

Toxicity (dysphagia)

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 67

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomized trial 250 patients (Falk BMJ 2002)

bull Locally advanced non resectable NSCLC with minimal thoracic symptoms

bull Immediate vs delayed RT (at symptom onset)

bull In delayed arm 56 of patients died without RT

bull No difference in QOL odr OS

bull More acute toxicity in immediate RT arm

Randomized trial (Sundstrom Radiother Oncol 2005)

bull Advanced NSCLC

bull 2 RT schedules (5x4Gy vs 2x85 Gy) immediate RT

bull Stratification according to presenceabsence of thoracic symptoms

bull In asymptomatic patients no long term symptom control but important dysphagia

Timing

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 68

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull in 97 malignant

bull in 5-10 of lung cancer patients

bull Histology (exclude benign disease RT-chemosensible tumours

bull Generally spontanous improvement of symptoms by formation of collaterals

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 69

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Treatment

1 symptomatic

bull steroids

bull diuretics

bull Elevation of headthorax

2 causal bull chemotherapy (SCLC

lymphomas germinal tumours)

bull Endovascular stent placement

bull radiotherapy Palliative care in lung cancer ACCP

evidence- based clinical practice guidelines

(2nd edition)

Kvale Chest 2007

Superior vena cava syndrome

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

Radiotherapy

bull Mostly clinical response within 72 h

bull Complete clinical response at 2 w in 78 of patients with SCLC

and 63 of patients with NSCLC

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 73

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duhamel Atlas clinique des maladies

des voies aeacuteriennes Elsevier

wwwupmccancercenterscom

Endobronchial brachytherapy

Cochrane analysis (Cardona The Cochrane

Library 2008)

bull No improved

symptom relief by

addition of

endobronchial

brachytherapy to

EBRT

bull Indicated in selected

patients pretreated

by EBRT with

central

endobronchial

obstruction

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 74

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Ozkok Lung Cancer 2008

Endobronchial brachytherapy

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Take home lung cancer

Dosefractionation

bull Minimum 10x3 Gy 5xw or equivalent

ndash better symptom control and better overall survival

ndash But more toxicity

bull Short schedule for symptom control and limited toxicity

ndashPoor performance status limited life expectancy

Timing

bull RT at the moment of symptom onset

bull No place for bdquoprophylactic palliative RTldquo according to evidence based guidelines

ndashExceptions

bull Young patient good PS aim of local control

bull Imminent symptoms (superior vena cava syndrome central airway obstruction

Rodrigues Pract Rad Oncol 2011

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SRO Tutorial Palliative Care ndash Palliative Radiotherapy 77

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 80

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 82

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 83

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

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Scoccianti Radiother Oncol 2012

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 102

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 103

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 104

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Page 19: SRO Tutorial Palliative Care 04.05.2012 Palliative Radiotherapy · 2018-02-22 · SRO Tutorial Palliative Care – Palliative Radiotherapy 30 Jacqueline Vock, Universitätsklinik

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Overall

response

rate

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Complete

response

rate

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Retreat

ment

rate

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 22

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull EBRT significant palliation of painful bone metastasis in

50-80 of patients complete pain relief in up to 13 of

patients (Chow JCO 2007)

bull Optimal fractionation RT technique combination with other

treatment options

bull Systematic review combined with expert opinions

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 23

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Uncomplicated bone

metastasis

Single vs multiple

fractions

bull Pain relief

equivalent

bull Long term toxicity

equivalent

bull Single fraction

optimal patient and

caregiver

convenience

bull Retreatment rate

20 vs 8

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 24

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Repeat treatment of painful spinal metastasis

bull Pain relief in 46-80

bull Cave dose to spinal cord

bull Dosefractionation unclear

bull Recommendation prospective trial

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 25

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Comparable fracture risk Chow Clin Oncol 2012

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 26

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Comparable risk of

spinal cord

compression

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 27

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SBRT of spinal metastasis

bull Mostly retrospective single-institution series

bull Recommendation prospective trial

bull Not primary treatment for spinal met causing spinal cord

compression

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 28

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Radionuclides

bull Important often underused option for multifocal bone

metastasis

bull For osteoblastic metastasis

bull Based on available data do not obviate need for EBRT

bull Recommendation prospective studies on prophylactic use

of radiopharmaceuticals in patients with limited bone

metastases combination with other systemic agents

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 29

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 30

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Biphosphonates

bull Several prospective studies on concurrent EBRT and

biphosphonates successful pain relief promotion of re-

ossification of damaged bone acceptable risk of toxicity

bull Not shown that combination better than EBRT alone for

pain relief

bull Recommendation prospective trial on optimum RT

fractionation EBRT versus radionuclides dose and

duration of biphosphonates and scheduling

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 31

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 32

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Denosumab

Lipton Curr Opp Supp Pall Care 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 33

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lipton Curr Opp Supp

Pall Care 2011

Denosumab versus

Zoledronate

Prevention of SREs (path fracture RT or OP to bone

spinal cord compression)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 34

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Breast

superior

Prostate

superior

Other solid

tumors or

multiple

myeloma

non inferior

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 35

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Vertebroplastykyphoplasty

bull No prospective data to suggest

that vertkyph obviates the

need for EBRT in painful bone

met

bull Small series of patients treated

by vertkyph plus EBRT

bull Recommendation prospective

trials on patient selection

efficacy toxicity and timing of

vertkyph and RT

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 36

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 37

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Non inferiority study

bull 272 patients randomized

Neuropathic pain

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 38

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 39

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 40

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Spinal cord compression

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 41

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 42

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 43

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Patchell Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 44

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

RT short versus

long course

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 45

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 46

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 47

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 48

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 49

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 50

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull SRO tutorial CNS PD Dr A Pica

bull ScocciantiRicardi Radiother Oncol 2012 Review

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 51

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemorrhage

bull Bleeding in 6-10 of patients with advanced

cancer (Pereira et al Topics in Palliative Care Vol 4 New York

Oxford University Press 2000)

bull haemoptysis

bull haematemesis

bull haematocheziamelaena

bull vaginal bleeding

bull haematuria

bull bleeding in ulcerated skin lesions

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 52

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Mechanisms of haemostatic radiotherapy

bull Sparse literature

bull Coagulation activationsup1

ndash Oxydative endothelial damage

ndash Activation of thrombocytes

ndash Activation of inflammation

bull Long term anti-angiogenetic

sup1 Hallahan et al Oncology (Huntingt) 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 53

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Prostate cancer

bull Reduction of pain and bleeding in hormone refractory

prostate cancer (Kynaston Br J Urol 1990 Kawakami Nippon

Hinyokika Gakkai Zasshi 1993 Kalapurakal Int J Radiat Oncol Biol Phys

2003)

bull 100 improvement in patients with important hematuria (Carlton J Urol 1972)

Bladder cancer (Srinivasan et al Clin Oncol (R Coll Radiol) 1994)

bull 17 Gy in 2 fractions3 days 59 clearance of hematuria

bull 45 Gy in 12 fractions26 days 16 clearance of

hematuria

bull Selection by performance status Palliation (pain and

hematuria) better with hypofractionated RT worse

survival

bull No important side effects

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 54

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung cancer

bull Control of hemoptysis in up to 80 of patients (Brundage

Can J Oncol 1996 Medical Research Council Lung Cancer Working Party

Br J Cancer 1992 Hoskin in Doyle et al Second Edition New York

Oxford University Press 1998 Langendijk Int J Radiat Oncol Biol Phys

2000)

bull Optimal dosefractionation

ndash Hypofractionated RT seems to be equally effective to multiple

fractions (Rees Clin Oncol (R Coll Radiol) 1997 Sundstrom JCO

2004 Phase III Stevens Australas Radiol 1995 Phase III studies of

the MRC (s above)

ndash 10 Gy Single fraction equally effective to multiple fractions less

toxic (Hoskin in Doyle et al Second Edition New York Oxford

University Press 1998 Medical Research Council Lung Cancer

Working Party Br J Cancer 1992)

ndash Mostly total dose of around 20 Gy (multiple fractions) or 8 Gy

single fraction recommended

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 55

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Van Lonkhuijzen

Radiother Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 56

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gynaecologic tumours

bull Cf review van Lonkhuijzen Radiother Oncol 2011

bull Consider intracavitary HDR brachytherapy

Rectal cancer

bull Up to 85 control of rectal bleeding (Hoskin in Doyle et al Second Edition New York Oxford University Press 1998)

Kaposi sarcoma

bull Good palliation for pain bleeding or edema TD 15-40 Gy SD 2 Gy gt90 response 70 complete remission (Review Becker et al Onkologie 2006)

Skin tumours (Miller in Doyle Oxford Textbook of Palliative Medicine New York Oxford University Press 1993)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 57

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duration of treatment effect

Lung cancer

bull Median duration of palliation 50 of remaining life span (30 Gy10d

27 Gy6d 17 Gy2 fract1w apart) (Medical Research Council Br J

Cancer 1991)

bull 1 fract 10 Gy vs 2 fract 85 Gy more patients need repeat RT (Medical Research Council Lung Cancer Working Party Br J Cancer 1992)

bull 417 pat need repeat RT within 3 m after 1x10 Gy (Scolaro Radiol

Med 1995)

Rec ovarian cancer

bull Median duration of palliation 4 m in 90 of patients until death (Corn Cancer 1994)

Cervical endometrial cancer

bull In 50 of patients pall Effect until death with 1-2x10 Gy

ndash Halle IJROBP 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 58

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull RT effective for improvement of

ndashThoracic symptoms (haemoptysis cough thoracic pain

dyspnoea airway obstruction) (Sirzeacuten Acta Oncol 2003 and others)

ndashQOL in about 13 of patients (Langendijk IJROBP 2000)

RT schedules

bull Systematic review (Fairchild JCO 264001-4011 2008)

ndash13 randomized trials 3473 patients

ndashdifferent RT schedules

ndashAim find optimal RT schedule for maximal palliation with

minimal toxicityneed for reirradiation

Thoracic symptoms

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 59

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz

Cancer

2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 60

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz Chow Hartsell Konski Cancer 2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 61

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemoptysis

bull Fig2 toux

733 689

812 802

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 62

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig3 doul thor 321 279

535 482

Cough

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 63

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 4 overall symptom burden

575 519

648 638

Thoracic pain

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 64

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 5 survie 1a

Cutoff (sensitivity analysis) BED[10] 35Gy vs LD

100 162

555 609

Overall symptom burden

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 65

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cutoff BED[10] 35Gy vs LD

265 217

Overall survival at 1y

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 66

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 7 Tox dysphagie

Cutoff BED[10] 30Gy vs LD

205 149

about x 2

Toxicity (dysphagia)

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 67

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomized trial 250 patients (Falk BMJ 2002)

bull Locally advanced non resectable NSCLC with minimal thoracic symptoms

bull Immediate vs delayed RT (at symptom onset)

bull In delayed arm 56 of patients died without RT

bull No difference in QOL odr OS

bull More acute toxicity in immediate RT arm

Randomized trial (Sundstrom Radiother Oncol 2005)

bull Advanced NSCLC

bull 2 RT schedules (5x4Gy vs 2x85 Gy) immediate RT

bull Stratification according to presenceabsence of thoracic symptoms

bull In asymptomatic patients no long term symptom control but important dysphagia

Timing

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 68

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull in 97 malignant

bull in 5-10 of lung cancer patients

bull Histology (exclude benign disease RT-chemosensible tumours

bull Generally spontanous improvement of symptoms by formation of collaterals

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 69

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Treatment

1 symptomatic

bull steroids

bull diuretics

bull Elevation of headthorax

2 causal bull chemotherapy (SCLC

lymphomas germinal tumours)

bull Endovascular stent placement

bull radiotherapy Palliative care in lung cancer ACCP

evidence- based clinical practice guidelines

(2nd edition)

Kvale Chest 2007

Superior vena cava syndrome

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

Radiotherapy

bull Mostly clinical response within 72 h

bull Complete clinical response at 2 w in 78 of patients with SCLC

and 63 of patients with NSCLC

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 72

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 73

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duhamel Atlas clinique des maladies

des voies aeacuteriennes Elsevier

wwwupmccancercenterscom

Endobronchial brachytherapy

Cochrane analysis (Cardona The Cochrane

Library 2008)

bull No improved

symptom relief by

addition of

endobronchial

brachytherapy to

EBRT

bull Indicated in selected

patients pretreated

by EBRT with

central

endobronchial

obstruction

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 74

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Ozkok Lung Cancer 2008

Endobronchial brachytherapy

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Take home lung cancer

Dosefractionation

bull Minimum 10x3 Gy 5xw or equivalent

ndash better symptom control and better overall survival

ndash But more toxicity

bull Short schedule for symptom control and limited toxicity

ndashPoor performance status limited life expectancy

Timing

bull RT at the moment of symptom onset

bull No place for bdquoprophylactic palliative RTldquo according to evidence based guidelines

ndashExceptions

bull Young patient good PS aim of local control

bull Imminent symptoms (superior vena cava syndrome central airway obstruction

Rodrigues Pract Rad Oncol 2011

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Homs Eur J CancerLancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

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Randomisierte Studien

Homs Lancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

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Scoccianti Radiother Oncol 2012

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SRO Tutorial Palliative Care ndash Palliative Radiotherapy 101

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 102

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 103

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Complete

response

rate

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Retreat

ment

rate

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull EBRT significant palliation of painful bone metastasis in

50-80 of patients complete pain relief in up to 13 of

patients (Chow JCO 2007)

bull Optimal fractionation RT technique combination with other

treatment options

bull Systematic review combined with expert opinions

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 23

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Uncomplicated bone

metastasis

Single vs multiple

fractions

bull Pain relief

equivalent

bull Long term toxicity

equivalent

bull Single fraction

optimal patient and

caregiver

convenience

bull Retreatment rate

20 vs 8

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 24

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Repeat treatment of painful spinal metastasis

bull Pain relief in 46-80

bull Cave dose to spinal cord

bull Dosefractionation unclear

bull Recommendation prospective trial

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 25

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Comparable fracture risk Chow Clin Oncol 2012

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 26

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Comparable risk of

spinal cord

compression

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 27

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SBRT of spinal metastasis

bull Mostly retrospective single-institution series

bull Recommendation prospective trial

bull Not primary treatment for spinal met causing spinal cord

compression

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 28

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Radionuclides

bull Important often underused option for multifocal bone

metastasis

bull For osteoblastic metastasis

bull Based on available data do not obviate need for EBRT

bull Recommendation prospective studies on prophylactic use

of radiopharmaceuticals in patients with limited bone

metastases combination with other systemic agents

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 29

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 30

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Biphosphonates

bull Several prospective studies on concurrent EBRT and

biphosphonates successful pain relief promotion of re-

ossification of damaged bone acceptable risk of toxicity

bull Not shown that combination better than EBRT alone for

pain relief

bull Recommendation prospective trial on optimum RT

fractionation EBRT versus radionuclides dose and

duration of biphosphonates and scheduling

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 31

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 32

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Denosumab

Lipton Curr Opp Supp Pall Care 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 33

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lipton Curr Opp Supp

Pall Care 2011

Denosumab versus

Zoledronate

Prevention of SREs (path fracture RT or OP to bone

spinal cord compression)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 34

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Breast

superior

Prostate

superior

Other solid

tumors or

multiple

myeloma

non inferior

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 35

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Vertebroplastykyphoplasty

bull No prospective data to suggest

that vertkyph obviates the

need for EBRT in painful bone

met

bull Small series of patients treated

by vertkyph plus EBRT

bull Recommendation prospective

trials on patient selection

efficacy toxicity and timing of

vertkyph and RT

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 36

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 37

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Non inferiority study

bull 272 patients randomized

Neuropathic pain

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 38

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 39

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 40

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Spinal cord compression

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 41

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 42

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 43

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Patchell Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 44

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

RT short versus

long course

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 45

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 46

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 47

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 48

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 49

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 50

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull SRO tutorial CNS PD Dr A Pica

bull ScocciantiRicardi Radiother Oncol 2012 Review

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 51

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemorrhage

bull Bleeding in 6-10 of patients with advanced

cancer (Pereira et al Topics in Palliative Care Vol 4 New York

Oxford University Press 2000)

bull haemoptysis

bull haematemesis

bull haematocheziamelaena

bull vaginal bleeding

bull haematuria

bull bleeding in ulcerated skin lesions

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 52

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Mechanisms of haemostatic radiotherapy

bull Sparse literature

bull Coagulation activationsup1

ndash Oxydative endothelial damage

ndash Activation of thrombocytes

ndash Activation of inflammation

bull Long term anti-angiogenetic

sup1 Hallahan et al Oncology (Huntingt) 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 53

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Prostate cancer

bull Reduction of pain and bleeding in hormone refractory

prostate cancer (Kynaston Br J Urol 1990 Kawakami Nippon

Hinyokika Gakkai Zasshi 1993 Kalapurakal Int J Radiat Oncol Biol Phys

2003)

bull 100 improvement in patients with important hematuria (Carlton J Urol 1972)

Bladder cancer (Srinivasan et al Clin Oncol (R Coll Radiol) 1994)

bull 17 Gy in 2 fractions3 days 59 clearance of hematuria

bull 45 Gy in 12 fractions26 days 16 clearance of

hematuria

bull Selection by performance status Palliation (pain and

hematuria) better with hypofractionated RT worse

survival

bull No important side effects

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 54

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung cancer

bull Control of hemoptysis in up to 80 of patients (Brundage

Can J Oncol 1996 Medical Research Council Lung Cancer Working Party

Br J Cancer 1992 Hoskin in Doyle et al Second Edition New York

Oxford University Press 1998 Langendijk Int J Radiat Oncol Biol Phys

2000)

bull Optimal dosefractionation

ndash Hypofractionated RT seems to be equally effective to multiple

fractions (Rees Clin Oncol (R Coll Radiol) 1997 Sundstrom JCO

2004 Phase III Stevens Australas Radiol 1995 Phase III studies of

the MRC (s above)

ndash 10 Gy Single fraction equally effective to multiple fractions less

toxic (Hoskin in Doyle et al Second Edition New York Oxford

University Press 1998 Medical Research Council Lung Cancer

Working Party Br J Cancer 1992)

ndash Mostly total dose of around 20 Gy (multiple fractions) or 8 Gy

single fraction recommended

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 55

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Van Lonkhuijzen

Radiother Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 56

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gynaecologic tumours

bull Cf review van Lonkhuijzen Radiother Oncol 2011

bull Consider intracavitary HDR brachytherapy

Rectal cancer

bull Up to 85 control of rectal bleeding (Hoskin in Doyle et al Second Edition New York Oxford University Press 1998)

Kaposi sarcoma

bull Good palliation for pain bleeding or edema TD 15-40 Gy SD 2 Gy gt90 response 70 complete remission (Review Becker et al Onkologie 2006)

Skin tumours (Miller in Doyle Oxford Textbook of Palliative Medicine New York Oxford University Press 1993)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 57

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duration of treatment effect

Lung cancer

bull Median duration of palliation 50 of remaining life span (30 Gy10d

27 Gy6d 17 Gy2 fract1w apart) (Medical Research Council Br J

Cancer 1991)

bull 1 fract 10 Gy vs 2 fract 85 Gy more patients need repeat RT (Medical Research Council Lung Cancer Working Party Br J Cancer 1992)

bull 417 pat need repeat RT within 3 m after 1x10 Gy (Scolaro Radiol

Med 1995)

Rec ovarian cancer

bull Median duration of palliation 4 m in 90 of patients until death (Corn Cancer 1994)

Cervical endometrial cancer

bull In 50 of patients pall Effect until death with 1-2x10 Gy

ndash Halle IJROBP 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 58

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull RT effective for improvement of

ndashThoracic symptoms (haemoptysis cough thoracic pain

dyspnoea airway obstruction) (Sirzeacuten Acta Oncol 2003 and others)

ndashQOL in about 13 of patients (Langendijk IJROBP 2000)

RT schedules

bull Systematic review (Fairchild JCO 264001-4011 2008)

ndash13 randomized trials 3473 patients

ndashdifferent RT schedules

ndashAim find optimal RT schedule for maximal palliation with

minimal toxicityneed for reirradiation

Thoracic symptoms

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 59

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz

Cancer

2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 60

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz Chow Hartsell Konski Cancer 2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 61

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemoptysis

bull Fig2 toux

733 689

812 802

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 62

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig3 doul thor 321 279

535 482

Cough

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 63

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 4 overall symptom burden

575 519

648 638

Thoracic pain

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 64

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 5 survie 1a

Cutoff (sensitivity analysis) BED[10] 35Gy vs LD

100 162

555 609

Overall symptom burden

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 65

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cutoff BED[10] 35Gy vs LD

265 217

Overall survival at 1y

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 66

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 7 Tox dysphagie

Cutoff BED[10] 30Gy vs LD

205 149

about x 2

Toxicity (dysphagia)

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 67

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomized trial 250 patients (Falk BMJ 2002)

bull Locally advanced non resectable NSCLC with minimal thoracic symptoms

bull Immediate vs delayed RT (at symptom onset)

bull In delayed arm 56 of patients died without RT

bull No difference in QOL odr OS

bull More acute toxicity in immediate RT arm

Randomized trial (Sundstrom Radiother Oncol 2005)

bull Advanced NSCLC

bull 2 RT schedules (5x4Gy vs 2x85 Gy) immediate RT

bull Stratification according to presenceabsence of thoracic symptoms

bull In asymptomatic patients no long term symptom control but important dysphagia

Timing

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 68

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull in 97 malignant

bull in 5-10 of lung cancer patients

bull Histology (exclude benign disease RT-chemosensible tumours

bull Generally spontanous improvement of symptoms by formation of collaterals

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 69

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Treatment

1 symptomatic

bull steroids

bull diuretics

bull Elevation of headthorax

2 causal bull chemotherapy (SCLC

lymphomas germinal tumours)

bull Endovascular stent placement

bull radiotherapy Palliative care in lung cancer ACCP

evidence- based clinical practice guidelines

(2nd edition)

Kvale Chest 2007

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 70

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

Radiotherapy

bull Mostly clinical response within 72 h

bull Complete clinical response at 2 w in 78 of patients with SCLC

and 63 of patients with NSCLC

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 72

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 73

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duhamel Atlas clinique des maladies

des voies aeacuteriennes Elsevier

wwwupmccancercenterscom

Endobronchial brachytherapy

Cochrane analysis (Cardona The Cochrane

Library 2008)

bull No improved

symptom relief by

addition of

endobronchial

brachytherapy to

EBRT

bull Indicated in selected

patients pretreated

by EBRT with

central

endobronchial

obstruction

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 74

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Ozkok Lung Cancer 2008

Endobronchial brachytherapy

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Take home lung cancer

Dosefractionation

bull Minimum 10x3 Gy 5xw or equivalent

ndash better symptom control and better overall survival

ndash But more toxicity

bull Short schedule for symptom control and limited toxicity

ndashPoor performance status limited life expectancy

Timing

bull RT at the moment of symptom onset

bull No place for bdquoprophylactic palliative RTldquo according to evidence based guidelines

ndashExceptions

bull Young patient good PS aim of local control

bull Imminent symptoms (superior vena cava syndrome central airway obstruction

Rodrigues Pract Rad Oncol 2011

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 80

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Homs Eur J CancerLancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 84

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

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Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

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Scoccianti Radiother Oncol 2012

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Retreat

ment

rate

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull EBRT significant palliation of painful bone metastasis in

50-80 of patients complete pain relief in up to 13 of

patients (Chow JCO 2007)

bull Optimal fractionation RT technique combination with other

treatment options

bull Systematic review combined with expert opinions

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 23

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Uncomplicated bone

metastasis

Single vs multiple

fractions

bull Pain relief

equivalent

bull Long term toxicity

equivalent

bull Single fraction

optimal patient and

caregiver

convenience

bull Retreatment rate

20 vs 8

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 24

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Repeat treatment of painful spinal metastasis

bull Pain relief in 46-80

bull Cave dose to spinal cord

bull Dosefractionation unclear

bull Recommendation prospective trial

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 25

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Comparable fracture risk Chow Clin Oncol 2012

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 26

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Comparable risk of

spinal cord

compression

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 27

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SBRT of spinal metastasis

bull Mostly retrospective single-institution series

bull Recommendation prospective trial

bull Not primary treatment for spinal met causing spinal cord

compression

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 28

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Radionuclides

bull Important often underused option for multifocal bone

metastasis

bull For osteoblastic metastasis

bull Based on available data do not obviate need for EBRT

bull Recommendation prospective studies on prophylactic use

of radiopharmaceuticals in patients with limited bone

metastases combination with other systemic agents

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 29

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 30

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Biphosphonates

bull Several prospective studies on concurrent EBRT and

biphosphonates successful pain relief promotion of re-

ossification of damaged bone acceptable risk of toxicity

bull Not shown that combination better than EBRT alone for

pain relief

bull Recommendation prospective trial on optimum RT

fractionation EBRT versus radionuclides dose and

duration of biphosphonates and scheduling

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 31

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 32

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Denosumab

Lipton Curr Opp Supp Pall Care 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 33

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lipton Curr Opp Supp

Pall Care 2011

Denosumab versus

Zoledronate

Prevention of SREs (path fracture RT or OP to bone

spinal cord compression)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 34

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Breast

superior

Prostate

superior

Other solid

tumors or

multiple

myeloma

non inferior

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 35

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Vertebroplastykyphoplasty

bull No prospective data to suggest

that vertkyph obviates the

need for EBRT in painful bone

met

bull Small series of patients treated

by vertkyph plus EBRT

bull Recommendation prospective

trials on patient selection

efficacy toxicity and timing of

vertkyph and RT

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 36

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 37

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Non inferiority study

bull 272 patients randomized

Neuropathic pain

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 38

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 39

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 40

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Spinal cord compression

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 41

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 42

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 43

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Patchell Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 44

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

RT short versus

long course

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 45

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 46

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 47

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 48

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 49

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 50

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull SRO tutorial CNS PD Dr A Pica

bull ScocciantiRicardi Radiother Oncol 2012 Review

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 51

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemorrhage

bull Bleeding in 6-10 of patients with advanced

cancer (Pereira et al Topics in Palliative Care Vol 4 New York

Oxford University Press 2000)

bull haemoptysis

bull haematemesis

bull haematocheziamelaena

bull vaginal bleeding

bull haematuria

bull bleeding in ulcerated skin lesions

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 52

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Mechanisms of haemostatic radiotherapy

bull Sparse literature

bull Coagulation activationsup1

ndash Oxydative endothelial damage

ndash Activation of thrombocytes

ndash Activation of inflammation

bull Long term anti-angiogenetic

sup1 Hallahan et al Oncology (Huntingt) 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 53

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Prostate cancer

bull Reduction of pain and bleeding in hormone refractory

prostate cancer (Kynaston Br J Urol 1990 Kawakami Nippon

Hinyokika Gakkai Zasshi 1993 Kalapurakal Int J Radiat Oncol Biol Phys

2003)

bull 100 improvement in patients with important hematuria (Carlton J Urol 1972)

Bladder cancer (Srinivasan et al Clin Oncol (R Coll Radiol) 1994)

bull 17 Gy in 2 fractions3 days 59 clearance of hematuria

bull 45 Gy in 12 fractions26 days 16 clearance of

hematuria

bull Selection by performance status Palliation (pain and

hematuria) better with hypofractionated RT worse

survival

bull No important side effects

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 54

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung cancer

bull Control of hemoptysis in up to 80 of patients (Brundage

Can J Oncol 1996 Medical Research Council Lung Cancer Working Party

Br J Cancer 1992 Hoskin in Doyle et al Second Edition New York

Oxford University Press 1998 Langendijk Int J Radiat Oncol Biol Phys

2000)

bull Optimal dosefractionation

ndash Hypofractionated RT seems to be equally effective to multiple

fractions (Rees Clin Oncol (R Coll Radiol) 1997 Sundstrom JCO

2004 Phase III Stevens Australas Radiol 1995 Phase III studies of

the MRC (s above)

ndash 10 Gy Single fraction equally effective to multiple fractions less

toxic (Hoskin in Doyle et al Second Edition New York Oxford

University Press 1998 Medical Research Council Lung Cancer

Working Party Br J Cancer 1992)

ndash Mostly total dose of around 20 Gy (multiple fractions) or 8 Gy

single fraction recommended

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 55

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Van Lonkhuijzen

Radiother Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 56

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gynaecologic tumours

bull Cf review van Lonkhuijzen Radiother Oncol 2011

bull Consider intracavitary HDR brachytherapy

Rectal cancer

bull Up to 85 control of rectal bleeding (Hoskin in Doyle et al Second Edition New York Oxford University Press 1998)

Kaposi sarcoma

bull Good palliation for pain bleeding or edema TD 15-40 Gy SD 2 Gy gt90 response 70 complete remission (Review Becker et al Onkologie 2006)

Skin tumours (Miller in Doyle Oxford Textbook of Palliative Medicine New York Oxford University Press 1993)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 57

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Duration of treatment effect

Lung cancer

bull Median duration of palliation 50 of remaining life span (30 Gy10d

27 Gy6d 17 Gy2 fract1w apart) (Medical Research Council Br J

Cancer 1991)

bull 1 fract 10 Gy vs 2 fract 85 Gy more patients need repeat RT (Medical Research Council Lung Cancer Working Party Br J Cancer 1992)

bull 417 pat need repeat RT within 3 m after 1x10 Gy (Scolaro Radiol

Med 1995)

Rec ovarian cancer

bull Median duration of palliation 4 m in 90 of patients until death (Corn Cancer 1994)

Cervical endometrial cancer

bull In 50 of patients pall Effect until death with 1-2x10 Gy

ndash Halle IJROBP 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 58

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull RT effective for improvement of

ndashThoracic symptoms (haemoptysis cough thoracic pain

dyspnoea airway obstruction) (Sirzeacuten Acta Oncol 2003 and others)

ndashQOL in about 13 of patients (Langendijk IJROBP 2000)

RT schedules

bull Systematic review (Fairchild JCO 264001-4011 2008)

ndash13 randomized trials 3473 patients

ndashdifferent RT schedules

ndashAim find optimal RT schedule for maximal palliation with

minimal toxicityneed for reirradiation

Thoracic symptoms

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz

Cancer

2007

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz Chow Hartsell Konski Cancer 2007

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Haemoptysis

bull Fig2 toux

733 689

812 802

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 62

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig3 doul thor 321 279

535 482

Cough

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 63

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 4 overall symptom burden

575 519

648 638

Thoracic pain

Fairchild JCO 2008

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 5 survie 1a

Cutoff (sensitivity analysis) BED[10] 35Gy vs LD

100 162

555 609

Overall symptom burden

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 65

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cutoff BED[10] 35Gy vs LD

265 217

Overall survival at 1y

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 66

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 7 Tox dysphagie

Cutoff BED[10] 30Gy vs LD

205 149

about x 2

Toxicity (dysphagia)

Fairchild JCO 2008

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomized trial 250 patients (Falk BMJ 2002)

bull Locally advanced non resectable NSCLC with minimal thoracic symptoms

bull Immediate vs delayed RT (at symptom onset)

bull In delayed arm 56 of patients died without RT

bull No difference in QOL odr OS

bull More acute toxicity in immediate RT arm

Randomized trial (Sundstrom Radiother Oncol 2005)

bull Advanced NSCLC

bull 2 RT schedules (5x4Gy vs 2x85 Gy) immediate RT

bull Stratification according to presenceabsence of thoracic symptoms

bull In asymptomatic patients no long term symptom control but important dysphagia

Timing

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull in 97 malignant

bull in 5-10 of lung cancer patients

bull Histology (exclude benign disease RT-chemosensible tumours

bull Generally spontanous improvement of symptoms by formation of collaterals

Superior vena cava syndrome

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Treatment

1 symptomatic

bull steroids

bull diuretics

bull Elevation of headthorax

2 causal bull chemotherapy (SCLC

lymphomas germinal tumours)

bull Endovascular stent placement

bull radiotherapy Palliative care in lung cancer ACCP

evidence- based clinical practice guidelines

(2nd edition)

Kvale Chest 2007

Superior vena cava syndrome

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

Radiotherapy

bull Mostly clinical response within 72 h

bull Complete clinical response at 2 w in 78 of patients with SCLC

and 63 of patients with NSCLC

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

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Duhamel Atlas clinique des maladies

des voies aeacuteriennes Elsevier

wwwupmccancercenterscom

Endobronchial brachytherapy

Cochrane analysis (Cardona The Cochrane

Library 2008)

bull No improved

symptom relief by

addition of

endobronchial

brachytherapy to

EBRT

bull Indicated in selected

patients pretreated

by EBRT with

central

endobronchial

obstruction

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Ozkok Lung Cancer 2008

Endobronchial brachytherapy

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Take home lung cancer

Dosefractionation

bull Minimum 10x3 Gy 5xw or equivalent

ndash better symptom control and better overall survival

ndash But more toxicity

bull Short schedule for symptom control and limited toxicity

ndashPoor performance status limited life expectancy

Timing

bull RT at the moment of symptom onset

bull No place for bdquoprophylactic palliative RTldquo according to evidence based guidelines

ndashExceptions

bull Young patient good PS aim of local control

bull Imminent symptoms (superior vena cava syndrome central airway obstruction

Rodrigues Pract Rad Oncol 2011

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

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Homs Eur J CancerLancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

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Randomisierte Studien

Homs Lancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

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Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

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Scoccianti Radiother Oncol 2012

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 100

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SRO Tutorial Palliative Care ndash Palliative Radiotherapy 101

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SRO Tutorial Palliative Care ndash Palliative Radiotherapy 22

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull EBRT significant palliation of painful bone metastasis in

50-80 of patients complete pain relief in up to 13 of

patients (Chow JCO 2007)

bull Optimal fractionation RT technique combination with other

treatment options

bull Systematic review combined with expert opinions

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 23

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Uncomplicated bone

metastasis

Single vs multiple

fractions

bull Pain relief

equivalent

bull Long term toxicity

equivalent

bull Single fraction

optimal patient and

caregiver

convenience

bull Retreatment rate

20 vs 8

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 24

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Repeat treatment of painful spinal metastasis

bull Pain relief in 46-80

bull Cave dose to spinal cord

bull Dosefractionation unclear

bull Recommendation prospective trial

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 25

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Comparable fracture risk Chow Clin Oncol 2012

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 26

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Comparable risk of

spinal cord

compression

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 27

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SBRT of spinal metastasis

bull Mostly retrospective single-institution series

bull Recommendation prospective trial

bull Not primary treatment for spinal met causing spinal cord

compression

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 28

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Radionuclides

bull Important often underused option for multifocal bone

metastasis

bull For osteoblastic metastasis

bull Based on available data do not obviate need for EBRT

bull Recommendation prospective studies on prophylactic use

of radiopharmaceuticals in patients with limited bone

metastases combination with other systemic agents

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 29

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 30

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Biphosphonates

bull Several prospective studies on concurrent EBRT and

biphosphonates successful pain relief promotion of re-

ossification of damaged bone acceptable risk of toxicity

bull Not shown that combination better than EBRT alone for

pain relief

bull Recommendation prospective trial on optimum RT

fractionation EBRT versus radionuclides dose and

duration of biphosphonates and scheduling

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 31

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 32

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Denosumab

Lipton Curr Opp Supp Pall Care 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 33

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lipton Curr Opp Supp

Pall Care 2011

Denosumab versus

Zoledronate

Prevention of SREs (path fracture RT or OP to bone

spinal cord compression)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 34

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Breast

superior

Prostate

superior

Other solid

tumors or

multiple

myeloma

non inferior

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 35

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Vertebroplastykyphoplasty

bull No prospective data to suggest

that vertkyph obviates the

need for EBRT in painful bone

met

bull Small series of patients treated

by vertkyph plus EBRT

bull Recommendation prospective

trials on patient selection

efficacy toxicity and timing of

vertkyph and RT

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 36

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 37

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Non inferiority study

bull 272 patients randomized

Neuropathic pain

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 38

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 39

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 40

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Spinal cord compression

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 41

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 42

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 43

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Patchell Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 44

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

RT short versus

long course

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 45

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 46

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 47

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 48

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 49

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 50

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull SRO tutorial CNS PD Dr A Pica

bull ScocciantiRicardi Radiother Oncol 2012 Review

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 51

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemorrhage

bull Bleeding in 6-10 of patients with advanced

cancer (Pereira et al Topics in Palliative Care Vol 4 New York

Oxford University Press 2000)

bull haemoptysis

bull haematemesis

bull haematocheziamelaena

bull vaginal bleeding

bull haematuria

bull bleeding in ulcerated skin lesions

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 52

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Mechanisms of haemostatic radiotherapy

bull Sparse literature

bull Coagulation activationsup1

ndash Oxydative endothelial damage

ndash Activation of thrombocytes

ndash Activation of inflammation

bull Long term anti-angiogenetic

sup1 Hallahan et al Oncology (Huntingt) 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 53

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Prostate cancer

bull Reduction of pain and bleeding in hormone refractory

prostate cancer (Kynaston Br J Urol 1990 Kawakami Nippon

Hinyokika Gakkai Zasshi 1993 Kalapurakal Int J Radiat Oncol Biol Phys

2003)

bull 100 improvement in patients with important hematuria (Carlton J Urol 1972)

Bladder cancer (Srinivasan et al Clin Oncol (R Coll Radiol) 1994)

bull 17 Gy in 2 fractions3 days 59 clearance of hematuria

bull 45 Gy in 12 fractions26 days 16 clearance of

hematuria

bull Selection by performance status Palliation (pain and

hematuria) better with hypofractionated RT worse

survival

bull No important side effects

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 54

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung cancer

bull Control of hemoptysis in up to 80 of patients (Brundage

Can J Oncol 1996 Medical Research Council Lung Cancer Working Party

Br J Cancer 1992 Hoskin in Doyle et al Second Edition New York

Oxford University Press 1998 Langendijk Int J Radiat Oncol Biol Phys

2000)

bull Optimal dosefractionation

ndash Hypofractionated RT seems to be equally effective to multiple

fractions (Rees Clin Oncol (R Coll Radiol) 1997 Sundstrom JCO

2004 Phase III Stevens Australas Radiol 1995 Phase III studies of

the MRC (s above)

ndash 10 Gy Single fraction equally effective to multiple fractions less

toxic (Hoskin in Doyle et al Second Edition New York Oxford

University Press 1998 Medical Research Council Lung Cancer

Working Party Br J Cancer 1992)

ndash Mostly total dose of around 20 Gy (multiple fractions) or 8 Gy

single fraction recommended

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 55

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Van Lonkhuijzen

Radiother Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 56

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gynaecologic tumours

bull Cf review van Lonkhuijzen Radiother Oncol 2011

bull Consider intracavitary HDR brachytherapy

Rectal cancer

bull Up to 85 control of rectal bleeding (Hoskin in Doyle et al Second Edition New York Oxford University Press 1998)

Kaposi sarcoma

bull Good palliation for pain bleeding or edema TD 15-40 Gy SD 2 Gy gt90 response 70 complete remission (Review Becker et al Onkologie 2006)

Skin tumours (Miller in Doyle Oxford Textbook of Palliative Medicine New York Oxford University Press 1993)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 57

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duration of treatment effect

Lung cancer

bull Median duration of palliation 50 of remaining life span (30 Gy10d

27 Gy6d 17 Gy2 fract1w apart) (Medical Research Council Br J

Cancer 1991)

bull 1 fract 10 Gy vs 2 fract 85 Gy more patients need repeat RT (Medical Research Council Lung Cancer Working Party Br J Cancer 1992)

bull 417 pat need repeat RT within 3 m after 1x10 Gy (Scolaro Radiol

Med 1995)

Rec ovarian cancer

bull Median duration of palliation 4 m in 90 of patients until death (Corn Cancer 1994)

Cervical endometrial cancer

bull In 50 of patients pall Effect until death with 1-2x10 Gy

ndash Halle IJROBP 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 58

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull RT effective for improvement of

ndashThoracic symptoms (haemoptysis cough thoracic pain

dyspnoea airway obstruction) (Sirzeacuten Acta Oncol 2003 and others)

ndashQOL in about 13 of patients (Langendijk IJROBP 2000)

RT schedules

bull Systematic review (Fairchild JCO 264001-4011 2008)

ndash13 randomized trials 3473 patients

ndashdifferent RT schedules

ndashAim find optimal RT schedule for maximal palliation with

minimal toxicityneed for reirradiation

Thoracic symptoms

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 59

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz

Cancer

2007

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz Chow Hartsell Konski Cancer 2007

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemoptysis

bull Fig2 toux

733 689

812 802

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 62

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig3 doul thor 321 279

535 482

Cough

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 63

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 4 overall symptom burden

575 519

648 638

Thoracic pain

Fairchild JCO 2008

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 5 survie 1a

Cutoff (sensitivity analysis) BED[10] 35Gy vs LD

100 162

555 609

Overall symptom burden

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 65

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cutoff BED[10] 35Gy vs LD

265 217

Overall survival at 1y

Fairchild JCO 2008

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 7 Tox dysphagie

Cutoff BED[10] 30Gy vs LD

205 149

about x 2

Toxicity (dysphagia)

Fairchild JCO 2008

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomized trial 250 patients (Falk BMJ 2002)

bull Locally advanced non resectable NSCLC with minimal thoracic symptoms

bull Immediate vs delayed RT (at symptom onset)

bull In delayed arm 56 of patients died without RT

bull No difference in QOL odr OS

bull More acute toxicity in immediate RT arm

Randomized trial (Sundstrom Radiother Oncol 2005)

bull Advanced NSCLC

bull 2 RT schedules (5x4Gy vs 2x85 Gy) immediate RT

bull Stratification according to presenceabsence of thoracic symptoms

bull In asymptomatic patients no long term symptom control but important dysphagia

Timing

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull in 97 malignant

bull in 5-10 of lung cancer patients

bull Histology (exclude benign disease RT-chemosensible tumours

bull Generally spontanous improvement of symptoms by formation of collaterals

Superior vena cava syndrome

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Treatment

1 symptomatic

bull steroids

bull diuretics

bull Elevation of headthorax

2 causal bull chemotherapy (SCLC

lymphomas germinal tumours)

bull Endovascular stent placement

bull radiotherapy Palliative care in lung cancer ACCP

evidence- based clinical practice guidelines

(2nd edition)

Kvale Chest 2007

Superior vena cava syndrome

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

Radiotherapy

bull Mostly clinical response within 72 h

bull Complete clinical response at 2 w in 78 of patients with SCLC

and 63 of patients with NSCLC

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

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Duhamel Atlas clinique des maladies

des voies aeacuteriennes Elsevier

wwwupmccancercenterscom

Endobronchial brachytherapy

Cochrane analysis (Cardona The Cochrane

Library 2008)

bull No improved

symptom relief by

addition of

endobronchial

brachytherapy to

EBRT

bull Indicated in selected

patients pretreated

by EBRT with

central

endobronchial

obstruction

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Ozkok Lung Cancer 2008

Endobronchial brachytherapy

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Take home lung cancer

Dosefractionation

bull Minimum 10x3 Gy 5xw or equivalent

ndash better symptom control and better overall survival

ndash But more toxicity

bull Short schedule for symptom control and limited toxicity

ndashPoor performance status limited life expectancy

Timing

bull RT at the moment of symptom onset

bull No place for bdquoprophylactic palliative RTldquo according to evidence based guidelines

ndashExceptions

bull Young patient good PS aim of local control

bull Imminent symptoms (superior vena cava syndrome central airway obstruction

Rodrigues Pract Rad Oncol 2011

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Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 80

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

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Homs Eur J CancerLancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 98

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

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Scoccianti Radiother Oncol 2012

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SRO Tutorial Palliative Care ndash Palliative Radiotherapy 23

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Uncomplicated bone

metastasis

Single vs multiple

fractions

bull Pain relief

equivalent

bull Long term toxicity

equivalent

bull Single fraction

optimal patient and

caregiver

convenience

bull Retreatment rate

20 vs 8

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 24

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Repeat treatment of painful spinal metastasis

bull Pain relief in 46-80

bull Cave dose to spinal cord

bull Dosefractionation unclear

bull Recommendation prospective trial

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 25

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Comparable fracture risk Chow Clin Oncol 2012

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 26

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Comparable risk of

spinal cord

compression

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 27

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SBRT of spinal metastasis

bull Mostly retrospective single-institution series

bull Recommendation prospective trial

bull Not primary treatment for spinal met causing spinal cord

compression

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 28

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Radionuclides

bull Important often underused option for multifocal bone

metastasis

bull For osteoblastic metastasis

bull Based on available data do not obviate need for EBRT

bull Recommendation prospective studies on prophylactic use

of radiopharmaceuticals in patients with limited bone

metastases combination with other systemic agents

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 29

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 30

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Biphosphonates

bull Several prospective studies on concurrent EBRT and

biphosphonates successful pain relief promotion of re-

ossification of damaged bone acceptable risk of toxicity

bull Not shown that combination better than EBRT alone for

pain relief

bull Recommendation prospective trial on optimum RT

fractionation EBRT versus radionuclides dose and

duration of biphosphonates and scheduling

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 31

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 32

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Denosumab

Lipton Curr Opp Supp Pall Care 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 33

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lipton Curr Opp Supp

Pall Care 2011

Denosumab versus

Zoledronate

Prevention of SREs (path fracture RT or OP to bone

spinal cord compression)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 34

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Breast

superior

Prostate

superior

Other solid

tumors or

multiple

myeloma

non inferior

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 35

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Vertebroplastykyphoplasty

bull No prospective data to suggest

that vertkyph obviates the

need for EBRT in painful bone

met

bull Small series of patients treated

by vertkyph plus EBRT

bull Recommendation prospective

trials on patient selection

efficacy toxicity and timing of

vertkyph and RT

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 36

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 37

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Non inferiority study

bull 272 patients randomized

Neuropathic pain

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 38

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 39

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 40

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Spinal cord compression

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 41

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 42

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 43

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Patchell Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 44

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

RT short versus

long course

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 45

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 46

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 47

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 48

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 49

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 50

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull SRO tutorial CNS PD Dr A Pica

bull ScocciantiRicardi Radiother Oncol 2012 Review

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 51

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemorrhage

bull Bleeding in 6-10 of patients with advanced

cancer (Pereira et al Topics in Palliative Care Vol 4 New York

Oxford University Press 2000)

bull haemoptysis

bull haematemesis

bull haematocheziamelaena

bull vaginal bleeding

bull haematuria

bull bleeding in ulcerated skin lesions

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 52

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Mechanisms of haemostatic radiotherapy

bull Sparse literature

bull Coagulation activationsup1

ndash Oxydative endothelial damage

ndash Activation of thrombocytes

ndash Activation of inflammation

bull Long term anti-angiogenetic

sup1 Hallahan et al Oncology (Huntingt) 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 53

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Prostate cancer

bull Reduction of pain and bleeding in hormone refractory

prostate cancer (Kynaston Br J Urol 1990 Kawakami Nippon

Hinyokika Gakkai Zasshi 1993 Kalapurakal Int J Radiat Oncol Biol Phys

2003)

bull 100 improvement in patients with important hematuria (Carlton J Urol 1972)

Bladder cancer (Srinivasan et al Clin Oncol (R Coll Radiol) 1994)

bull 17 Gy in 2 fractions3 days 59 clearance of hematuria

bull 45 Gy in 12 fractions26 days 16 clearance of

hematuria

bull Selection by performance status Palliation (pain and

hematuria) better with hypofractionated RT worse

survival

bull No important side effects

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 54

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung cancer

bull Control of hemoptysis in up to 80 of patients (Brundage

Can J Oncol 1996 Medical Research Council Lung Cancer Working Party

Br J Cancer 1992 Hoskin in Doyle et al Second Edition New York

Oxford University Press 1998 Langendijk Int J Radiat Oncol Biol Phys

2000)

bull Optimal dosefractionation

ndash Hypofractionated RT seems to be equally effective to multiple

fractions (Rees Clin Oncol (R Coll Radiol) 1997 Sundstrom JCO

2004 Phase III Stevens Australas Radiol 1995 Phase III studies of

the MRC (s above)

ndash 10 Gy Single fraction equally effective to multiple fractions less

toxic (Hoskin in Doyle et al Second Edition New York Oxford

University Press 1998 Medical Research Council Lung Cancer

Working Party Br J Cancer 1992)

ndash Mostly total dose of around 20 Gy (multiple fractions) or 8 Gy

single fraction recommended

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 55

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Van Lonkhuijzen

Radiother Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 56

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Gynaecologic tumours

bull Cf review van Lonkhuijzen Radiother Oncol 2011

bull Consider intracavitary HDR brachytherapy

Rectal cancer

bull Up to 85 control of rectal bleeding (Hoskin in Doyle et al Second Edition New York Oxford University Press 1998)

Kaposi sarcoma

bull Good palliation for pain bleeding or edema TD 15-40 Gy SD 2 Gy gt90 response 70 complete remission (Review Becker et al Onkologie 2006)

Skin tumours (Miller in Doyle Oxford Textbook of Palliative Medicine New York Oxford University Press 1993)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 57

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duration of treatment effect

Lung cancer

bull Median duration of palliation 50 of remaining life span (30 Gy10d

27 Gy6d 17 Gy2 fract1w apart) (Medical Research Council Br J

Cancer 1991)

bull 1 fract 10 Gy vs 2 fract 85 Gy more patients need repeat RT (Medical Research Council Lung Cancer Working Party Br J Cancer 1992)

bull 417 pat need repeat RT within 3 m after 1x10 Gy (Scolaro Radiol

Med 1995)

Rec ovarian cancer

bull Median duration of palliation 4 m in 90 of patients until death (Corn Cancer 1994)

Cervical endometrial cancer

bull In 50 of patients pall Effect until death with 1-2x10 Gy

ndash Halle IJROBP 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 58

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull RT effective for improvement of

ndashThoracic symptoms (haemoptysis cough thoracic pain

dyspnoea airway obstruction) (Sirzeacuten Acta Oncol 2003 and others)

ndashQOL in about 13 of patients (Langendijk IJROBP 2000)

RT schedules

bull Systematic review (Fairchild JCO 264001-4011 2008)

ndash13 randomized trials 3473 patients

ndashdifferent RT schedules

ndashAim find optimal RT schedule for maximal palliation with

minimal toxicityneed for reirradiation

Thoracic symptoms

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz

Cancer

2007

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Lutz Chow Hartsell Konski Cancer 2007

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Haemoptysis

bull Fig2 toux

733 689

812 802

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 62

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig3 doul thor 321 279

535 482

Cough

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 63

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 4 overall symptom burden

575 519

648 638

Thoracic pain

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 64

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 5 survie 1a

Cutoff (sensitivity analysis) BED[10] 35Gy vs LD

100 162

555 609

Overall symptom burden

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 65

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cutoff BED[10] 35Gy vs LD

265 217

Overall survival at 1y

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 66

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 7 Tox dysphagie

Cutoff BED[10] 30Gy vs LD

205 149

about x 2

Toxicity (dysphagia)

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 67

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomized trial 250 patients (Falk BMJ 2002)

bull Locally advanced non resectable NSCLC with minimal thoracic symptoms

bull Immediate vs delayed RT (at symptom onset)

bull In delayed arm 56 of patients died without RT

bull No difference in QOL odr OS

bull More acute toxicity in immediate RT arm

Randomized trial (Sundstrom Radiother Oncol 2005)

bull Advanced NSCLC

bull 2 RT schedules (5x4Gy vs 2x85 Gy) immediate RT

bull Stratification according to presenceabsence of thoracic symptoms

bull In asymptomatic patients no long term symptom control but important dysphagia

Timing

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 68

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull in 97 malignant

bull in 5-10 of lung cancer patients

bull Histology (exclude benign disease RT-chemosensible tumours

bull Generally spontanous improvement of symptoms by formation of collaterals

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 69

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Treatment

1 symptomatic

bull steroids

bull diuretics

bull Elevation of headthorax

2 causal bull chemotherapy (SCLC

lymphomas germinal tumours)

bull Endovascular stent placement

bull radiotherapy Palliative care in lung cancer ACCP

evidence- based clinical practice guidelines

(2nd edition)

Kvale Chest 2007

Superior vena cava syndrome

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

Radiotherapy

bull Mostly clinical response within 72 h

bull Complete clinical response at 2 w in 78 of patients with SCLC

and 63 of patients with NSCLC

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 72

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

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Duhamel Atlas clinique des maladies

des voies aeacuteriennes Elsevier

wwwupmccancercenterscom

Endobronchial brachytherapy

Cochrane analysis (Cardona The Cochrane

Library 2008)

bull No improved

symptom relief by

addition of

endobronchial

brachytherapy to

EBRT

bull Indicated in selected

patients pretreated

by EBRT with

central

endobronchial

obstruction

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 74

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Ozkok Lung Cancer 2008

Endobronchial brachytherapy

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Take home lung cancer

Dosefractionation

bull Minimum 10x3 Gy 5xw or equivalent

ndash better symptom control and better overall survival

ndash But more toxicity

bull Short schedule for symptom control and limited toxicity

ndashPoor performance status limited life expectancy

Timing

bull RT at the moment of symptom onset

bull No place for bdquoprophylactic palliative RTldquo according to evidence based guidelines

ndashExceptions

bull Young patient good PS aim of local control

bull Imminent symptoms (superior vena cava syndrome central airway obstruction

Rodrigues Pract Rad Oncol 2011

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 80

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Homs Eur J CancerLancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 83

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 84

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 98

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

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Scoccianti Radiother Oncol 2012

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SRO Tutorial Palliative Care ndash Palliative Radiotherapy 24

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Repeat treatment of painful spinal metastasis

bull Pain relief in 46-80

bull Cave dose to spinal cord

bull Dosefractionation unclear

bull Recommendation prospective trial

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 25

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Comparable fracture risk Chow Clin Oncol 2012

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 26

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Comparable risk of

spinal cord

compression

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 27

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SBRT of spinal metastasis

bull Mostly retrospective single-institution series

bull Recommendation prospective trial

bull Not primary treatment for spinal met causing spinal cord

compression

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 28

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Radionuclides

bull Important often underused option for multifocal bone

metastasis

bull For osteoblastic metastasis

bull Based on available data do not obviate need for EBRT

bull Recommendation prospective studies on prophylactic use

of radiopharmaceuticals in patients with limited bone

metastases combination with other systemic agents

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 29

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 30

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Biphosphonates

bull Several prospective studies on concurrent EBRT and

biphosphonates successful pain relief promotion of re-

ossification of damaged bone acceptable risk of toxicity

bull Not shown that combination better than EBRT alone for

pain relief

bull Recommendation prospective trial on optimum RT

fractionation EBRT versus radionuclides dose and

duration of biphosphonates and scheduling

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 31

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 32

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Denosumab

Lipton Curr Opp Supp Pall Care 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 33

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lipton Curr Opp Supp

Pall Care 2011

Denosumab versus

Zoledronate

Prevention of SREs (path fracture RT or OP to bone

spinal cord compression)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 34

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Breast

superior

Prostate

superior

Other solid

tumors or

multiple

myeloma

non inferior

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 35

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Vertebroplastykyphoplasty

bull No prospective data to suggest

that vertkyph obviates the

need for EBRT in painful bone

met

bull Small series of patients treated

by vertkyph plus EBRT

bull Recommendation prospective

trials on patient selection

efficacy toxicity and timing of

vertkyph and RT

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 36

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 37

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Non inferiority study

bull 272 patients randomized

Neuropathic pain

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 38

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 39

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 40

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Spinal cord compression

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 41

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 42

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 43

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Patchell Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 44

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

RT short versus

long course

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 45

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 46

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 47

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 48

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 49

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 50

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull SRO tutorial CNS PD Dr A Pica

bull ScocciantiRicardi Radiother Oncol 2012 Review

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 51

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemorrhage

bull Bleeding in 6-10 of patients with advanced

cancer (Pereira et al Topics in Palliative Care Vol 4 New York

Oxford University Press 2000)

bull haemoptysis

bull haematemesis

bull haematocheziamelaena

bull vaginal bleeding

bull haematuria

bull bleeding in ulcerated skin lesions

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 52

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Mechanisms of haemostatic radiotherapy

bull Sparse literature

bull Coagulation activationsup1

ndash Oxydative endothelial damage

ndash Activation of thrombocytes

ndash Activation of inflammation

bull Long term anti-angiogenetic

sup1 Hallahan et al Oncology (Huntingt) 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 53

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Prostate cancer

bull Reduction of pain and bleeding in hormone refractory

prostate cancer (Kynaston Br J Urol 1990 Kawakami Nippon

Hinyokika Gakkai Zasshi 1993 Kalapurakal Int J Radiat Oncol Biol Phys

2003)

bull 100 improvement in patients with important hematuria (Carlton J Urol 1972)

Bladder cancer (Srinivasan et al Clin Oncol (R Coll Radiol) 1994)

bull 17 Gy in 2 fractions3 days 59 clearance of hematuria

bull 45 Gy in 12 fractions26 days 16 clearance of

hematuria

bull Selection by performance status Palliation (pain and

hematuria) better with hypofractionated RT worse

survival

bull No important side effects

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 54

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung cancer

bull Control of hemoptysis in up to 80 of patients (Brundage

Can J Oncol 1996 Medical Research Council Lung Cancer Working Party

Br J Cancer 1992 Hoskin in Doyle et al Second Edition New York

Oxford University Press 1998 Langendijk Int J Radiat Oncol Biol Phys

2000)

bull Optimal dosefractionation

ndash Hypofractionated RT seems to be equally effective to multiple

fractions (Rees Clin Oncol (R Coll Radiol) 1997 Sundstrom JCO

2004 Phase III Stevens Australas Radiol 1995 Phase III studies of

the MRC (s above)

ndash 10 Gy Single fraction equally effective to multiple fractions less

toxic (Hoskin in Doyle et al Second Edition New York Oxford

University Press 1998 Medical Research Council Lung Cancer

Working Party Br J Cancer 1992)

ndash Mostly total dose of around 20 Gy (multiple fractions) or 8 Gy

single fraction recommended

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 55

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Van Lonkhuijzen

Radiother Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 56

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Gynaecologic tumours

bull Cf review van Lonkhuijzen Radiother Oncol 2011

bull Consider intracavitary HDR brachytherapy

Rectal cancer

bull Up to 85 control of rectal bleeding (Hoskin in Doyle et al Second Edition New York Oxford University Press 1998)

Kaposi sarcoma

bull Good palliation for pain bleeding or edema TD 15-40 Gy SD 2 Gy gt90 response 70 complete remission (Review Becker et al Onkologie 2006)

Skin tumours (Miller in Doyle Oxford Textbook of Palliative Medicine New York Oxford University Press 1993)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 57

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duration of treatment effect

Lung cancer

bull Median duration of palliation 50 of remaining life span (30 Gy10d

27 Gy6d 17 Gy2 fract1w apart) (Medical Research Council Br J

Cancer 1991)

bull 1 fract 10 Gy vs 2 fract 85 Gy more patients need repeat RT (Medical Research Council Lung Cancer Working Party Br J Cancer 1992)

bull 417 pat need repeat RT within 3 m after 1x10 Gy (Scolaro Radiol

Med 1995)

Rec ovarian cancer

bull Median duration of palliation 4 m in 90 of patients until death (Corn Cancer 1994)

Cervical endometrial cancer

bull In 50 of patients pall Effect until death with 1-2x10 Gy

ndash Halle IJROBP 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 58

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull RT effective for improvement of

ndashThoracic symptoms (haemoptysis cough thoracic pain

dyspnoea airway obstruction) (Sirzeacuten Acta Oncol 2003 and others)

ndashQOL in about 13 of patients (Langendijk IJROBP 2000)

RT schedules

bull Systematic review (Fairchild JCO 264001-4011 2008)

ndash13 randomized trials 3473 patients

ndashdifferent RT schedules

ndashAim find optimal RT schedule for maximal palliation with

minimal toxicityneed for reirradiation

Thoracic symptoms

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 59

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz

Cancer

2007

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz Chow Hartsell Konski Cancer 2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 61

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Haemoptysis

bull Fig2 toux

733 689

812 802

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 62

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig3 doul thor 321 279

535 482

Cough

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 63

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 4 overall symptom burden

575 519

648 638

Thoracic pain

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 64

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 5 survie 1a

Cutoff (sensitivity analysis) BED[10] 35Gy vs LD

100 162

555 609

Overall symptom burden

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 65

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cutoff BED[10] 35Gy vs LD

265 217

Overall survival at 1y

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 66

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 7 Tox dysphagie

Cutoff BED[10] 30Gy vs LD

205 149

about x 2

Toxicity (dysphagia)

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 67

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomized trial 250 patients (Falk BMJ 2002)

bull Locally advanced non resectable NSCLC with minimal thoracic symptoms

bull Immediate vs delayed RT (at symptom onset)

bull In delayed arm 56 of patients died without RT

bull No difference in QOL odr OS

bull More acute toxicity in immediate RT arm

Randomized trial (Sundstrom Radiother Oncol 2005)

bull Advanced NSCLC

bull 2 RT schedules (5x4Gy vs 2x85 Gy) immediate RT

bull Stratification according to presenceabsence of thoracic symptoms

bull In asymptomatic patients no long term symptom control but important dysphagia

Timing

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 68

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull in 97 malignant

bull in 5-10 of lung cancer patients

bull Histology (exclude benign disease RT-chemosensible tumours

bull Generally spontanous improvement of symptoms by formation of collaterals

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 69

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Treatment

1 symptomatic

bull steroids

bull diuretics

bull Elevation of headthorax

2 causal bull chemotherapy (SCLC

lymphomas germinal tumours)

bull Endovascular stent placement

bull radiotherapy Palliative care in lung cancer ACCP

evidence- based clinical practice guidelines

(2nd edition)

Kvale Chest 2007

Superior vena cava syndrome

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

Radiotherapy

bull Mostly clinical response within 72 h

bull Complete clinical response at 2 w in 78 of patients with SCLC

and 63 of patients with NSCLC

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 73

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Duhamel Atlas clinique des maladies

des voies aeacuteriennes Elsevier

wwwupmccancercenterscom

Endobronchial brachytherapy

Cochrane analysis (Cardona The Cochrane

Library 2008)

bull No improved

symptom relief by

addition of

endobronchial

brachytherapy to

EBRT

bull Indicated in selected

patients pretreated

by EBRT with

central

endobronchial

obstruction

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 74

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Ozkok Lung Cancer 2008

Endobronchial brachytherapy

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Take home lung cancer

Dosefractionation

bull Minimum 10x3 Gy 5xw or equivalent

ndash better symptom control and better overall survival

ndash But more toxicity

bull Short schedule for symptom control and limited toxicity

ndashPoor performance status limited life expectancy

Timing

bull RT at the moment of symptom onset

bull No place for bdquoprophylactic palliative RTldquo according to evidence based guidelines

ndashExceptions

bull Young patient good PS aim of local control

bull Imminent symptoms (superior vena cava syndrome central airway obstruction

Rodrigues Pract Rad Oncol 2011

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 80

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 82

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 83

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 84

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 90

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 98

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

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Scoccianti Radiother Oncol 2012

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SRO Tutorial Palliative Care ndash Palliative Radiotherapy 25

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Comparable fracture risk Chow Clin Oncol 2012

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 26

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Comparable risk of

spinal cord

compression

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 27

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SBRT of spinal metastasis

bull Mostly retrospective single-institution series

bull Recommendation prospective trial

bull Not primary treatment for spinal met causing spinal cord

compression

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 28

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Radionuclides

bull Important often underused option for multifocal bone

metastasis

bull For osteoblastic metastasis

bull Based on available data do not obviate need for EBRT

bull Recommendation prospective studies on prophylactic use

of radiopharmaceuticals in patients with limited bone

metastases combination with other systemic agents

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 29

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 30

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Biphosphonates

bull Several prospective studies on concurrent EBRT and

biphosphonates successful pain relief promotion of re-

ossification of damaged bone acceptable risk of toxicity

bull Not shown that combination better than EBRT alone for

pain relief

bull Recommendation prospective trial on optimum RT

fractionation EBRT versus radionuclides dose and

duration of biphosphonates and scheduling

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 31

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 32

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Denosumab

Lipton Curr Opp Supp Pall Care 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 33

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lipton Curr Opp Supp

Pall Care 2011

Denosumab versus

Zoledronate

Prevention of SREs (path fracture RT or OP to bone

spinal cord compression)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 34

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Breast

superior

Prostate

superior

Other solid

tumors or

multiple

myeloma

non inferior

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 35

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Vertebroplastykyphoplasty

bull No prospective data to suggest

that vertkyph obviates the

need for EBRT in painful bone

met

bull Small series of patients treated

by vertkyph plus EBRT

bull Recommendation prospective

trials on patient selection

efficacy toxicity and timing of

vertkyph and RT

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 36

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 37

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Non inferiority study

bull 272 patients randomized

Neuropathic pain

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 38

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 39

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 40

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Spinal cord compression

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 41

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 42

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 43

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Patchell Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 44

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

RT short versus

long course

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 45

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 46

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 47

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 48

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 49

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 50

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull SRO tutorial CNS PD Dr A Pica

bull ScocciantiRicardi Radiother Oncol 2012 Review

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 51

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemorrhage

bull Bleeding in 6-10 of patients with advanced

cancer (Pereira et al Topics in Palliative Care Vol 4 New York

Oxford University Press 2000)

bull haemoptysis

bull haematemesis

bull haematocheziamelaena

bull vaginal bleeding

bull haematuria

bull bleeding in ulcerated skin lesions

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 52

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Mechanisms of haemostatic radiotherapy

bull Sparse literature

bull Coagulation activationsup1

ndash Oxydative endothelial damage

ndash Activation of thrombocytes

ndash Activation of inflammation

bull Long term anti-angiogenetic

sup1 Hallahan et al Oncology (Huntingt) 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 53

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Prostate cancer

bull Reduction of pain and bleeding in hormone refractory

prostate cancer (Kynaston Br J Urol 1990 Kawakami Nippon

Hinyokika Gakkai Zasshi 1993 Kalapurakal Int J Radiat Oncol Biol Phys

2003)

bull 100 improvement in patients with important hematuria (Carlton J Urol 1972)

Bladder cancer (Srinivasan et al Clin Oncol (R Coll Radiol) 1994)

bull 17 Gy in 2 fractions3 days 59 clearance of hematuria

bull 45 Gy in 12 fractions26 days 16 clearance of

hematuria

bull Selection by performance status Palliation (pain and

hematuria) better with hypofractionated RT worse

survival

bull No important side effects

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 54

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung cancer

bull Control of hemoptysis in up to 80 of patients (Brundage

Can J Oncol 1996 Medical Research Council Lung Cancer Working Party

Br J Cancer 1992 Hoskin in Doyle et al Second Edition New York

Oxford University Press 1998 Langendijk Int J Radiat Oncol Biol Phys

2000)

bull Optimal dosefractionation

ndash Hypofractionated RT seems to be equally effective to multiple

fractions (Rees Clin Oncol (R Coll Radiol) 1997 Sundstrom JCO

2004 Phase III Stevens Australas Radiol 1995 Phase III studies of

the MRC (s above)

ndash 10 Gy Single fraction equally effective to multiple fractions less

toxic (Hoskin in Doyle et al Second Edition New York Oxford

University Press 1998 Medical Research Council Lung Cancer

Working Party Br J Cancer 1992)

ndash Mostly total dose of around 20 Gy (multiple fractions) or 8 Gy

single fraction recommended

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 55

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Van Lonkhuijzen

Radiother Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 56

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gynaecologic tumours

bull Cf review van Lonkhuijzen Radiother Oncol 2011

bull Consider intracavitary HDR brachytherapy

Rectal cancer

bull Up to 85 control of rectal bleeding (Hoskin in Doyle et al Second Edition New York Oxford University Press 1998)

Kaposi sarcoma

bull Good palliation for pain bleeding or edema TD 15-40 Gy SD 2 Gy gt90 response 70 complete remission (Review Becker et al Onkologie 2006)

Skin tumours (Miller in Doyle Oxford Textbook of Palliative Medicine New York Oxford University Press 1993)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 57

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duration of treatment effect

Lung cancer

bull Median duration of palliation 50 of remaining life span (30 Gy10d

27 Gy6d 17 Gy2 fract1w apart) (Medical Research Council Br J

Cancer 1991)

bull 1 fract 10 Gy vs 2 fract 85 Gy more patients need repeat RT (Medical Research Council Lung Cancer Working Party Br J Cancer 1992)

bull 417 pat need repeat RT within 3 m after 1x10 Gy (Scolaro Radiol

Med 1995)

Rec ovarian cancer

bull Median duration of palliation 4 m in 90 of patients until death (Corn Cancer 1994)

Cervical endometrial cancer

bull In 50 of patients pall Effect until death with 1-2x10 Gy

ndash Halle IJROBP 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 58

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull RT effective for improvement of

ndashThoracic symptoms (haemoptysis cough thoracic pain

dyspnoea airway obstruction) (Sirzeacuten Acta Oncol 2003 and others)

ndashQOL in about 13 of patients (Langendijk IJROBP 2000)

RT schedules

bull Systematic review (Fairchild JCO 264001-4011 2008)

ndash13 randomized trials 3473 patients

ndashdifferent RT schedules

ndashAim find optimal RT schedule for maximal palliation with

minimal toxicityneed for reirradiation

Thoracic symptoms

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 59

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz

Cancer

2007

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz Chow Hartsell Konski Cancer 2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 61

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemoptysis

bull Fig2 toux

733 689

812 802

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 62

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig3 doul thor 321 279

535 482

Cough

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 63

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 4 overall symptom burden

575 519

648 638

Thoracic pain

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 64

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 5 survie 1a

Cutoff (sensitivity analysis) BED[10] 35Gy vs LD

100 162

555 609

Overall symptom burden

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 65

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cutoff BED[10] 35Gy vs LD

265 217

Overall survival at 1y

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 66

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 7 Tox dysphagie

Cutoff BED[10] 30Gy vs LD

205 149

about x 2

Toxicity (dysphagia)

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 67

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomized trial 250 patients (Falk BMJ 2002)

bull Locally advanced non resectable NSCLC with minimal thoracic symptoms

bull Immediate vs delayed RT (at symptom onset)

bull In delayed arm 56 of patients died without RT

bull No difference in QOL odr OS

bull More acute toxicity in immediate RT arm

Randomized trial (Sundstrom Radiother Oncol 2005)

bull Advanced NSCLC

bull 2 RT schedules (5x4Gy vs 2x85 Gy) immediate RT

bull Stratification according to presenceabsence of thoracic symptoms

bull In asymptomatic patients no long term symptom control but important dysphagia

Timing

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 68

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull in 97 malignant

bull in 5-10 of lung cancer patients

bull Histology (exclude benign disease RT-chemosensible tumours

bull Generally spontanous improvement of symptoms by formation of collaterals

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 69

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Treatment

1 symptomatic

bull steroids

bull diuretics

bull Elevation of headthorax

2 causal bull chemotherapy (SCLC

lymphomas germinal tumours)

bull Endovascular stent placement

bull radiotherapy Palliative care in lung cancer ACCP

evidence- based clinical practice guidelines

(2nd edition)

Kvale Chest 2007

Superior vena cava syndrome

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

Radiotherapy

bull Mostly clinical response within 72 h

bull Complete clinical response at 2 w in 78 of patients with SCLC

and 63 of patients with NSCLC

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 72

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 73

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duhamel Atlas clinique des maladies

des voies aeacuteriennes Elsevier

wwwupmccancercenterscom

Endobronchial brachytherapy

Cochrane analysis (Cardona The Cochrane

Library 2008)

bull No improved

symptom relief by

addition of

endobronchial

brachytherapy to

EBRT

bull Indicated in selected

patients pretreated

by EBRT with

central

endobronchial

obstruction

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 74

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Ozkok Lung Cancer 2008

Endobronchial brachytherapy

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Take home lung cancer

Dosefractionation

bull Minimum 10x3 Gy 5xw or equivalent

ndash better symptom control and better overall survival

ndash But more toxicity

bull Short schedule for symptom control and limited toxicity

ndashPoor performance status limited life expectancy

Timing

bull RT at the moment of symptom onset

bull No place for bdquoprophylactic palliative RTldquo according to evidence based guidelines

ndashExceptions

bull Young patient good PS aim of local control

bull Imminent symptoms (superior vena cava syndrome central airway obstruction

Rodrigues Pract Rad Oncol 2011

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 80

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 82

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 83

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 84

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 85

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 90

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

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Scoccianti Radiother Oncol 2012

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Chow Clin Oncol 2012

Comparable risk of

spinal cord

compression

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 27

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SBRT of spinal metastasis

bull Mostly retrospective single-institution series

bull Recommendation prospective trial

bull Not primary treatment for spinal met causing spinal cord

compression

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 28

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Radionuclides

bull Important often underused option for multifocal bone

metastasis

bull For osteoblastic metastasis

bull Based on available data do not obviate need for EBRT

bull Recommendation prospective studies on prophylactic use

of radiopharmaceuticals in patients with limited bone

metastases combination with other systemic agents

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 29

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 30

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Biphosphonates

bull Several prospective studies on concurrent EBRT and

biphosphonates successful pain relief promotion of re-

ossification of damaged bone acceptable risk of toxicity

bull Not shown that combination better than EBRT alone for

pain relief

bull Recommendation prospective trial on optimum RT

fractionation EBRT versus radionuclides dose and

duration of biphosphonates and scheduling

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 31

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 32

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Denosumab

Lipton Curr Opp Supp Pall Care 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 33

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lipton Curr Opp Supp

Pall Care 2011

Denosumab versus

Zoledronate

Prevention of SREs (path fracture RT or OP to bone

spinal cord compression)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 34

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Breast

superior

Prostate

superior

Other solid

tumors or

multiple

myeloma

non inferior

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 35

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Vertebroplastykyphoplasty

bull No prospective data to suggest

that vertkyph obviates the

need for EBRT in painful bone

met

bull Small series of patients treated

by vertkyph plus EBRT

bull Recommendation prospective

trials on patient selection

efficacy toxicity and timing of

vertkyph and RT

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 36

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 37

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Non inferiority study

bull 272 patients randomized

Neuropathic pain

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 38

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 39

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 40

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Spinal cord compression

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 41

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 42

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 43

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Patchell Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 44

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

RT short versus

long course

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 45

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 46

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 47

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 48

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 49

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 50

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull SRO tutorial CNS PD Dr A Pica

bull ScocciantiRicardi Radiother Oncol 2012 Review

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 51

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemorrhage

bull Bleeding in 6-10 of patients with advanced

cancer (Pereira et al Topics in Palliative Care Vol 4 New York

Oxford University Press 2000)

bull haemoptysis

bull haematemesis

bull haematocheziamelaena

bull vaginal bleeding

bull haematuria

bull bleeding in ulcerated skin lesions

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 52

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Mechanisms of haemostatic radiotherapy

bull Sparse literature

bull Coagulation activationsup1

ndash Oxydative endothelial damage

ndash Activation of thrombocytes

ndash Activation of inflammation

bull Long term anti-angiogenetic

sup1 Hallahan et al Oncology (Huntingt) 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 53

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Prostate cancer

bull Reduction of pain and bleeding in hormone refractory

prostate cancer (Kynaston Br J Urol 1990 Kawakami Nippon

Hinyokika Gakkai Zasshi 1993 Kalapurakal Int J Radiat Oncol Biol Phys

2003)

bull 100 improvement in patients with important hematuria (Carlton J Urol 1972)

Bladder cancer (Srinivasan et al Clin Oncol (R Coll Radiol) 1994)

bull 17 Gy in 2 fractions3 days 59 clearance of hematuria

bull 45 Gy in 12 fractions26 days 16 clearance of

hematuria

bull Selection by performance status Palliation (pain and

hematuria) better with hypofractionated RT worse

survival

bull No important side effects

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 54

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung cancer

bull Control of hemoptysis in up to 80 of patients (Brundage

Can J Oncol 1996 Medical Research Council Lung Cancer Working Party

Br J Cancer 1992 Hoskin in Doyle et al Second Edition New York

Oxford University Press 1998 Langendijk Int J Radiat Oncol Biol Phys

2000)

bull Optimal dosefractionation

ndash Hypofractionated RT seems to be equally effective to multiple

fractions (Rees Clin Oncol (R Coll Radiol) 1997 Sundstrom JCO

2004 Phase III Stevens Australas Radiol 1995 Phase III studies of

the MRC (s above)

ndash 10 Gy Single fraction equally effective to multiple fractions less

toxic (Hoskin in Doyle et al Second Edition New York Oxford

University Press 1998 Medical Research Council Lung Cancer

Working Party Br J Cancer 1992)

ndash Mostly total dose of around 20 Gy (multiple fractions) or 8 Gy

single fraction recommended

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 55

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Van Lonkhuijzen

Radiother Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 56

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Gynaecologic tumours

bull Cf review van Lonkhuijzen Radiother Oncol 2011

bull Consider intracavitary HDR brachytherapy

Rectal cancer

bull Up to 85 control of rectal bleeding (Hoskin in Doyle et al Second Edition New York Oxford University Press 1998)

Kaposi sarcoma

bull Good palliation for pain bleeding or edema TD 15-40 Gy SD 2 Gy gt90 response 70 complete remission (Review Becker et al Onkologie 2006)

Skin tumours (Miller in Doyle Oxford Textbook of Palliative Medicine New York Oxford University Press 1993)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 57

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duration of treatment effect

Lung cancer

bull Median duration of palliation 50 of remaining life span (30 Gy10d

27 Gy6d 17 Gy2 fract1w apart) (Medical Research Council Br J

Cancer 1991)

bull 1 fract 10 Gy vs 2 fract 85 Gy more patients need repeat RT (Medical Research Council Lung Cancer Working Party Br J Cancer 1992)

bull 417 pat need repeat RT within 3 m after 1x10 Gy (Scolaro Radiol

Med 1995)

Rec ovarian cancer

bull Median duration of palliation 4 m in 90 of patients until death (Corn Cancer 1994)

Cervical endometrial cancer

bull In 50 of patients pall Effect until death with 1-2x10 Gy

ndash Halle IJROBP 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 58

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull RT effective for improvement of

ndashThoracic symptoms (haemoptysis cough thoracic pain

dyspnoea airway obstruction) (Sirzeacuten Acta Oncol 2003 and others)

ndashQOL in about 13 of patients (Langendijk IJROBP 2000)

RT schedules

bull Systematic review (Fairchild JCO 264001-4011 2008)

ndash13 randomized trials 3473 patients

ndashdifferent RT schedules

ndashAim find optimal RT schedule for maximal palliation with

minimal toxicityneed for reirradiation

Thoracic symptoms

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 59

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz

Cancer

2007

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Lutz Chow Hartsell Konski Cancer 2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 61

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Haemoptysis

bull Fig2 toux

733 689

812 802

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 62

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig3 doul thor 321 279

535 482

Cough

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 63

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 4 overall symptom burden

575 519

648 638

Thoracic pain

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 64

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 5 survie 1a

Cutoff (sensitivity analysis) BED[10] 35Gy vs LD

100 162

555 609

Overall symptom burden

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 65

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cutoff BED[10] 35Gy vs LD

265 217

Overall survival at 1y

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 66

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 7 Tox dysphagie

Cutoff BED[10] 30Gy vs LD

205 149

about x 2

Toxicity (dysphagia)

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 67

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomized trial 250 patients (Falk BMJ 2002)

bull Locally advanced non resectable NSCLC with minimal thoracic symptoms

bull Immediate vs delayed RT (at symptom onset)

bull In delayed arm 56 of patients died without RT

bull No difference in QOL odr OS

bull More acute toxicity in immediate RT arm

Randomized trial (Sundstrom Radiother Oncol 2005)

bull Advanced NSCLC

bull 2 RT schedules (5x4Gy vs 2x85 Gy) immediate RT

bull Stratification according to presenceabsence of thoracic symptoms

bull In asymptomatic patients no long term symptom control but important dysphagia

Timing

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 68

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull in 97 malignant

bull in 5-10 of lung cancer patients

bull Histology (exclude benign disease RT-chemosensible tumours

bull Generally spontanous improvement of symptoms by formation of collaterals

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 69

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Treatment

1 symptomatic

bull steroids

bull diuretics

bull Elevation of headthorax

2 causal bull chemotherapy (SCLC

lymphomas germinal tumours)

bull Endovascular stent placement

bull radiotherapy Palliative care in lung cancer ACCP

evidence- based clinical practice guidelines

(2nd edition)

Kvale Chest 2007

Superior vena cava syndrome

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

Radiotherapy

bull Mostly clinical response within 72 h

bull Complete clinical response at 2 w in 78 of patients with SCLC

and 63 of patients with NSCLC

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 72

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

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Duhamel Atlas clinique des maladies

des voies aeacuteriennes Elsevier

wwwupmccancercenterscom

Endobronchial brachytherapy

Cochrane analysis (Cardona The Cochrane

Library 2008)

bull No improved

symptom relief by

addition of

endobronchial

brachytherapy to

EBRT

bull Indicated in selected

patients pretreated

by EBRT with

central

endobronchial

obstruction

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 74

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Ozkok Lung Cancer 2008

Endobronchial brachytherapy

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Take home lung cancer

Dosefractionation

bull Minimum 10x3 Gy 5xw or equivalent

ndash better symptom control and better overall survival

ndash But more toxicity

bull Short schedule for symptom control and limited toxicity

ndashPoor performance status limited life expectancy

Timing

bull RT at the moment of symptom onset

bull No place for bdquoprophylactic palliative RTldquo according to evidence based guidelines

ndashExceptions

bull Young patient good PS aim of local control

bull Imminent symptoms (superior vena cava syndrome central airway obstruction

Rodrigues Pract Rad Oncol 2011

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 80

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 82

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 83

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 84

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 90

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

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Scoccianti Radiother Oncol 2012

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SRO Tutorial Palliative Care ndash Palliative Radiotherapy 27

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SBRT of spinal metastasis

bull Mostly retrospective single-institution series

bull Recommendation prospective trial

bull Not primary treatment for spinal met causing spinal cord

compression

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 28

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Radionuclides

bull Important often underused option for multifocal bone

metastasis

bull For osteoblastic metastasis

bull Based on available data do not obviate need for EBRT

bull Recommendation prospective studies on prophylactic use

of radiopharmaceuticals in patients with limited bone

metastases combination with other systemic agents

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 29

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 30

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Biphosphonates

bull Several prospective studies on concurrent EBRT and

biphosphonates successful pain relief promotion of re-

ossification of damaged bone acceptable risk of toxicity

bull Not shown that combination better than EBRT alone for

pain relief

bull Recommendation prospective trial on optimum RT

fractionation EBRT versus radionuclides dose and

duration of biphosphonates and scheduling

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 31

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 32

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Denosumab

Lipton Curr Opp Supp Pall Care 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 33

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lipton Curr Opp Supp

Pall Care 2011

Denosumab versus

Zoledronate

Prevention of SREs (path fracture RT or OP to bone

spinal cord compression)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 34

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Breast

superior

Prostate

superior

Other solid

tumors or

multiple

myeloma

non inferior

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 35

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Vertebroplastykyphoplasty

bull No prospective data to suggest

that vertkyph obviates the

need for EBRT in painful bone

met

bull Small series of patients treated

by vertkyph plus EBRT

bull Recommendation prospective

trials on patient selection

efficacy toxicity and timing of

vertkyph and RT

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 36

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 37

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Non inferiority study

bull 272 patients randomized

Neuropathic pain

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 38

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 39

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 40

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Spinal cord compression

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 41

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 42

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 43

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Patchell Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 44

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

RT short versus

long course

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 45

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 46

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 47

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 48

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 49

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 50

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull SRO tutorial CNS PD Dr A Pica

bull ScocciantiRicardi Radiother Oncol 2012 Review

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 51

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemorrhage

bull Bleeding in 6-10 of patients with advanced

cancer (Pereira et al Topics in Palliative Care Vol 4 New York

Oxford University Press 2000)

bull haemoptysis

bull haematemesis

bull haematocheziamelaena

bull vaginal bleeding

bull haematuria

bull bleeding in ulcerated skin lesions

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 52

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Mechanisms of haemostatic radiotherapy

bull Sparse literature

bull Coagulation activationsup1

ndash Oxydative endothelial damage

ndash Activation of thrombocytes

ndash Activation of inflammation

bull Long term anti-angiogenetic

sup1 Hallahan et al Oncology (Huntingt) 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 53

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Prostate cancer

bull Reduction of pain and bleeding in hormone refractory

prostate cancer (Kynaston Br J Urol 1990 Kawakami Nippon

Hinyokika Gakkai Zasshi 1993 Kalapurakal Int J Radiat Oncol Biol Phys

2003)

bull 100 improvement in patients with important hematuria (Carlton J Urol 1972)

Bladder cancer (Srinivasan et al Clin Oncol (R Coll Radiol) 1994)

bull 17 Gy in 2 fractions3 days 59 clearance of hematuria

bull 45 Gy in 12 fractions26 days 16 clearance of

hematuria

bull Selection by performance status Palliation (pain and

hematuria) better with hypofractionated RT worse

survival

bull No important side effects

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 54

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung cancer

bull Control of hemoptysis in up to 80 of patients (Brundage

Can J Oncol 1996 Medical Research Council Lung Cancer Working Party

Br J Cancer 1992 Hoskin in Doyle et al Second Edition New York

Oxford University Press 1998 Langendijk Int J Radiat Oncol Biol Phys

2000)

bull Optimal dosefractionation

ndash Hypofractionated RT seems to be equally effective to multiple

fractions (Rees Clin Oncol (R Coll Radiol) 1997 Sundstrom JCO

2004 Phase III Stevens Australas Radiol 1995 Phase III studies of

the MRC (s above)

ndash 10 Gy Single fraction equally effective to multiple fractions less

toxic (Hoskin in Doyle et al Second Edition New York Oxford

University Press 1998 Medical Research Council Lung Cancer

Working Party Br J Cancer 1992)

ndash Mostly total dose of around 20 Gy (multiple fractions) or 8 Gy

single fraction recommended

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 55

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Van Lonkhuijzen

Radiother Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 56

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gynaecologic tumours

bull Cf review van Lonkhuijzen Radiother Oncol 2011

bull Consider intracavitary HDR brachytherapy

Rectal cancer

bull Up to 85 control of rectal bleeding (Hoskin in Doyle et al Second Edition New York Oxford University Press 1998)

Kaposi sarcoma

bull Good palliation for pain bleeding or edema TD 15-40 Gy SD 2 Gy gt90 response 70 complete remission (Review Becker et al Onkologie 2006)

Skin tumours (Miller in Doyle Oxford Textbook of Palliative Medicine New York Oxford University Press 1993)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 57

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duration of treatment effect

Lung cancer

bull Median duration of palliation 50 of remaining life span (30 Gy10d

27 Gy6d 17 Gy2 fract1w apart) (Medical Research Council Br J

Cancer 1991)

bull 1 fract 10 Gy vs 2 fract 85 Gy more patients need repeat RT (Medical Research Council Lung Cancer Working Party Br J Cancer 1992)

bull 417 pat need repeat RT within 3 m after 1x10 Gy (Scolaro Radiol

Med 1995)

Rec ovarian cancer

bull Median duration of palliation 4 m in 90 of patients until death (Corn Cancer 1994)

Cervical endometrial cancer

bull In 50 of patients pall Effect until death with 1-2x10 Gy

ndash Halle IJROBP 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 58

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull RT effective for improvement of

ndashThoracic symptoms (haemoptysis cough thoracic pain

dyspnoea airway obstruction) (Sirzeacuten Acta Oncol 2003 and others)

ndashQOL in about 13 of patients (Langendijk IJROBP 2000)

RT schedules

bull Systematic review (Fairchild JCO 264001-4011 2008)

ndash13 randomized trials 3473 patients

ndashdifferent RT schedules

ndashAim find optimal RT schedule for maximal palliation with

minimal toxicityneed for reirradiation

Thoracic symptoms

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 59

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz

Cancer

2007

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz Chow Hartsell Konski Cancer 2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 61

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemoptysis

bull Fig2 toux

733 689

812 802

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 62

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig3 doul thor 321 279

535 482

Cough

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 63

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 4 overall symptom burden

575 519

648 638

Thoracic pain

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 64

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 5 survie 1a

Cutoff (sensitivity analysis) BED[10] 35Gy vs LD

100 162

555 609

Overall symptom burden

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 65

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cutoff BED[10] 35Gy vs LD

265 217

Overall survival at 1y

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 66

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 7 Tox dysphagie

Cutoff BED[10] 30Gy vs LD

205 149

about x 2

Toxicity (dysphagia)

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 67

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomized trial 250 patients (Falk BMJ 2002)

bull Locally advanced non resectable NSCLC with minimal thoracic symptoms

bull Immediate vs delayed RT (at symptom onset)

bull In delayed arm 56 of patients died without RT

bull No difference in QOL odr OS

bull More acute toxicity in immediate RT arm

Randomized trial (Sundstrom Radiother Oncol 2005)

bull Advanced NSCLC

bull 2 RT schedules (5x4Gy vs 2x85 Gy) immediate RT

bull Stratification according to presenceabsence of thoracic symptoms

bull In asymptomatic patients no long term symptom control but important dysphagia

Timing

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 68

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull in 97 malignant

bull in 5-10 of lung cancer patients

bull Histology (exclude benign disease RT-chemosensible tumours

bull Generally spontanous improvement of symptoms by formation of collaterals

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 69

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Treatment

1 symptomatic

bull steroids

bull diuretics

bull Elevation of headthorax

2 causal bull chemotherapy (SCLC

lymphomas germinal tumours)

bull Endovascular stent placement

bull radiotherapy Palliative care in lung cancer ACCP

evidence- based clinical practice guidelines

(2nd edition)

Kvale Chest 2007

Superior vena cava syndrome

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

Radiotherapy

bull Mostly clinical response within 72 h

bull Complete clinical response at 2 w in 78 of patients with SCLC

and 63 of patients with NSCLC

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 73

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duhamel Atlas clinique des maladies

des voies aeacuteriennes Elsevier

wwwupmccancercenterscom

Endobronchial brachytherapy

Cochrane analysis (Cardona The Cochrane

Library 2008)

bull No improved

symptom relief by

addition of

endobronchial

brachytherapy to

EBRT

bull Indicated in selected

patients pretreated

by EBRT with

central

endobronchial

obstruction

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 74

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Ozkok Lung Cancer 2008

Endobronchial brachytherapy

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Take home lung cancer

Dosefractionation

bull Minimum 10x3 Gy 5xw or equivalent

ndash better symptom control and better overall survival

ndash But more toxicity

bull Short schedule for symptom control and limited toxicity

ndashPoor performance status limited life expectancy

Timing

bull RT at the moment of symptom onset

bull No place for bdquoprophylactic palliative RTldquo according to evidence based guidelines

ndashExceptions

bull Young patient good PS aim of local control

bull Imminent symptoms (superior vena cava syndrome central airway obstruction

Rodrigues Pract Rad Oncol 2011

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 80

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Homs Eur J CancerLancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 83

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 84

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 85

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 90

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

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Scoccianti Radiother Oncol 2012

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SRO Tutorial Palliative Care ndash Palliative Radiotherapy 28

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Radionuclides

bull Important often underused option for multifocal bone

metastasis

bull For osteoblastic metastasis

bull Based on available data do not obviate need for EBRT

bull Recommendation prospective studies on prophylactic use

of radiopharmaceuticals in patients with limited bone

metastases combination with other systemic agents

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 29

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 30

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Biphosphonates

bull Several prospective studies on concurrent EBRT and

biphosphonates successful pain relief promotion of re-

ossification of damaged bone acceptable risk of toxicity

bull Not shown that combination better than EBRT alone for

pain relief

bull Recommendation prospective trial on optimum RT

fractionation EBRT versus radionuclides dose and

duration of biphosphonates and scheduling

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 31

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 32

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Denosumab

Lipton Curr Opp Supp Pall Care 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 33

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lipton Curr Opp Supp

Pall Care 2011

Denosumab versus

Zoledronate

Prevention of SREs (path fracture RT or OP to bone

spinal cord compression)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 34

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Breast

superior

Prostate

superior

Other solid

tumors or

multiple

myeloma

non inferior

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 35

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Vertebroplastykyphoplasty

bull No prospective data to suggest

that vertkyph obviates the

need for EBRT in painful bone

met

bull Small series of patients treated

by vertkyph plus EBRT

bull Recommendation prospective

trials on patient selection

efficacy toxicity and timing of

vertkyph and RT

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 36

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 37

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Non inferiority study

bull 272 patients randomized

Neuropathic pain

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 38

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 39

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 40

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Spinal cord compression

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 41

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 42

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 43

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Patchell Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 44

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

RT short versus

long course

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 45

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 46

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 47

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 48

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 49

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 50

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull SRO tutorial CNS PD Dr A Pica

bull ScocciantiRicardi Radiother Oncol 2012 Review

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 51

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemorrhage

bull Bleeding in 6-10 of patients with advanced

cancer (Pereira et al Topics in Palliative Care Vol 4 New York

Oxford University Press 2000)

bull haemoptysis

bull haematemesis

bull haematocheziamelaena

bull vaginal bleeding

bull haematuria

bull bleeding in ulcerated skin lesions

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 52

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Mechanisms of haemostatic radiotherapy

bull Sparse literature

bull Coagulation activationsup1

ndash Oxydative endothelial damage

ndash Activation of thrombocytes

ndash Activation of inflammation

bull Long term anti-angiogenetic

sup1 Hallahan et al Oncology (Huntingt) 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 53

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Prostate cancer

bull Reduction of pain and bleeding in hormone refractory

prostate cancer (Kynaston Br J Urol 1990 Kawakami Nippon

Hinyokika Gakkai Zasshi 1993 Kalapurakal Int J Radiat Oncol Biol Phys

2003)

bull 100 improvement in patients with important hematuria (Carlton J Urol 1972)

Bladder cancer (Srinivasan et al Clin Oncol (R Coll Radiol) 1994)

bull 17 Gy in 2 fractions3 days 59 clearance of hematuria

bull 45 Gy in 12 fractions26 days 16 clearance of

hematuria

bull Selection by performance status Palliation (pain and

hematuria) better with hypofractionated RT worse

survival

bull No important side effects

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 54

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung cancer

bull Control of hemoptysis in up to 80 of patients (Brundage

Can J Oncol 1996 Medical Research Council Lung Cancer Working Party

Br J Cancer 1992 Hoskin in Doyle et al Second Edition New York

Oxford University Press 1998 Langendijk Int J Radiat Oncol Biol Phys

2000)

bull Optimal dosefractionation

ndash Hypofractionated RT seems to be equally effective to multiple

fractions (Rees Clin Oncol (R Coll Radiol) 1997 Sundstrom JCO

2004 Phase III Stevens Australas Radiol 1995 Phase III studies of

the MRC (s above)

ndash 10 Gy Single fraction equally effective to multiple fractions less

toxic (Hoskin in Doyle et al Second Edition New York Oxford

University Press 1998 Medical Research Council Lung Cancer

Working Party Br J Cancer 1992)

ndash Mostly total dose of around 20 Gy (multiple fractions) or 8 Gy

single fraction recommended

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 55

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Van Lonkhuijzen

Radiother Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 56

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gynaecologic tumours

bull Cf review van Lonkhuijzen Radiother Oncol 2011

bull Consider intracavitary HDR brachytherapy

Rectal cancer

bull Up to 85 control of rectal bleeding (Hoskin in Doyle et al Second Edition New York Oxford University Press 1998)

Kaposi sarcoma

bull Good palliation for pain bleeding or edema TD 15-40 Gy SD 2 Gy gt90 response 70 complete remission (Review Becker et al Onkologie 2006)

Skin tumours (Miller in Doyle Oxford Textbook of Palliative Medicine New York Oxford University Press 1993)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 57

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duration of treatment effect

Lung cancer

bull Median duration of palliation 50 of remaining life span (30 Gy10d

27 Gy6d 17 Gy2 fract1w apart) (Medical Research Council Br J

Cancer 1991)

bull 1 fract 10 Gy vs 2 fract 85 Gy more patients need repeat RT (Medical Research Council Lung Cancer Working Party Br J Cancer 1992)

bull 417 pat need repeat RT within 3 m after 1x10 Gy (Scolaro Radiol

Med 1995)

Rec ovarian cancer

bull Median duration of palliation 4 m in 90 of patients until death (Corn Cancer 1994)

Cervical endometrial cancer

bull In 50 of patients pall Effect until death with 1-2x10 Gy

ndash Halle IJROBP 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 58

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull RT effective for improvement of

ndashThoracic symptoms (haemoptysis cough thoracic pain

dyspnoea airway obstruction) (Sirzeacuten Acta Oncol 2003 and others)

ndashQOL in about 13 of patients (Langendijk IJROBP 2000)

RT schedules

bull Systematic review (Fairchild JCO 264001-4011 2008)

ndash13 randomized trials 3473 patients

ndashdifferent RT schedules

ndashAim find optimal RT schedule for maximal palliation with

minimal toxicityneed for reirradiation

Thoracic symptoms

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 59

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz

Cancer

2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 60

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz Chow Hartsell Konski Cancer 2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 61

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemoptysis

bull Fig2 toux

733 689

812 802

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 62

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig3 doul thor 321 279

535 482

Cough

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 63

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 4 overall symptom burden

575 519

648 638

Thoracic pain

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 64

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 5 survie 1a

Cutoff (sensitivity analysis) BED[10] 35Gy vs LD

100 162

555 609

Overall symptom burden

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 65

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cutoff BED[10] 35Gy vs LD

265 217

Overall survival at 1y

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 66

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 7 Tox dysphagie

Cutoff BED[10] 30Gy vs LD

205 149

about x 2

Toxicity (dysphagia)

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 67

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomized trial 250 patients (Falk BMJ 2002)

bull Locally advanced non resectable NSCLC with minimal thoracic symptoms

bull Immediate vs delayed RT (at symptom onset)

bull In delayed arm 56 of patients died without RT

bull No difference in QOL odr OS

bull More acute toxicity in immediate RT arm

Randomized trial (Sundstrom Radiother Oncol 2005)

bull Advanced NSCLC

bull 2 RT schedules (5x4Gy vs 2x85 Gy) immediate RT

bull Stratification according to presenceabsence of thoracic symptoms

bull In asymptomatic patients no long term symptom control but important dysphagia

Timing

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 68

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull in 97 malignant

bull in 5-10 of lung cancer patients

bull Histology (exclude benign disease RT-chemosensible tumours

bull Generally spontanous improvement of symptoms by formation of collaterals

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 69

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Treatment

1 symptomatic

bull steroids

bull diuretics

bull Elevation of headthorax

2 causal bull chemotherapy (SCLC

lymphomas germinal tumours)

bull Endovascular stent placement

bull radiotherapy Palliative care in lung cancer ACCP

evidence- based clinical practice guidelines

(2nd edition)

Kvale Chest 2007

Superior vena cava syndrome

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

Radiotherapy

bull Mostly clinical response within 72 h

bull Complete clinical response at 2 w in 78 of patients with SCLC

and 63 of patients with NSCLC

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 72

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 73

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duhamel Atlas clinique des maladies

des voies aeacuteriennes Elsevier

wwwupmccancercenterscom

Endobronchial brachytherapy

Cochrane analysis (Cardona The Cochrane

Library 2008)

bull No improved

symptom relief by

addition of

endobronchial

brachytherapy to

EBRT

bull Indicated in selected

patients pretreated

by EBRT with

central

endobronchial

obstruction

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 74

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Ozkok Lung Cancer 2008

Endobronchial brachytherapy

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Take home lung cancer

Dosefractionation

bull Minimum 10x3 Gy 5xw or equivalent

ndash better symptom control and better overall survival

ndash But more toxicity

bull Short schedule for symptom control and limited toxicity

ndashPoor performance status limited life expectancy

Timing

bull RT at the moment of symptom onset

bull No place for bdquoprophylactic palliative RTldquo according to evidence based guidelines

ndashExceptions

bull Young patient good PS aim of local control

bull Imminent symptoms (superior vena cava syndrome central airway obstruction

Rodrigues Pract Rad Oncol 2011

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 80

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Homs Eur J CancerLancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 83

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 84

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 90

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 99

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Scoccianti Radiother Oncol 2012

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SRO Tutorial Palliative Care ndash Palliative Radiotherapy 29

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 30

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Biphosphonates

bull Several prospective studies on concurrent EBRT and

biphosphonates successful pain relief promotion of re-

ossification of damaged bone acceptable risk of toxicity

bull Not shown that combination better than EBRT alone for

pain relief

bull Recommendation prospective trial on optimum RT

fractionation EBRT versus radionuclides dose and

duration of biphosphonates and scheduling

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 31

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 32

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Denosumab

Lipton Curr Opp Supp Pall Care 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 33

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lipton Curr Opp Supp

Pall Care 2011

Denosumab versus

Zoledronate

Prevention of SREs (path fracture RT or OP to bone

spinal cord compression)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 34

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Breast

superior

Prostate

superior

Other solid

tumors or

multiple

myeloma

non inferior

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 35

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Vertebroplastykyphoplasty

bull No prospective data to suggest

that vertkyph obviates the

need for EBRT in painful bone

met

bull Small series of patients treated

by vertkyph plus EBRT

bull Recommendation prospective

trials on patient selection

efficacy toxicity and timing of

vertkyph and RT

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 36

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 37

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Non inferiority study

bull 272 patients randomized

Neuropathic pain

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 38

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 39

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 40

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Spinal cord compression

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 41

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 42

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 43

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Patchell Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 44

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

RT short versus

long course

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 45

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 46

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 47

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 48

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 49

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 50

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull SRO tutorial CNS PD Dr A Pica

bull ScocciantiRicardi Radiother Oncol 2012 Review

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 51

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemorrhage

bull Bleeding in 6-10 of patients with advanced

cancer (Pereira et al Topics in Palliative Care Vol 4 New York

Oxford University Press 2000)

bull haemoptysis

bull haematemesis

bull haematocheziamelaena

bull vaginal bleeding

bull haematuria

bull bleeding in ulcerated skin lesions

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 52

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Mechanisms of haemostatic radiotherapy

bull Sparse literature

bull Coagulation activationsup1

ndash Oxydative endothelial damage

ndash Activation of thrombocytes

ndash Activation of inflammation

bull Long term anti-angiogenetic

sup1 Hallahan et al Oncology (Huntingt) 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 53

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Prostate cancer

bull Reduction of pain and bleeding in hormone refractory

prostate cancer (Kynaston Br J Urol 1990 Kawakami Nippon

Hinyokika Gakkai Zasshi 1993 Kalapurakal Int J Radiat Oncol Biol Phys

2003)

bull 100 improvement in patients with important hematuria (Carlton J Urol 1972)

Bladder cancer (Srinivasan et al Clin Oncol (R Coll Radiol) 1994)

bull 17 Gy in 2 fractions3 days 59 clearance of hematuria

bull 45 Gy in 12 fractions26 days 16 clearance of

hematuria

bull Selection by performance status Palliation (pain and

hematuria) better with hypofractionated RT worse

survival

bull No important side effects

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 54

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung cancer

bull Control of hemoptysis in up to 80 of patients (Brundage

Can J Oncol 1996 Medical Research Council Lung Cancer Working Party

Br J Cancer 1992 Hoskin in Doyle et al Second Edition New York

Oxford University Press 1998 Langendijk Int J Radiat Oncol Biol Phys

2000)

bull Optimal dosefractionation

ndash Hypofractionated RT seems to be equally effective to multiple

fractions (Rees Clin Oncol (R Coll Radiol) 1997 Sundstrom JCO

2004 Phase III Stevens Australas Radiol 1995 Phase III studies of

the MRC (s above)

ndash 10 Gy Single fraction equally effective to multiple fractions less

toxic (Hoskin in Doyle et al Second Edition New York Oxford

University Press 1998 Medical Research Council Lung Cancer

Working Party Br J Cancer 1992)

ndash Mostly total dose of around 20 Gy (multiple fractions) or 8 Gy

single fraction recommended

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 55

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Van Lonkhuijzen

Radiother Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 56

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gynaecologic tumours

bull Cf review van Lonkhuijzen Radiother Oncol 2011

bull Consider intracavitary HDR brachytherapy

Rectal cancer

bull Up to 85 control of rectal bleeding (Hoskin in Doyle et al Second Edition New York Oxford University Press 1998)

Kaposi sarcoma

bull Good palliation for pain bleeding or edema TD 15-40 Gy SD 2 Gy gt90 response 70 complete remission (Review Becker et al Onkologie 2006)

Skin tumours (Miller in Doyle Oxford Textbook of Palliative Medicine New York Oxford University Press 1993)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 57

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duration of treatment effect

Lung cancer

bull Median duration of palliation 50 of remaining life span (30 Gy10d

27 Gy6d 17 Gy2 fract1w apart) (Medical Research Council Br J

Cancer 1991)

bull 1 fract 10 Gy vs 2 fract 85 Gy more patients need repeat RT (Medical Research Council Lung Cancer Working Party Br J Cancer 1992)

bull 417 pat need repeat RT within 3 m after 1x10 Gy (Scolaro Radiol

Med 1995)

Rec ovarian cancer

bull Median duration of palliation 4 m in 90 of patients until death (Corn Cancer 1994)

Cervical endometrial cancer

bull In 50 of patients pall Effect until death with 1-2x10 Gy

ndash Halle IJROBP 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 58

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull RT effective for improvement of

ndashThoracic symptoms (haemoptysis cough thoracic pain

dyspnoea airway obstruction) (Sirzeacuten Acta Oncol 2003 and others)

ndashQOL in about 13 of patients (Langendijk IJROBP 2000)

RT schedules

bull Systematic review (Fairchild JCO 264001-4011 2008)

ndash13 randomized trials 3473 patients

ndashdifferent RT schedules

ndashAim find optimal RT schedule for maximal palliation with

minimal toxicityneed for reirradiation

Thoracic symptoms

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 59

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz

Cancer

2007

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz Chow Hartsell Konski Cancer 2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 61

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemoptysis

bull Fig2 toux

733 689

812 802

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 62

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig3 doul thor 321 279

535 482

Cough

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 63

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 4 overall symptom burden

575 519

648 638

Thoracic pain

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 64

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 5 survie 1a

Cutoff (sensitivity analysis) BED[10] 35Gy vs LD

100 162

555 609

Overall symptom burden

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 65

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cutoff BED[10] 35Gy vs LD

265 217

Overall survival at 1y

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 66

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 7 Tox dysphagie

Cutoff BED[10] 30Gy vs LD

205 149

about x 2

Toxicity (dysphagia)

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 67

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomized trial 250 patients (Falk BMJ 2002)

bull Locally advanced non resectable NSCLC with minimal thoracic symptoms

bull Immediate vs delayed RT (at symptom onset)

bull In delayed arm 56 of patients died without RT

bull No difference in QOL odr OS

bull More acute toxicity in immediate RT arm

Randomized trial (Sundstrom Radiother Oncol 2005)

bull Advanced NSCLC

bull 2 RT schedules (5x4Gy vs 2x85 Gy) immediate RT

bull Stratification according to presenceabsence of thoracic symptoms

bull In asymptomatic patients no long term symptom control but important dysphagia

Timing

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 68

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull in 97 malignant

bull in 5-10 of lung cancer patients

bull Histology (exclude benign disease RT-chemosensible tumours

bull Generally spontanous improvement of symptoms by formation of collaterals

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 69

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Treatment

1 symptomatic

bull steroids

bull diuretics

bull Elevation of headthorax

2 causal bull chemotherapy (SCLC

lymphomas germinal tumours)

bull Endovascular stent placement

bull radiotherapy Palliative care in lung cancer ACCP

evidence- based clinical practice guidelines

(2nd edition)

Kvale Chest 2007

Superior vena cava syndrome

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

Radiotherapy

bull Mostly clinical response within 72 h

bull Complete clinical response at 2 w in 78 of patients with SCLC

and 63 of patients with NSCLC

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 72

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 73

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duhamel Atlas clinique des maladies

des voies aeacuteriennes Elsevier

wwwupmccancercenterscom

Endobronchial brachytherapy

Cochrane analysis (Cardona The Cochrane

Library 2008)

bull No improved

symptom relief by

addition of

endobronchial

brachytherapy to

EBRT

bull Indicated in selected

patients pretreated

by EBRT with

central

endobronchial

obstruction

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 74

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Ozkok Lung Cancer 2008

Endobronchial brachytherapy

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Take home lung cancer

Dosefractionation

bull Minimum 10x3 Gy 5xw or equivalent

ndash better symptom control and better overall survival

ndash But more toxicity

bull Short schedule for symptom control and limited toxicity

ndashPoor performance status limited life expectancy

Timing

bull RT at the moment of symptom onset

bull No place for bdquoprophylactic palliative RTldquo according to evidence based guidelines

ndashExceptions

bull Young patient good PS aim of local control

bull Imminent symptoms (superior vena cava syndrome central airway obstruction

Rodrigues Pract Rad Oncol 2011

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 80

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 82

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 83

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 84

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 85

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 90

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 98

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Scoccianti Radiother Oncol 2012

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SRO Tutorial Palliative Care ndash Palliative Radiotherapy 30

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Biphosphonates

bull Several prospective studies on concurrent EBRT and

biphosphonates successful pain relief promotion of re-

ossification of damaged bone acceptable risk of toxicity

bull Not shown that combination better than EBRT alone for

pain relief

bull Recommendation prospective trial on optimum RT

fractionation EBRT versus radionuclides dose and

duration of biphosphonates and scheduling

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 31

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 32

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Denosumab

Lipton Curr Opp Supp Pall Care 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 33

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lipton Curr Opp Supp

Pall Care 2011

Denosumab versus

Zoledronate

Prevention of SREs (path fracture RT or OP to bone

spinal cord compression)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 34

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Breast

superior

Prostate

superior

Other solid

tumors or

multiple

myeloma

non inferior

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 35

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Vertebroplastykyphoplasty

bull No prospective data to suggest

that vertkyph obviates the

need for EBRT in painful bone

met

bull Small series of patients treated

by vertkyph plus EBRT

bull Recommendation prospective

trials on patient selection

efficacy toxicity and timing of

vertkyph and RT

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 36

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 37

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Non inferiority study

bull 272 patients randomized

Neuropathic pain

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 38

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 39

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 40

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Spinal cord compression

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 41

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 42

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 43

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Patchell Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 44

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

RT short versus

long course

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 45

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 46

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 47

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 48

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 49

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 50

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull SRO tutorial CNS PD Dr A Pica

bull ScocciantiRicardi Radiother Oncol 2012 Review

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 51

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemorrhage

bull Bleeding in 6-10 of patients with advanced

cancer (Pereira et al Topics in Palliative Care Vol 4 New York

Oxford University Press 2000)

bull haemoptysis

bull haematemesis

bull haematocheziamelaena

bull vaginal bleeding

bull haematuria

bull bleeding in ulcerated skin lesions

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 52

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Mechanisms of haemostatic radiotherapy

bull Sparse literature

bull Coagulation activationsup1

ndash Oxydative endothelial damage

ndash Activation of thrombocytes

ndash Activation of inflammation

bull Long term anti-angiogenetic

sup1 Hallahan et al Oncology (Huntingt) 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 53

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Prostate cancer

bull Reduction of pain and bleeding in hormone refractory

prostate cancer (Kynaston Br J Urol 1990 Kawakami Nippon

Hinyokika Gakkai Zasshi 1993 Kalapurakal Int J Radiat Oncol Biol Phys

2003)

bull 100 improvement in patients with important hematuria (Carlton J Urol 1972)

Bladder cancer (Srinivasan et al Clin Oncol (R Coll Radiol) 1994)

bull 17 Gy in 2 fractions3 days 59 clearance of hematuria

bull 45 Gy in 12 fractions26 days 16 clearance of

hematuria

bull Selection by performance status Palliation (pain and

hematuria) better with hypofractionated RT worse

survival

bull No important side effects

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 54

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung cancer

bull Control of hemoptysis in up to 80 of patients (Brundage

Can J Oncol 1996 Medical Research Council Lung Cancer Working Party

Br J Cancer 1992 Hoskin in Doyle et al Second Edition New York

Oxford University Press 1998 Langendijk Int J Radiat Oncol Biol Phys

2000)

bull Optimal dosefractionation

ndash Hypofractionated RT seems to be equally effective to multiple

fractions (Rees Clin Oncol (R Coll Radiol) 1997 Sundstrom JCO

2004 Phase III Stevens Australas Radiol 1995 Phase III studies of

the MRC (s above)

ndash 10 Gy Single fraction equally effective to multiple fractions less

toxic (Hoskin in Doyle et al Second Edition New York Oxford

University Press 1998 Medical Research Council Lung Cancer

Working Party Br J Cancer 1992)

ndash Mostly total dose of around 20 Gy (multiple fractions) or 8 Gy

single fraction recommended

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 55

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Van Lonkhuijzen

Radiother Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 56

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gynaecologic tumours

bull Cf review van Lonkhuijzen Radiother Oncol 2011

bull Consider intracavitary HDR brachytherapy

Rectal cancer

bull Up to 85 control of rectal bleeding (Hoskin in Doyle et al Second Edition New York Oxford University Press 1998)

Kaposi sarcoma

bull Good palliation for pain bleeding or edema TD 15-40 Gy SD 2 Gy gt90 response 70 complete remission (Review Becker et al Onkologie 2006)

Skin tumours (Miller in Doyle Oxford Textbook of Palliative Medicine New York Oxford University Press 1993)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 57

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duration of treatment effect

Lung cancer

bull Median duration of palliation 50 of remaining life span (30 Gy10d

27 Gy6d 17 Gy2 fract1w apart) (Medical Research Council Br J

Cancer 1991)

bull 1 fract 10 Gy vs 2 fract 85 Gy more patients need repeat RT (Medical Research Council Lung Cancer Working Party Br J Cancer 1992)

bull 417 pat need repeat RT within 3 m after 1x10 Gy (Scolaro Radiol

Med 1995)

Rec ovarian cancer

bull Median duration of palliation 4 m in 90 of patients until death (Corn Cancer 1994)

Cervical endometrial cancer

bull In 50 of patients pall Effect until death with 1-2x10 Gy

ndash Halle IJROBP 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 58

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull RT effective for improvement of

ndashThoracic symptoms (haemoptysis cough thoracic pain

dyspnoea airway obstruction) (Sirzeacuten Acta Oncol 2003 and others)

ndashQOL in about 13 of patients (Langendijk IJROBP 2000)

RT schedules

bull Systematic review (Fairchild JCO 264001-4011 2008)

ndash13 randomized trials 3473 patients

ndashdifferent RT schedules

ndashAim find optimal RT schedule for maximal palliation with

minimal toxicityneed for reirradiation

Thoracic symptoms

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 59

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz

Cancer

2007

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz Chow Hartsell Konski Cancer 2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 61

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemoptysis

bull Fig2 toux

733 689

812 802

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 62

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig3 doul thor 321 279

535 482

Cough

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 63

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 4 overall symptom burden

575 519

648 638

Thoracic pain

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 64

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 5 survie 1a

Cutoff (sensitivity analysis) BED[10] 35Gy vs LD

100 162

555 609

Overall symptom burden

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 65

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cutoff BED[10] 35Gy vs LD

265 217

Overall survival at 1y

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 66

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 7 Tox dysphagie

Cutoff BED[10] 30Gy vs LD

205 149

about x 2

Toxicity (dysphagia)

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 67

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomized trial 250 patients (Falk BMJ 2002)

bull Locally advanced non resectable NSCLC with minimal thoracic symptoms

bull Immediate vs delayed RT (at symptom onset)

bull In delayed arm 56 of patients died without RT

bull No difference in QOL odr OS

bull More acute toxicity in immediate RT arm

Randomized trial (Sundstrom Radiother Oncol 2005)

bull Advanced NSCLC

bull 2 RT schedules (5x4Gy vs 2x85 Gy) immediate RT

bull Stratification according to presenceabsence of thoracic symptoms

bull In asymptomatic patients no long term symptom control but important dysphagia

Timing

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 68

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull in 97 malignant

bull in 5-10 of lung cancer patients

bull Histology (exclude benign disease RT-chemosensible tumours

bull Generally spontanous improvement of symptoms by formation of collaterals

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 69

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Treatment

1 symptomatic

bull steroids

bull diuretics

bull Elevation of headthorax

2 causal bull chemotherapy (SCLC

lymphomas germinal tumours)

bull Endovascular stent placement

bull radiotherapy Palliative care in lung cancer ACCP

evidence- based clinical practice guidelines

(2nd edition)

Kvale Chest 2007

Superior vena cava syndrome

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

Radiotherapy

bull Mostly clinical response within 72 h

bull Complete clinical response at 2 w in 78 of patients with SCLC

and 63 of patients with NSCLC

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 72

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 73

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duhamel Atlas clinique des maladies

des voies aeacuteriennes Elsevier

wwwupmccancercenterscom

Endobronchial brachytherapy

Cochrane analysis (Cardona The Cochrane

Library 2008)

bull No improved

symptom relief by

addition of

endobronchial

brachytherapy to

EBRT

bull Indicated in selected

patients pretreated

by EBRT with

central

endobronchial

obstruction

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 74

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Ozkok Lung Cancer 2008

Endobronchial brachytherapy

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Take home lung cancer

Dosefractionation

bull Minimum 10x3 Gy 5xw or equivalent

ndash better symptom control and better overall survival

ndash But more toxicity

bull Short schedule for symptom control and limited toxicity

ndashPoor performance status limited life expectancy

Timing

bull RT at the moment of symptom onset

bull No place for bdquoprophylactic palliative RTldquo according to evidence based guidelines

ndashExceptions

bull Young patient good PS aim of local control

bull Imminent symptoms (superior vena cava syndrome central airway obstruction

Rodrigues Pract Rad Oncol 2011

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 80

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 81

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 82

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 83

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 84

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 90

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 98

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 99

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Scoccianti Radiother Oncol 2012

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 32

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Denosumab

Lipton Curr Opp Supp Pall Care 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 33

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lipton Curr Opp Supp

Pall Care 2011

Denosumab versus

Zoledronate

Prevention of SREs (path fracture RT or OP to bone

spinal cord compression)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 34

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Breast

superior

Prostate

superior

Other solid

tumors or

multiple

myeloma

non inferior

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 35

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Vertebroplastykyphoplasty

bull No prospective data to suggest

that vertkyph obviates the

need for EBRT in painful bone

met

bull Small series of patients treated

by vertkyph plus EBRT

bull Recommendation prospective

trials on patient selection

efficacy toxicity and timing of

vertkyph and RT

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 36

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 37

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Non inferiority study

bull 272 patients randomized

Neuropathic pain

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 38

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 39

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 40

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Spinal cord compression

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 41

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 42

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 43

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Patchell Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 44

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

RT short versus

long course

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 45

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 46

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 47

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 48

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 49

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 50

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull SRO tutorial CNS PD Dr A Pica

bull ScocciantiRicardi Radiother Oncol 2012 Review

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 51

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemorrhage

bull Bleeding in 6-10 of patients with advanced

cancer (Pereira et al Topics in Palliative Care Vol 4 New York

Oxford University Press 2000)

bull haemoptysis

bull haematemesis

bull haematocheziamelaena

bull vaginal bleeding

bull haematuria

bull bleeding in ulcerated skin lesions

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 52

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Mechanisms of haemostatic radiotherapy

bull Sparse literature

bull Coagulation activationsup1

ndash Oxydative endothelial damage

ndash Activation of thrombocytes

ndash Activation of inflammation

bull Long term anti-angiogenetic

sup1 Hallahan et al Oncology (Huntingt) 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 53

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Prostate cancer

bull Reduction of pain and bleeding in hormone refractory

prostate cancer (Kynaston Br J Urol 1990 Kawakami Nippon

Hinyokika Gakkai Zasshi 1993 Kalapurakal Int J Radiat Oncol Biol Phys

2003)

bull 100 improvement in patients with important hematuria (Carlton J Urol 1972)

Bladder cancer (Srinivasan et al Clin Oncol (R Coll Radiol) 1994)

bull 17 Gy in 2 fractions3 days 59 clearance of hematuria

bull 45 Gy in 12 fractions26 days 16 clearance of

hematuria

bull Selection by performance status Palliation (pain and

hematuria) better with hypofractionated RT worse

survival

bull No important side effects

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 54

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung cancer

bull Control of hemoptysis in up to 80 of patients (Brundage

Can J Oncol 1996 Medical Research Council Lung Cancer Working Party

Br J Cancer 1992 Hoskin in Doyle et al Second Edition New York

Oxford University Press 1998 Langendijk Int J Radiat Oncol Biol Phys

2000)

bull Optimal dosefractionation

ndash Hypofractionated RT seems to be equally effective to multiple

fractions (Rees Clin Oncol (R Coll Radiol) 1997 Sundstrom JCO

2004 Phase III Stevens Australas Radiol 1995 Phase III studies of

the MRC (s above)

ndash 10 Gy Single fraction equally effective to multiple fractions less

toxic (Hoskin in Doyle et al Second Edition New York Oxford

University Press 1998 Medical Research Council Lung Cancer

Working Party Br J Cancer 1992)

ndash Mostly total dose of around 20 Gy (multiple fractions) or 8 Gy

single fraction recommended

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 55

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Van Lonkhuijzen

Radiother Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 56

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gynaecologic tumours

bull Cf review van Lonkhuijzen Radiother Oncol 2011

bull Consider intracavitary HDR brachytherapy

Rectal cancer

bull Up to 85 control of rectal bleeding (Hoskin in Doyle et al Second Edition New York Oxford University Press 1998)

Kaposi sarcoma

bull Good palliation for pain bleeding or edema TD 15-40 Gy SD 2 Gy gt90 response 70 complete remission (Review Becker et al Onkologie 2006)

Skin tumours (Miller in Doyle Oxford Textbook of Palliative Medicine New York Oxford University Press 1993)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 57

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duration of treatment effect

Lung cancer

bull Median duration of palliation 50 of remaining life span (30 Gy10d

27 Gy6d 17 Gy2 fract1w apart) (Medical Research Council Br J

Cancer 1991)

bull 1 fract 10 Gy vs 2 fract 85 Gy more patients need repeat RT (Medical Research Council Lung Cancer Working Party Br J Cancer 1992)

bull 417 pat need repeat RT within 3 m after 1x10 Gy (Scolaro Radiol

Med 1995)

Rec ovarian cancer

bull Median duration of palliation 4 m in 90 of patients until death (Corn Cancer 1994)

Cervical endometrial cancer

bull In 50 of patients pall Effect until death with 1-2x10 Gy

ndash Halle IJROBP 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 58

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull RT effective for improvement of

ndashThoracic symptoms (haemoptysis cough thoracic pain

dyspnoea airway obstruction) (Sirzeacuten Acta Oncol 2003 and others)

ndashQOL in about 13 of patients (Langendijk IJROBP 2000)

RT schedules

bull Systematic review (Fairchild JCO 264001-4011 2008)

ndash13 randomized trials 3473 patients

ndashdifferent RT schedules

ndashAim find optimal RT schedule for maximal palliation with

minimal toxicityneed for reirradiation

Thoracic symptoms

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 59

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz

Cancer

2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 60

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz Chow Hartsell Konski Cancer 2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 61

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemoptysis

bull Fig2 toux

733 689

812 802

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 62

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig3 doul thor 321 279

535 482

Cough

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 63

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 4 overall symptom burden

575 519

648 638

Thoracic pain

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 64

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 5 survie 1a

Cutoff (sensitivity analysis) BED[10] 35Gy vs LD

100 162

555 609

Overall symptom burden

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 65

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cutoff BED[10] 35Gy vs LD

265 217

Overall survival at 1y

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 66

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 7 Tox dysphagie

Cutoff BED[10] 30Gy vs LD

205 149

about x 2

Toxicity (dysphagia)

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 67

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomized trial 250 patients (Falk BMJ 2002)

bull Locally advanced non resectable NSCLC with minimal thoracic symptoms

bull Immediate vs delayed RT (at symptom onset)

bull In delayed arm 56 of patients died without RT

bull No difference in QOL odr OS

bull More acute toxicity in immediate RT arm

Randomized trial (Sundstrom Radiother Oncol 2005)

bull Advanced NSCLC

bull 2 RT schedules (5x4Gy vs 2x85 Gy) immediate RT

bull Stratification according to presenceabsence of thoracic symptoms

bull In asymptomatic patients no long term symptom control but important dysphagia

Timing

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 68

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull in 97 malignant

bull in 5-10 of lung cancer patients

bull Histology (exclude benign disease RT-chemosensible tumours

bull Generally spontanous improvement of symptoms by formation of collaterals

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 69

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Treatment

1 symptomatic

bull steroids

bull diuretics

bull Elevation of headthorax

2 causal bull chemotherapy (SCLC

lymphomas germinal tumours)

bull Endovascular stent placement

bull radiotherapy Palliative care in lung cancer ACCP

evidence- based clinical practice guidelines

(2nd edition)

Kvale Chest 2007

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 70

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

Radiotherapy

bull Mostly clinical response within 72 h

bull Complete clinical response at 2 w in 78 of patients with SCLC

and 63 of patients with NSCLC

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 71

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 72

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 73

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duhamel Atlas clinique des maladies

des voies aeacuteriennes Elsevier

wwwupmccancercenterscom

Endobronchial brachytherapy

Cochrane analysis (Cardona The Cochrane

Library 2008)

bull No improved

symptom relief by

addition of

endobronchial

brachytherapy to

EBRT

bull Indicated in selected

patients pretreated

by EBRT with

central

endobronchial

obstruction

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 74

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Ozkok Lung Cancer 2008

Endobronchial brachytherapy

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 75

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Take home lung cancer

Dosefractionation

bull Minimum 10x3 Gy 5xw or equivalent

ndash better symptom control and better overall survival

ndash But more toxicity

bull Short schedule for symptom control and limited toxicity

ndashPoor performance status limited life expectancy

Timing

bull RT at the moment of symptom onset

bull No place for bdquoprophylactic palliative RTldquo according to evidence based guidelines

ndashExceptions

bull Young patient good PS aim of local control

bull Imminent symptoms (superior vena cava syndrome central airway obstruction

Rodrigues Pract Rad Oncol 2011

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 77

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 80

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 81

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 82

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 83

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 84

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 85

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 90

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 98

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 99

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Scoccianti Radiother Oncol 2012

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SRO Tutorial Palliative Care ndash Palliative Radiotherapy 32

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Denosumab

Lipton Curr Opp Supp Pall Care 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 33

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lipton Curr Opp Supp

Pall Care 2011

Denosumab versus

Zoledronate

Prevention of SREs (path fracture RT or OP to bone

spinal cord compression)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 34

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Breast

superior

Prostate

superior

Other solid

tumors or

multiple

myeloma

non inferior

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 35

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Vertebroplastykyphoplasty

bull No prospective data to suggest

that vertkyph obviates the

need for EBRT in painful bone

met

bull Small series of patients treated

by vertkyph plus EBRT

bull Recommendation prospective

trials on patient selection

efficacy toxicity and timing of

vertkyph and RT

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 36

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 37

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Non inferiority study

bull 272 patients randomized

Neuropathic pain

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 38

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 39

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 40

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Spinal cord compression

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 41

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 42

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 43

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Patchell Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 44

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

RT short versus

long course

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 45

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 46

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 47

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 48

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 49

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 50

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull SRO tutorial CNS PD Dr A Pica

bull ScocciantiRicardi Radiother Oncol 2012 Review

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 51

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemorrhage

bull Bleeding in 6-10 of patients with advanced

cancer (Pereira et al Topics in Palliative Care Vol 4 New York

Oxford University Press 2000)

bull haemoptysis

bull haematemesis

bull haematocheziamelaena

bull vaginal bleeding

bull haematuria

bull bleeding in ulcerated skin lesions

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 52

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Mechanisms of haemostatic radiotherapy

bull Sparse literature

bull Coagulation activationsup1

ndash Oxydative endothelial damage

ndash Activation of thrombocytes

ndash Activation of inflammation

bull Long term anti-angiogenetic

sup1 Hallahan et al Oncology (Huntingt) 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 53

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Prostate cancer

bull Reduction of pain and bleeding in hormone refractory

prostate cancer (Kynaston Br J Urol 1990 Kawakami Nippon

Hinyokika Gakkai Zasshi 1993 Kalapurakal Int J Radiat Oncol Biol Phys

2003)

bull 100 improvement in patients with important hematuria (Carlton J Urol 1972)

Bladder cancer (Srinivasan et al Clin Oncol (R Coll Radiol) 1994)

bull 17 Gy in 2 fractions3 days 59 clearance of hematuria

bull 45 Gy in 12 fractions26 days 16 clearance of

hematuria

bull Selection by performance status Palliation (pain and

hematuria) better with hypofractionated RT worse

survival

bull No important side effects

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 54

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung cancer

bull Control of hemoptysis in up to 80 of patients (Brundage

Can J Oncol 1996 Medical Research Council Lung Cancer Working Party

Br J Cancer 1992 Hoskin in Doyle et al Second Edition New York

Oxford University Press 1998 Langendijk Int J Radiat Oncol Biol Phys

2000)

bull Optimal dosefractionation

ndash Hypofractionated RT seems to be equally effective to multiple

fractions (Rees Clin Oncol (R Coll Radiol) 1997 Sundstrom JCO

2004 Phase III Stevens Australas Radiol 1995 Phase III studies of

the MRC (s above)

ndash 10 Gy Single fraction equally effective to multiple fractions less

toxic (Hoskin in Doyle et al Second Edition New York Oxford

University Press 1998 Medical Research Council Lung Cancer

Working Party Br J Cancer 1992)

ndash Mostly total dose of around 20 Gy (multiple fractions) or 8 Gy

single fraction recommended

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 55

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Van Lonkhuijzen

Radiother Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 56

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gynaecologic tumours

bull Cf review van Lonkhuijzen Radiother Oncol 2011

bull Consider intracavitary HDR brachytherapy

Rectal cancer

bull Up to 85 control of rectal bleeding (Hoskin in Doyle et al Second Edition New York Oxford University Press 1998)

Kaposi sarcoma

bull Good palliation for pain bleeding or edema TD 15-40 Gy SD 2 Gy gt90 response 70 complete remission (Review Becker et al Onkologie 2006)

Skin tumours (Miller in Doyle Oxford Textbook of Palliative Medicine New York Oxford University Press 1993)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 57

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duration of treatment effect

Lung cancer

bull Median duration of palliation 50 of remaining life span (30 Gy10d

27 Gy6d 17 Gy2 fract1w apart) (Medical Research Council Br J

Cancer 1991)

bull 1 fract 10 Gy vs 2 fract 85 Gy more patients need repeat RT (Medical Research Council Lung Cancer Working Party Br J Cancer 1992)

bull 417 pat need repeat RT within 3 m after 1x10 Gy (Scolaro Radiol

Med 1995)

Rec ovarian cancer

bull Median duration of palliation 4 m in 90 of patients until death (Corn Cancer 1994)

Cervical endometrial cancer

bull In 50 of patients pall Effect until death with 1-2x10 Gy

ndash Halle IJROBP 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 58

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull RT effective for improvement of

ndashThoracic symptoms (haemoptysis cough thoracic pain

dyspnoea airway obstruction) (Sirzeacuten Acta Oncol 2003 and others)

ndashQOL in about 13 of patients (Langendijk IJROBP 2000)

RT schedules

bull Systematic review (Fairchild JCO 264001-4011 2008)

ndash13 randomized trials 3473 patients

ndashdifferent RT schedules

ndashAim find optimal RT schedule for maximal palliation with

minimal toxicityneed for reirradiation

Thoracic symptoms

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 59

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz

Cancer

2007

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz Chow Hartsell Konski Cancer 2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 61

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Haemoptysis

bull Fig2 toux

733 689

812 802

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 62

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig3 doul thor 321 279

535 482

Cough

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 63

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 4 overall symptom burden

575 519

648 638

Thoracic pain

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 64

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 5 survie 1a

Cutoff (sensitivity analysis) BED[10] 35Gy vs LD

100 162

555 609

Overall symptom burden

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 65

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cutoff BED[10] 35Gy vs LD

265 217

Overall survival at 1y

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 66

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 7 Tox dysphagie

Cutoff BED[10] 30Gy vs LD

205 149

about x 2

Toxicity (dysphagia)

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 67

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomized trial 250 patients (Falk BMJ 2002)

bull Locally advanced non resectable NSCLC with minimal thoracic symptoms

bull Immediate vs delayed RT (at symptom onset)

bull In delayed arm 56 of patients died without RT

bull No difference in QOL odr OS

bull More acute toxicity in immediate RT arm

Randomized trial (Sundstrom Radiother Oncol 2005)

bull Advanced NSCLC

bull 2 RT schedules (5x4Gy vs 2x85 Gy) immediate RT

bull Stratification according to presenceabsence of thoracic symptoms

bull In asymptomatic patients no long term symptom control but important dysphagia

Timing

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 68

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull in 97 malignant

bull in 5-10 of lung cancer patients

bull Histology (exclude benign disease RT-chemosensible tumours

bull Generally spontanous improvement of symptoms by formation of collaterals

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 69

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Treatment

1 symptomatic

bull steroids

bull diuretics

bull Elevation of headthorax

2 causal bull chemotherapy (SCLC

lymphomas germinal tumours)

bull Endovascular stent placement

bull radiotherapy Palliative care in lung cancer ACCP

evidence- based clinical practice guidelines

(2nd edition)

Kvale Chest 2007

Superior vena cava syndrome

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

Radiotherapy

bull Mostly clinical response within 72 h

bull Complete clinical response at 2 w in 78 of patients with SCLC

and 63 of patients with NSCLC

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 72

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 73

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duhamel Atlas clinique des maladies

des voies aeacuteriennes Elsevier

wwwupmccancercenterscom

Endobronchial brachytherapy

Cochrane analysis (Cardona The Cochrane

Library 2008)

bull No improved

symptom relief by

addition of

endobronchial

brachytherapy to

EBRT

bull Indicated in selected

patients pretreated

by EBRT with

central

endobronchial

obstruction

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 74

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Ozkok Lung Cancer 2008

Endobronchial brachytherapy

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Take home lung cancer

Dosefractionation

bull Minimum 10x3 Gy 5xw or equivalent

ndash better symptom control and better overall survival

ndash But more toxicity

bull Short schedule for symptom control and limited toxicity

ndashPoor performance status limited life expectancy

Timing

bull RT at the moment of symptom onset

bull No place for bdquoprophylactic palliative RTldquo according to evidence based guidelines

ndashExceptions

bull Young patient good PS aim of local control

bull Imminent symptoms (superior vena cava syndrome central airway obstruction

Rodrigues Pract Rad Oncol 2011

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 77

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 80

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 81

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 82

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 83

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 84

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 85

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 90

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 98

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Scoccianti Radiother Oncol 2012

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SRO Tutorial Palliative Care ndash Palliative Radiotherapy 33

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lipton Curr Opp Supp

Pall Care 2011

Denosumab versus

Zoledronate

Prevention of SREs (path fracture RT or OP to bone

spinal cord compression)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 34

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Breast

superior

Prostate

superior

Other solid

tumors or

multiple

myeloma

non inferior

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 35

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Vertebroplastykyphoplasty

bull No prospective data to suggest

that vertkyph obviates the

need for EBRT in painful bone

met

bull Small series of patients treated

by vertkyph plus EBRT

bull Recommendation prospective

trials on patient selection

efficacy toxicity and timing of

vertkyph and RT

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 36

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 37

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Non inferiority study

bull 272 patients randomized

Neuropathic pain

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 38

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 39

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 40

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Spinal cord compression

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 41

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 42

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 43

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Patchell Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 44

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

RT short versus

long course

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 45

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 46

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 47

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 48

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 49

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 50

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull SRO tutorial CNS PD Dr A Pica

bull ScocciantiRicardi Radiother Oncol 2012 Review

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 51

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemorrhage

bull Bleeding in 6-10 of patients with advanced

cancer (Pereira et al Topics in Palliative Care Vol 4 New York

Oxford University Press 2000)

bull haemoptysis

bull haematemesis

bull haematocheziamelaena

bull vaginal bleeding

bull haematuria

bull bleeding in ulcerated skin lesions

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 52

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Mechanisms of haemostatic radiotherapy

bull Sparse literature

bull Coagulation activationsup1

ndash Oxydative endothelial damage

ndash Activation of thrombocytes

ndash Activation of inflammation

bull Long term anti-angiogenetic

sup1 Hallahan et al Oncology (Huntingt) 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 53

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Prostate cancer

bull Reduction of pain and bleeding in hormone refractory

prostate cancer (Kynaston Br J Urol 1990 Kawakami Nippon

Hinyokika Gakkai Zasshi 1993 Kalapurakal Int J Radiat Oncol Biol Phys

2003)

bull 100 improvement in patients with important hematuria (Carlton J Urol 1972)

Bladder cancer (Srinivasan et al Clin Oncol (R Coll Radiol) 1994)

bull 17 Gy in 2 fractions3 days 59 clearance of hematuria

bull 45 Gy in 12 fractions26 days 16 clearance of

hematuria

bull Selection by performance status Palliation (pain and

hematuria) better with hypofractionated RT worse

survival

bull No important side effects

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 54

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung cancer

bull Control of hemoptysis in up to 80 of patients (Brundage

Can J Oncol 1996 Medical Research Council Lung Cancer Working Party

Br J Cancer 1992 Hoskin in Doyle et al Second Edition New York

Oxford University Press 1998 Langendijk Int J Radiat Oncol Biol Phys

2000)

bull Optimal dosefractionation

ndash Hypofractionated RT seems to be equally effective to multiple

fractions (Rees Clin Oncol (R Coll Radiol) 1997 Sundstrom JCO

2004 Phase III Stevens Australas Radiol 1995 Phase III studies of

the MRC (s above)

ndash 10 Gy Single fraction equally effective to multiple fractions less

toxic (Hoskin in Doyle et al Second Edition New York Oxford

University Press 1998 Medical Research Council Lung Cancer

Working Party Br J Cancer 1992)

ndash Mostly total dose of around 20 Gy (multiple fractions) or 8 Gy

single fraction recommended

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 55

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Van Lonkhuijzen

Radiother Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 56

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gynaecologic tumours

bull Cf review van Lonkhuijzen Radiother Oncol 2011

bull Consider intracavitary HDR brachytherapy

Rectal cancer

bull Up to 85 control of rectal bleeding (Hoskin in Doyle et al Second Edition New York Oxford University Press 1998)

Kaposi sarcoma

bull Good palliation for pain bleeding or edema TD 15-40 Gy SD 2 Gy gt90 response 70 complete remission (Review Becker et al Onkologie 2006)

Skin tumours (Miller in Doyle Oxford Textbook of Palliative Medicine New York Oxford University Press 1993)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 57

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duration of treatment effect

Lung cancer

bull Median duration of palliation 50 of remaining life span (30 Gy10d

27 Gy6d 17 Gy2 fract1w apart) (Medical Research Council Br J

Cancer 1991)

bull 1 fract 10 Gy vs 2 fract 85 Gy more patients need repeat RT (Medical Research Council Lung Cancer Working Party Br J Cancer 1992)

bull 417 pat need repeat RT within 3 m after 1x10 Gy (Scolaro Radiol

Med 1995)

Rec ovarian cancer

bull Median duration of palliation 4 m in 90 of patients until death (Corn Cancer 1994)

Cervical endometrial cancer

bull In 50 of patients pall Effect until death with 1-2x10 Gy

ndash Halle IJROBP 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 58

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull RT effective for improvement of

ndashThoracic symptoms (haemoptysis cough thoracic pain

dyspnoea airway obstruction) (Sirzeacuten Acta Oncol 2003 and others)

ndashQOL in about 13 of patients (Langendijk IJROBP 2000)

RT schedules

bull Systematic review (Fairchild JCO 264001-4011 2008)

ndash13 randomized trials 3473 patients

ndashdifferent RT schedules

ndashAim find optimal RT schedule for maximal palliation with

minimal toxicityneed for reirradiation

Thoracic symptoms

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 59

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz

Cancer

2007

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Lutz Chow Hartsell Konski Cancer 2007

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Haemoptysis

bull Fig2 toux

733 689

812 802

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 62

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig3 doul thor 321 279

535 482

Cough

Fairchild JCO 2008

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 4 overall symptom burden

575 519

648 638

Thoracic pain

Fairchild JCO 2008

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 5 survie 1a

Cutoff (sensitivity analysis) BED[10] 35Gy vs LD

100 162

555 609

Overall symptom burden

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 65

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cutoff BED[10] 35Gy vs LD

265 217

Overall survival at 1y

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 66

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 7 Tox dysphagie

Cutoff BED[10] 30Gy vs LD

205 149

about x 2

Toxicity (dysphagia)

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 67

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomized trial 250 patients (Falk BMJ 2002)

bull Locally advanced non resectable NSCLC with minimal thoracic symptoms

bull Immediate vs delayed RT (at symptom onset)

bull In delayed arm 56 of patients died without RT

bull No difference in QOL odr OS

bull More acute toxicity in immediate RT arm

Randomized trial (Sundstrom Radiother Oncol 2005)

bull Advanced NSCLC

bull 2 RT schedules (5x4Gy vs 2x85 Gy) immediate RT

bull Stratification according to presenceabsence of thoracic symptoms

bull In asymptomatic patients no long term symptom control but important dysphagia

Timing

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 68

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull in 97 malignant

bull in 5-10 of lung cancer patients

bull Histology (exclude benign disease RT-chemosensible tumours

bull Generally spontanous improvement of symptoms by formation of collaterals

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 69

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Treatment

1 symptomatic

bull steroids

bull diuretics

bull Elevation of headthorax

2 causal bull chemotherapy (SCLC

lymphomas germinal tumours)

bull Endovascular stent placement

bull radiotherapy Palliative care in lung cancer ACCP

evidence- based clinical practice guidelines

(2nd edition)

Kvale Chest 2007

Superior vena cava syndrome

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

Radiotherapy

bull Mostly clinical response within 72 h

bull Complete clinical response at 2 w in 78 of patients with SCLC

and 63 of patients with NSCLC

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duhamel Atlas clinique des maladies

des voies aeacuteriennes Elsevier

wwwupmccancercenterscom

Endobronchial brachytherapy

Cochrane analysis (Cardona The Cochrane

Library 2008)

bull No improved

symptom relief by

addition of

endobronchial

brachytherapy to

EBRT

bull Indicated in selected

patients pretreated

by EBRT with

central

endobronchial

obstruction

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 74

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Ozkok Lung Cancer 2008

Endobronchial brachytherapy

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Take home lung cancer

Dosefractionation

bull Minimum 10x3 Gy 5xw or equivalent

ndash better symptom control and better overall survival

ndash But more toxicity

bull Short schedule for symptom control and limited toxicity

ndashPoor performance status limited life expectancy

Timing

bull RT at the moment of symptom onset

bull No place for bdquoprophylactic palliative RTldquo according to evidence based guidelines

ndashExceptions

bull Young patient good PS aim of local control

bull Imminent symptoms (superior vena cava syndrome central airway obstruction

Rodrigues Pract Rad Oncol 2011

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 80

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Homs Eur J CancerLancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 83

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 84

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 90

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 98

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 99

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Scoccianti Radiother Oncol 2012

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SRO Tutorial Palliative Care ndash Palliative Radiotherapy 34

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Breast

superior

Prostate

superior

Other solid

tumors or

multiple

myeloma

non inferior

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 35

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Vertebroplastykyphoplasty

bull No prospective data to suggest

that vertkyph obviates the

need for EBRT in painful bone

met

bull Small series of patients treated

by vertkyph plus EBRT

bull Recommendation prospective

trials on patient selection

efficacy toxicity and timing of

vertkyph and RT

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 36

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 37

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Non inferiority study

bull 272 patients randomized

Neuropathic pain

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 38

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 39

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 40

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Spinal cord compression

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 41

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 42

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 43

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Patchell Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 44

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

RT short versus

long course

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 45

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 46

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 47

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 48

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 49

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 50

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull SRO tutorial CNS PD Dr A Pica

bull ScocciantiRicardi Radiother Oncol 2012 Review

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 51

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemorrhage

bull Bleeding in 6-10 of patients with advanced

cancer (Pereira et al Topics in Palliative Care Vol 4 New York

Oxford University Press 2000)

bull haemoptysis

bull haematemesis

bull haematocheziamelaena

bull vaginal bleeding

bull haematuria

bull bleeding in ulcerated skin lesions

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 52

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Mechanisms of haemostatic radiotherapy

bull Sparse literature

bull Coagulation activationsup1

ndash Oxydative endothelial damage

ndash Activation of thrombocytes

ndash Activation of inflammation

bull Long term anti-angiogenetic

sup1 Hallahan et al Oncology (Huntingt) 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 53

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Prostate cancer

bull Reduction of pain and bleeding in hormone refractory

prostate cancer (Kynaston Br J Urol 1990 Kawakami Nippon

Hinyokika Gakkai Zasshi 1993 Kalapurakal Int J Radiat Oncol Biol Phys

2003)

bull 100 improvement in patients with important hematuria (Carlton J Urol 1972)

Bladder cancer (Srinivasan et al Clin Oncol (R Coll Radiol) 1994)

bull 17 Gy in 2 fractions3 days 59 clearance of hematuria

bull 45 Gy in 12 fractions26 days 16 clearance of

hematuria

bull Selection by performance status Palliation (pain and

hematuria) better with hypofractionated RT worse

survival

bull No important side effects

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 54

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung cancer

bull Control of hemoptysis in up to 80 of patients (Brundage

Can J Oncol 1996 Medical Research Council Lung Cancer Working Party

Br J Cancer 1992 Hoskin in Doyle et al Second Edition New York

Oxford University Press 1998 Langendijk Int J Radiat Oncol Biol Phys

2000)

bull Optimal dosefractionation

ndash Hypofractionated RT seems to be equally effective to multiple

fractions (Rees Clin Oncol (R Coll Radiol) 1997 Sundstrom JCO

2004 Phase III Stevens Australas Radiol 1995 Phase III studies of

the MRC (s above)

ndash 10 Gy Single fraction equally effective to multiple fractions less

toxic (Hoskin in Doyle et al Second Edition New York Oxford

University Press 1998 Medical Research Council Lung Cancer

Working Party Br J Cancer 1992)

ndash Mostly total dose of around 20 Gy (multiple fractions) or 8 Gy

single fraction recommended

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 55

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Van Lonkhuijzen

Radiother Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 56

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gynaecologic tumours

bull Cf review van Lonkhuijzen Radiother Oncol 2011

bull Consider intracavitary HDR brachytherapy

Rectal cancer

bull Up to 85 control of rectal bleeding (Hoskin in Doyle et al Second Edition New York Oxford University Press 1998)

Kaposi sarcoma

bull Good palliation for pain bleeding or edema TD 15-40 Gy SD 2 Gy gt90 response 70 complete remission (Review Becker et al Onkologie 2006)

Skin tumours (Miller in Doyle Oxford Textbook of Palliative Medicine New York Oxford University Press 1993)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 57

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duration of treatment effect

Lung cancer

bull Median duration of palliation 50 of remaining life span (30 Gy10d

27 Gy6d 17 Gy2 fract1w apart) (Medical Research Council Br J

Cancer 1991)

bull 1 fract 10 Gy vs 2 fract 85 Gy more patients need repeat RT (Medical Research Council Lung Cancer Working Party Br J Cancer 1992)

bull 417 pat need repeat RT within 3 m after 1x10 Gy (Scolaro Radiol

Med 1995)

Rec ovarian cancer

bull Median duration of palliation 4 m in 90 of patients until death (Corn Cancer 1994)

Cervical endometrial cancer

bull In 50 of patients pall Effect until death with 1-2x10 Gy

ndash Halle IJROBP 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 58

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull RT effective for improvement of

ndashThoracic symptoms (haemoptysis cough thoracic pain

dyspnoea airway obstruction) (Sirzeacuten Acta Oncol 2003 and others)

ndashQOL in about 13 of patients (Langendijk IJROBP 2000)

RT schedules

bull Systematic review (Fairchild JCO 264001-4011 2008)

ndash13 randomized trials 3473 patients

ndashdifferent RT schedules

ndashAim find optimal RT schedule for maximal palliation with

minimal toxicityneed for reirradiation

Thoracic symptoms

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 59

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz

Cancer

2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 60

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz Chow Hartsell Konski Cancer 2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 61

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemoptysis

bull Fig2 toux

733 689

812 802

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 62

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig3 doul thor 321 279

535 482

Cough

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 63

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 4 overall symptom burden

575 519

648 638

Thoracic pain

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 64

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 5 survie 1a

Cutoff (sensitivity analysis) BED[10] 35Gy vs LD

100 162

555 609

Overall symptom burden

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 65

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cutoff BED[10] 35Gy vs LD

265 217

Overall survival at 1y

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 66

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 7 Tox dysphagie

Cutoff BED[10] 30Gy vs LD

205 149

about x 2

Toxicity (dysphagia)

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 67

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomized trial 250 patients (Falk BMJ 2002)

bull Locally advanced non resectable NSCLC with minimal thoracic symptoms

bull Immediate vs delayed RT (at symptom onset)

bull In delayed arm 56 of patients died without RT

bull No difference in QOL odr OS

bull More acute toxicity in immediate RT arm

Randomized trial (Sundstrom Radiother Oncol 2005)

bull Advanced NSCLC

bull 2 RT schedules (5x4Gy vs 2x85 Gy) immediate RT

bull Stratification according to presenceabsence of thoracic symptoms

bull In asymptomatic patients no long term symptom control but important dysphagia

Timing

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 68

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull in 97 malignant

bull in 5-10 of lung cancer patients

bull Histology (exclude benign disease RT-chemosensible tumours

bull Generally spontanous improvement of symptoms by formation of collaterals

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 69

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Treatment

1 symptomatic

bull steroids

bull diuretics

bull Elevation of headthorax

2 causal bull chemotherapy (SCLC

lymphomas germinal tumours)

bull Endovascular stent placement

bull radiotherapy Palliative care in lung cancer ACCP

evidence- based clinical practice guidelines

(2nd edition)

Kvale Chest 2007

Superior vena cava syndrome

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

Radiotherapy

bull Mostly clinical response within 72 h

bull Complete clinical response at 2 w in 78 of patients with SCLC

and 63 of patients with NSCLC

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duhamel Atlas clinique des maladies

des voies aeacuteriennes Elsevier

wwwupmccancercenterscom

Endobronchial brachytherapy

Cochrane analysis (Cardona The Cochrane

Library 2008)

bull No improved

symptom relief by

addition of

endobronchial

brachytherapy to

EBRT

bull Indicated in selected

patients pretreated

by EBRT with

central

endobronchial

obstruction

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 74

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Ozkok Lung Cancer 2008

Endobronchial brachytherapy

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Take home lung cancer

Dosefractionation

bull Minimum 10x3 Gy 5xw or equivalent

ndash better symptom control and better overall survival

ndash But more toxicity

bull Short schedule for symptom control and limited toxicity

ndashPoor performance status limited life expectancy

Timing

bull RT at the moment of symptom onset

bull No place for bdquoprophylactic palliative RTldquo according to evidence based guidelines

ndashExceptions

bull Young patient good PS aim of local control

bull Imminent symptoms (superior vena cava syndrome central airway obstruction

Rodrigues Pract Rad Oncol 2011

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 80

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Homs Eur J CancerLancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

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Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

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Scoccianti Radiother Oncol 2012

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 100

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SRO Tutorial Palliative Care ndash Palliative Radiotherapy 101

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 102

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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SRO Tutorial Palliative Care ndash Palliative Radiotherapy 35

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Vertebroplastykyphoplasty

bull No prospective data to suggest

that vertkyph obviates the

need for EBRT in painful bone

met

bull Small series of patients treated

by vertkyph plus EBRT

bull Recommendation prospective

trials on patient selection

efficacy toxicity and timing of

vertkyph and RT

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 36

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 37

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Non inferiority study

bull 272 patients randomized

Neuropathic pain

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 38

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 39

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 40

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Spinal cord compression

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 41

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 42

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 43

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Patchell Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 44

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

RT short versus

long course

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 45

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 46

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 47

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 48

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 49

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 50

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull SRO tutorial CNS PD Dr A Pica

bull ScocciantiRicardi Radiother Oncol 2012 Review

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 51

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemorrhage

bull Bleeding in 6-10 of patients with advanced

cancer (Pereira et al Topics in Palliative Care Vol 4 New York

Oxford University Press 2000)

bull haemoptysis

bull haematemesis

bull haematocheziamelaena

bull vaginal bleeding

bull haematuria

bull bleeding in ulcerated skin lesions

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 52

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Mechanisms of haemostatic radiotherapy

bull Sparse literature

bull Coagulation activationsup1

ndash Oxydative endothelial damage

ndash Activation of thrombocytes

ndash Activation of inflammation

bull Long term anti-angiogenetic

sup1 Hallahan et al Oncology (Huntingt) 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 53

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Prostate cancer

bull Reduction of pain and bleeding in hormone refractory

prostate cancer (Kynaston Br J Urol 1990 Kawakami Nippon

Hinyokika Gakkai Zasshi 1993 Kalapurakal Int J Radiat Oncol Biol Phys

2003)

bull 100 improvement in patients with important hematuria (Carlton J Urol 1972)

Bladder cancer (Srinivasan et al Clin Oncol (R Coll Radiol) 1994)

bull 17 Gy in 2 fractions3 days 59 clearance of hematuria

bull 45 Gy in 12 fractions26 days 16 clearance of

hematuria

bull Selection by performance status Palliation (pain and

hematuria) better with hypofractionated RT worse

survival

bull No important side effects

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 54

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung cancer

bull Control of hemoptysis in up to 80 of patients (Brundage

Can J Oncol 1996 Medical Research Council Lung Cancer Working Party

Br J Cancer 1992 Hoskin in Doyle et al Second Edition New York

Oxford University Press 1998 Langendijk Int J Radiat Oncol Biol Phys

2000)

bull Optimal dosefractionation

ndash Hypofractionated RT seems to be equally effective to multiple

fractions (Rees Clin Oncol (R Coll Radiol) 1997 Sundstrom JCO

2004 Phase III Stevens Australas Radiol 1995 Phase III studies of

the MRC (s above)

ndash 10 Gy Single fraction equally effective to multiple fractions less

toxic (Hoskin in Doyle et al Second Edition New York Oxford

University Press 1998 Medical Research Council Lung Cancer

Working Party Br J Cancer 1992)

ndash Mostly total dose of around 20 Gy (multiple fractions) or 8 Gy

single fraction recommended

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 55

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Van Lonkhuijzen

Radiother Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 56

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gynaecologic tumours

bull Cf review van Lonkhuijzen Radiother Oncol 2011

bull Consider intracavitary HDR brachytherapy

Rectal cancer

bull Up to 85 control of rectal bleeding (Hoskin in Doyle et al Second Edition New York Oxford University Press 1998)

Kaposi sarcoma

bull Good palliation for pain bleeding or edema TD 15-40 Gy SD 2 Gy gt90 response 70 complete remission (Review Becker et al Onkologie 2006)

Skin tumours (Miller in Doyle Oxford Textbook of Palliative Medicine New York Oxford University Press 1993)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 57

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duration of treatment effect

Lung cancer

bull Median duration of palliation 50 of remaining life span (30 Gy10d

27 Gy6d 17 Gy2 fract1w apart) (Medical Research Council Br J

Cancer 1991)

bull 1 fract 10 Gy vs 2 fract 85 Gy more patients need repeat RT (Medical Research Council Lung Cancer Working Party Br J Cancer 1992)

bull 417 pat need repeat RT within 3 m after 1x10 Gy (Scolaro Radiol

Med 1995)

Rec ovarian cancer

bull Median duration of palliation 4 m in 90 of patients until death (Corn Cancer 1994)

Cervical endometrial cancer

bull In 50 of patients pall Effect until death with 1-2x10 Gy

ndash Halle IJROBP 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 58

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull RT effective for improvement of

ndashThoracic symptoms (haemoptysis cough thoracic pain

dyspnoea airway obstruction) (Sirzeacuten Acta Oncol 2003 and others)

ndashQOL in about 13 of patients (Langendijk IJROBP 2000)

RT schedules

bull Systematic review (Fairchild JCO 264001-4011 2008)

ndash13 randomized trials 3473 patients

ndashdifferent RT schedules

ndashAim find optimal RT schedule for maximal palliation with

minimal toxicityneed for reirradiation

Thoracic symptoms

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz

Cancer

2007

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz Chow Hartsell Konski Cancer 2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 61

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Haemoptysis

bull Fig2 toux

733 689

812 802

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 62

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig3 doul thor 321 279

535 482

Cough

Fairchild JCO 2008

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 4 overall symptom burden

575 519

648 638

Thoracic pain

Fairchild JCO 2008

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 5 survie 1a

Cutoff (sensitivity analysis) BED[10] 35Gy vs LD

100 162

555 609

Overall symptom burden

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 65

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cutoff BED[10] 35Gy vs LD

265 217

Overall survival at 1y

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 66

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 7 Tox dysphagie

Cutoff BED[10] 30Gy vs LD

205 149

about x 2

Toxicity (dysphagia)

Fairchild JCO 2008

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomized trial 250 patients (Falk BMJ 2002)

bull Locally advanced non resectable NSCLC with minimal thoracic symptoms

bull Immediate vs delayed RT (at symptom onset)

bull In delayed arm 56 of patients died without RT

bull No difference in QOL odr OS

bull More acute toxicity in immediate RT arm

Randomized trial (Sundstrom Radiother Oncol 2005)

bull Advanced NSCLC

bull 2 RT schedules (5x4Gy vs 2x85 Gy) immediate RT

bull Stratification according to presenceabsence of thoracic symptoms

bull In asymptomatic patients no long term symptom control but important dysphagia

Timing

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull in 97 malignant

bull in 5-10 of lung cancer patients

bull Histology (exclude benign disease RT-chemosensible tumours

bull Generally spontanous improvement of symptoms by formation of collaterals

Superior vena cava syndrome

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Treatment

1 symptomatic

bull steroids

bull diuretics

bull Elevation of headthorax

2 causal bull chemotherapy (SCLC

lymphomas germinal tumours)

bull Endovascular stent placement

bull radiotherapy Palliative care in lung cancer ACCP

evidence- based clinical practice guidelines

(2nd edition)

Kvale Chest 2007

Superior vena cava syndrome

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

Radiotherapy

bull Mostly clinical response within 72 h

bull Complete clinical response at 2 w in 78 of patients with SCLC

and 63 of patients with NSCLC

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

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Duhamel Atlas clinique des maladies

des voies aeacuteriennes Elsevier

wwwupmccancercenterscom

Endobronchial brachytherapy

Cochrane analysis (Cardona The Cochrane

Library 2008)

bull No improved

symptom relief by

addition of

endobronchial

brachytherapy to

EBRT

bull Indicated in selected

patients pretreated

by EBRT with

central

endobronchial

obstruction

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Ozkok Lung Cancer 2008

Endobronchial brachytherapy

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Take home lung cancer

Dosefractionation

bull Minimum 10x3 Gy 5xw or equivalent

ndash better symptom control and better overall survival

ndash But more toxicity

bull Short schedule for symptom control and limited toxicity

ndashPoor performance status limited life expectancy

Timing

bull RT at the moment of symptom onset

bull No place for bdquoprophylactic palliative RTldquo according to evidence based guidelines

ndashExceptions

bull Young patient good PS aim of local control

bull Imminent symptoms (superior vena cava syndrome central airway obstruction

Rodrigues Pract Rad Oncol 2011

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Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

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Homs Eur J CancerLancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

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Randomisierte Studien

Homs Lancet 2004

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Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

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Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

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Scoccianti Radiother Oncol 2012

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 37

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bull Non inferiority study

bull 272 patients randomized

Neuropathic pain

Roos Radiother Oncol 2005

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 39

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Spinal cord compression

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 41

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 43

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Patchell Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 44

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

RT short versus

long course

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 45

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 46

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 47

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 48

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 49

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 50

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull SRO tutorial CNS PD Dr A Pica

bull ScocciantiRicardi Radiother Oncol 2012 Review

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 51

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemorrhage

bull Bleeding in 6-10 of patients with advanced

cancer (Pereira et al Topics in Palliative Care Vol 4 New York

Oxford University Press 2000)

bull haemoptysis

bull haematemesis

bull haematocheziamelaena

bull vaginal bleeding

bull haematuria

bull bleeding in ulcerated skin lesions

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 52

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Mechanisms of haemostatic radiotherapy

bull Sparse literature

bull Coagulation activationsup1

ndash Oxydative endothelial damage

ndash Activation of thrombocytes

ndash Activation of inflammation

bull Long term anti-angiogenetic

sup1 Hallahan et al Oncology (Huntingt) 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 53

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Prostate cancer

bull Reduction of pain and bleeding in hormone refractory

prostate cancer (Kynaston Br J Urol 1990 Kawakami Nippon

Hinyokika Gakkai Zasshi 1993 Kalapurakal Int J Radiat Oncol Biol Phys

2003)

bull 100 improvement in patients with important hematuria (Carlton J Urol 1972)

Bladder cancer (Srinivasan et al Clin Oncol (R Coll Radiol) 1994)

bull 17 Gy in 2 fractions3 days 59 clearance of hematuria

bull 45 Gy in 12 fractions26 days 16 clearance of

hematuria

bull Selection by performance status Palliation (pain and

hematuria) better with hypofractionated RT worse

survival

bull No important side effects

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 54

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung cancer

bull Control of hemoptysis in up to 80 of patients (Brundage

Can J Oncol 1996 Medical Research Council Lung Cancer Working Party

Br J Cancer 1992 Hoskin in Doyle et al Second Edition New York

Oxford University Press 1998 Langendijk Int J Radiat Oncol Biol Phys

2000)

bull Optimal dosefractionation

ndash Hypofractionated RT seems to be equally effective to multiple

fractions (Rees Clin Oncol (R Coll Radiol) 1997 Sundstrom JCO

2004 Phase III Stevens Australas Radiol 1995 Phase III studies of

the MRC (s above)

ndash 10 Gy Single fraction equally effective to multiple fractions less

toxic (Hoskin in Doyle et al Second Edition New York Oxford

University Press 1998 Medical Research Council Lung Cancer

Working Party Br J Cancer 1992)

ndash Mostly total dose of around 20 Gy (multiple fractions) or 8 Gy

single fraction recommended

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 55

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Van Lonkhuijzen

Radiother Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 56

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gynaecologic tumours

bull Cf review van Lonkhuijzen Radiother Oncol 2011

bull Consider intracavitary HDR brachytherapy

Rectal cancer

bull Up to 85 control of rectal bleeding (Hoskin in Doyle et al Second Edition New York Oxford University Press 1998)

Kaposi sarcoma

bull Good palliation for pain bleeding or edema TD 15-40 Gy SD 2 Gy gt90 response 70 complete remission (Review Becker et al Onkologie 2006)

Skin tumours (Miller in Doyle Oxford Textbook of Palliative Medicine New York Oxford University Press 1993)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 57

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duration of treatment effect

Lung cancer

bull Median duration of palliation 50 of remaining life span (30 Gy10d

27 Gy6d 17 Gy2 fract1w apart) (Medical Research Council Br J

Cancer 1991)

bull 1 fract 10 Gy vs 2 fract 85 Gy more patients need repeat RT (Medical Research Council Lung Cancer Working Party Br J Cancer 1992)

bull 417 pat need repeat RT within 3 m after 1x10 Gy (Scolaro Radiol

Med 1995)

Rec ovarian cancer

bull Median duration of palliation 4 m in 90 of patients until death (Corn Cancer 1994)

Cervical endometrial cancer

bull In 50 of patients pall Effect until death with 1-2x10 Gy

ndash Halle IJROBP 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 58

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull RT effective for improvement of

ndashThoracic symptoms (haemoptysis cough thoracic pain

dyspnoea airway obstruction) (Sirzeacuten Acta Oncol 2003 and others)

ndashQOL in about 13 of patients (Langendijk IJROBP 2000)

RT schedules

bull Systematic review (Fairchild JCO 264001-4011 2008)

ndash13 randomized trials 3473 patients

ndashdifferent RT schedules

ndashAim find optimal RT schedule for maximal palliation with

minimal toxicityneed for reirradiation

Thoracic symptoms

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 59

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz

Cancer

2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 60

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz Chow Hartsell Konski Cancer 2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 61

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemoptysis

bull Fig2 toux

733 689

812 802

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 62

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig3 doul thor 321 279

535 482

Cough

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 63

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 4 overall symptom burden

575 519

648 638

Thoracic pain

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 64

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 5 survie 1a

Cutoff (sensitivity analysis) BED[10] 35Gy vs LD

100 162

555 609

Overall symptom burden

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 65

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cutoff BED[10] 35Gy vs LD

265 217

Overall survival at 1y

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 66

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 7 Tox dysphagie

Cutoff BED[10] 30Gy vs LD

205 149

about x 2

Toxicity (dysphagia)

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 67

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomized trial 250 patients (Falk BMJ 2002)

bull Locally advanced non resectable NSCLC with minimal thoracic symptoms

bull Immediate vs delayed RT (at symptom onset)

bull In delayed arm 56 of patients died without RT

bull No difference in QOL odr OS

bull More acute toxicity in immediate RT arm

Randomized trial (Sundstrom Radiother Oncol 2005)

bull Advanced NSCLC

bull 2 RT schedules (5x4Gy vs 2x85 Gy) immediate RT

bull Stratification according to presenceabsence of thoracic symptoms

bull In asymptomatic patients no long term symptom control but important dysphagia

Timing

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 68

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull in 97 malignant

bull in 5-10 of lung cancer patients

bull Histology (exclude benign disease RT-chemosensible tumours

bull Generally spontanous improvement of symptoms by formation of collaterals

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 69

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Treatment

1 symptomatic

bull steroids

bull diuretics

bull Elevation of headthorax

2 causal bull chemotherapy (SCLC

lymphomas germinal tumours)

bull Endovascular stent placement

bull radiotherapy Palliative care in lung cancer ACCP

evidence- based clinical practice guidelines

(2nd edition)

Kvale Chest 2007

Superior vena cava syndrome

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

Radiotherapy

bull Mostly clinical response within 72 h

bull Complete clinical response at 2 w in 78 of patients with SCLC

and 63 of patients with NSCLC

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 73

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Duhamel Atlas clinique des maladies

des voies aeacuteriennes Elsevier

wwwupmccancercenterscom

Endobronchial brachytherapy

Cochrane analysis (Cardona The Cochrane

Library 2008)

bull No improved

symptom relief by

addition of

endobronchial

brachytherapy to

EBRT

bull Indicated in selected

patients pretreated

by EBRT with

central

endobronchial

obstruction

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 74

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Ozkok Lung Cancer 2008

Endobronchial brachytherapy

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Take home lung cancer

Dosefractionation

bull Minimum 10x3 Gy 5xw or equivalent

ndash better symptom control and better overall survival

ndash But more toxicity

bull Short schedule for symptom control and limited toxicity

ndashPoor performance status limited life expectancy

Timing

bull RT at the moment of symptom onset

bull No place for bdquoprophylactic palliative RTldquo according to evidence based guidelines

ndashExceptions

bull Young patient good PS aim of local control

bull Imminent symptoms (superior vena cava syndrome central airway obstruction

Rodrigues Pract Rad Oncol 2011

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

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Homs Eur J CancerLancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

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Randomisierte Studien

Homs Lancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

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Scoccianti Radiother Oncol 2012

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Non inferiority study

bull 272 patients randomized

Neuropathic pain

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 38

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 39

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 40

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Spinal cord compression

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 41

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 42

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 43

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Patchell Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 44

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

RT short versus

long course

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 45

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 46

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 47

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 48

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 49

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 50

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull SRO tutorial CNS PD Dr A Pica

bull ScocciantiRicardi Radiother Oncol 2012 Review

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 51

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemorrhage

bull Bleeding in 6-10 of patients with advanced

cancer (Pereira et al Topics in Palliative Care Vol 4 New York

Oxford University Press 2000)

bull haemoptysis

bull haematemesis

bull haematocheziamelaena

bull vaginal bleeding

bull haematuria

bull bleeding in ulcerated skin lesions

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 52

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Mechanisms of haemostatic radiotherapy

bull Sparse literature

bull Coagulation activationsup1

ndash Oxydative endothelial damage

ndash Activation of thrombocytes

ndash Activation of inflammation

bull Long term anti-angiogenetic

sup1 Hallahan et al Oncology (Huntingt) 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 53

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Prostate cancer

bull Reduction of pain and bleeding in hormone refractory

prostate cancer (Kynaston Br J Urol 1990 Kawakami Nippon

Hinyokika Gakkai Zasshi 1993 Kalapurakal Int J Radiat Oncol Biol Phys

2003)

bull 100 improvement in patients with important hematuria (Carlton J Urol 1972)

Bladder cancer (Srinivasan et al Clin Oncol (R Coll Radiol) 1994)

bull 17 Gy in 2 fractions3 days 59 clearance of hematuria

bull 45 Gy in 12 fractions26 days 16 clearance of

hematuria

bull Selection by performance status Palliation (pain and

hematuria) better with hypofractionated RT worse

survival

bull No important side effects

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 54

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung cancer

bull Control of hemoptysis in up to 80 of patients (Brundage

Can J Oncol 1996 Medical Research Council Lung Cancer Working Party

Br J Cancer 1992 Hoskin in Doyle et al Second Edition New York

Oxford University Press 1998 Langendijk Int J Radiat Oncol Biol Phys

2000)

bull Optimal dosefractionation

ndash Hypofractionated RT seems to be equally effective to multiple

fractions (Rees Clin Oncol (R Coll Radiol) 1997 Sundstrom JCO

2004 Phase III Stevens Australas Radiol 1995 Phase III studies of

the MRC (s above)

ndash 10 Gy Single fraction equally effective to multiple fractions less

toxic (Hoskin in Doyle et al Second Edition New York Oxford

University Press 1998 Medical Research Council Lung Cancer

Working Party Br J Cancer 1992)

ndash Mostly total dose of around 20 Gy (multiple fractions) or 8 Gy

single fraction recommended

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 55

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Van Lonkhuijzen

Radiother Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 56

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gynaecologic tumours

bull Cf review van Lonkhuijzen Radiother Oncol 2011

bull Consider intracavitary HDR brachytherapy

Rectal cancer

bull Up to 85 control of rectal bleeding (Hoskin in Doyle et al Second Edition New York Oxford University Press 1998)

Kaposi sarcoma

bull Good palliation for pain bleeding or edema TD 15-40 Gy SD 2 Gy gt90 response 70 complete remission (Review Becker et al Onkologie 2006)

Skin tumours (Miller in Doyle Oxford Textbook of Palliative Medicine New York Oxford University Press 1993)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 57

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duration of treatment effect

Lung cancer

bull Median duration of palliation 50 of remaining life span (30 Gy10d

27 Gy6d 17 Gy2 fract1w apart) (Medical Research Council Br J

Cancer 1991)

bull 1 fract 10 Gy vs 2 fract 85 Gy more patients need repeat RT (Medical Research Council Lung Cancer Working Party Br J Cancer 1992)

bull 417 pat need repeat RT within 3 m after 1x10 Gy (Scolaro Radiol

Med 1995)

Rec ovarian cancer

bull Median duration of palliation 4 m in 90 of patients until death (Corn Cancer 1994)

Cervical endometrial cancer

bull In 50 of patients pall Effect until death with 1-2x10 Gy

ndash Halle IJROBP 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 58

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull RT effective for improvement of

ndashThoracic symptoms (haemoptysis cough thoracic pain

dyspnoea airway obstruction) (Sirzeacuten Acta Oncol 2003 and others)

ndashQOL in about 13 of patients (Langendijk IJROBP 2000)

RT schedules

bull Systematic review (Fairchild JCO 264001-4011 2008)

ndash13 randomized trials 3473 patients

ndashdifferent RT schedules

ndashAim find optimal RT schedule for maximal palliation with

minimal toxicityneed for reirradiation

Thoracic symptoms

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 59

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz

Cancer

2007

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz Chow Hartsell Konski Cancer 2007

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemoptysis

bull Fig2 toux

733 689

812 802

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 62

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig3 doul thor 321 279

535 482

Cough

Fairchild JCO 2008

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 4 overall symptom burden

575 519

648 638

Thoracic pain

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 64

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 5 survie 1a

Cutoff (sensitivity analysis) BED[10] 35Gy vs LD

100 162

555 609

Overall symptom burden

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 65

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cutoff BED[10] 35Gy vs LD

265 217

Overall survival at 1y

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 66

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 7 Tox dysphagie

Cutoff BED[10] 30Gy vs LD

205 149

about x 2

Toxicity (dysphagia)

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 67

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomized trial 250 patients (Falk BMJ 2002)

bull Locally advanced non resectable NSCLC with minimal thoracic symptoms

bull Immediate vs delayed RT (at symptom onset)

bull In delayed arm 56 of patients died without RT

bull No difference in QOL odr OS

bull More acute toxicity in immediate RT arm

Randomized trial (Sundstrom Radiother Oncol 2005)

bull Advanced NSCLC

bull 2 RT schedules (5x4Gy vs 2x85 Gy) immediate RT

bull Stratification according to presenceabsence of thoracic symptoms

bull In asymptomatic patients no long term symptom control but important dysphagia

Timing

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 68

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull in 97 malignant

bull in 5-10 of lung cancer patients

bull Histology (exclude benign disease RT-chemosensible tumours

bull Generally spontanous improvement of symptoms by formation of collaterals

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 69

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Treatment

1 symptomatic

bull steroids

bull diuretics

bull Elevation of headthorax

2 causal bull chemotherapy (SCLC

lymphomas germinal tumours)

bull Endovascular stent placement

bull radiotherapy Palliative care in lung cancer ACCP

evidence- based clinical practice guidelines

(2nd edition)

Kvale Chest 2007

Superior vena cava syndrome

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

Radiotherapy

bull Mostly clinical response within 72 h

bull Complete clinical response at 2 w in 78 of patients with SCLC

and 63 of patients with NSCLC

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duhamel Atlas clinique des maladies

des voies aeacuteriennes Elsevier

wwwupmccancercenterscom

Endobronchial brachytherapy

Cochrane analysis (Cardona The Cochrane

Library 2008)

bull No improved

symptom relief by

addition of

endobronchial

brachytherapy to

EBRT

bull Indicated in selected

patients pretreated

by EBRT with

central

endobronchial

obstruction

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 74

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Ozkok Lung Cancer 2008

Endobronchial brachytherapy

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Take home lung cancer

Dosefractionation

bull Minimum 10x3 Gy 5xw or equivalent

ndash better symptom control and better overall survival

ndash But more toxicity

bull Short schedule for symptom control and limited toxicity

ndashPoor performance status limited life expectancy

Timing

bull RT at the moment of symptom onset

bull No place for bdquoprophylactic palliative RTldquo according to evidence based guidelines

ndashExceptions

bull Young patient good PS aim of local control

bull Imminent symptoms (superior vena cava syndrome central airway obstruction

Rodrigues Pract Rad Oncol 2011

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SRO Tutorial Palliative Care ndash Palliative Radiotherapy 77

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 80

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 82

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

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Scoccianti Radiother Oncol 2012

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 39

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 40

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Spinal cord compression

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 41

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 42

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 43

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Patchell Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 44

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

RT short versus

long course

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 45

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 46

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 47

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 48

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 49

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 50

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull SRO tutorial CNS PD Dr A Pica

bull ScocciantiRicardi Radiother Oncol 2012 Review

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 51

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemorrhage

bull Bleeding in 6-10 of patients with advanced

cancer (Pereira et al Topics in Palliative Care Vol 4 New York

Oxford University Press 2000)

bull haemoptysis

bull haematemesis

bull haematocheziamelaena

bull vaginal bleeding

bull haematuria

bull bleeding in ulcerated skin lesions

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 52

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Mechanisms of haemostatic radiotherapy

bull Sparse literature

bull Coagulation activationsup1

ndash Oxydative endothelial damage

ndash Activation of thrombocytes

ndash Activation of inflammation

bull Long term anti-angiogenetic

sup1 Hallahan et al Oncology (Huntingt) 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 53

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Prostate cancer

bull Reduction of pain and bleeding in hormone refractory

prostate cancer (Kynaston Br J Urol 1990 Kawakami Nippon

Hinyokika Gakkai Zasshi 1993 Kalapurakal Int J Radiat Oncol Biol Phys

2003)

bull 100 improvement in patients with important hematuria (Carlton J Urol 1972)

Bladder cancer (Srinivasan et al Clin Oncol (R Coll Radiol) 1994)

bull 17 Gy in 2 fractions3 days 59 clearance of hematuria

bull 45 Gy in 12 fractions26 days 16 clearance of

hematuria

bull Selection by performance status Palliation (pain and

hematuria) better with hypofractionated RT worse

survival

bull No important side effects

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 54

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung cancer

bull Control of hemoptysis in up to 80 of patients (Brundage

Can J Oncol 1996 Medical Research Council Lung Cancer Working Party

Br J Cancer 1992 Hoskin in Doyle et al Second Edition New York

Oxford University Press 1998 Langendijk Int J Radiat Oncol Biol Phys

2000)

bull Optimal dosefractionation

ndash Hypofractionated RT seems to be equally effective to multiple

fractions (Rees Clin Oncol (R Coll Radiol) 1997 Sundstrom JCO

2004 Phase III Stevens Australas Radiol 1995 Phase III studies of

the MRC (s above)

ndash 10 Gy Single fraction equally effective to multiple fractions less

toxic (Hoskin in Doyle et al Second Edition New York Oxford

University Press 1998 Medical Research Council Lung Cancer

Working Party Br J Cancer 1992)

ndash Mostly total dose of around 20 Gy (multiple fractions) or 8 Gy

single fraction recommended

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 55

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Van Lonkhuijzen

Radiother Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 56

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gynaecologic tumours

bull Cf review van Lonkhuijzen Radiother Oncol 2011

bull Consider intracavitary HDR brachytherapy

Rectal cancer

bull Up to 85 control of rectal bleeding (Hoskin in Doyle et al Second Edition New York Oxford University Press 1998)

Kaposi sarcoma

bull Good palliation for pain bleeding or edema TD 15-40 Gy SD 2 Gy gt90 response 70 complete remission (Review Becker et al Onkologie 2006)

Skin tumours (Miller in Doyle Oxford Textbook of Palliative Medicine New York Oxford University Press 1993)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 57

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duration of treatment effect

Lung cancer

bull Median duration of palliation 50 of remaining life span (30 Gy10d

27 Gy6d 17 Gy2 fract1w apart) (Medical Research Council Br J

Cancer 1991)

bull 1 fract 10 Gy vs 2 fract 85 Gy more patients need repeat RT (Medical Research Council Lung Cancer Working Party Br J Cancer 1992)

bull 417 pat need repeat RT within 3 m after 1x10 Gy (Scolaro Radiol

Med 1995)

Rec ovarian cancer

bull Median duration of palliation 4 m in 90 of patients until death (Corn Cancer 1994)

Cervical endometrial cancer

bull In 50 of patients pall Effect until death with 1-2x10 Gy

ndash Halle IJROBP 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 58

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull RT effective for improvement of

ndashThoracic symptoms (haemoptysis cough thoracic pain

dyspnoea airway obstruction) (Sirzeacuten Acta Oncol 2003 and others)

ndashQOL in about 13 of patients (Langendijk IJROBP 2000)

RT schedules

bull Systematic review (Fairchild JCO 264001-4011 2008)

ndash13 randomized trials 3473 patients

ndashdifferent RT schedules

ndashAim find optimal RT schedule for maximal palliation with

minimal toxicityneed for reirradiation

Thoracic symptoms

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 59

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz

Cancer

2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 60

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz Chow Hartsell Konski Cancer 2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 61

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemoptysis

bull Fig2 toux

733 689

812 802

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 62

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig3 doul thor 321 279

535 482

Cough

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 63

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 4 overall symptom burden

575 519

648 638

Thoracic pain

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 64

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 5 survie 1a

Cutoff (sensitivity analysis) BED[10] 35Gy vs LD

100 162

555 609

Overall symptom burden

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 65

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cutoff BED[10] 35Gy vs LD

265 217

Overall survival at 1y

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 66

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 7 Tox dysphagie

Cutoff BED[10] 30Gy vs LD

205 149

about x 2

Toxicity (dysphagia)

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 67

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomized trial 250 patients (Falk BMJ 2002)

bull Locally advanced non resectable NSCLC with minimal thoracic symptoms

bull Immediate vs delayed RT (at symptom onset)

bull In delayed arm 56 of patients died without RT

bull No difference in QOL odr OS

bull More acute toxicity in immediate RT arm

Randomized trial (Sundstrom Radiother Oncol 2005)

bull Advanced NSCLC

bull 2 RT schedules (5x4Gy vs 2x85 Gy) immediate RT

bull Stratification according to presenceabsence of thoracic symptoms

bull In asymptomatic patients no long term symptom control but important dysphagia

Timing

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 68

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull in 97 malignant

bull in 5-10 of lung cancer patients

bull Histology (exclude benign disease RT-chemosensible tumours

bull Generally spontanous improvement of symptoms by formation of collaterals

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 69

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Treatment

1 symptomatic

bull steroids

bull diuretics

bull Elevation of headthorax

2 causal bull chemotherapy (SCLC

lymphomas germinal tumours)

bull Endovascular stent placement

bull radiotherapy Palliative care in lung cancer ACCP

evidence- based clinical practice guidelines

(2nd edition)

Kvale Chest 2007

Superior vena cava syndrome

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

Radiotherapy

bull Mostly clinical response within 72 h

bull Complete clinical response at 2 w in 78 of patients with SCLC

and 63 of patients with NSCLC

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duhamel Atlas clinique des maladies

des voies aeacuteriennes Elsevier

wwwupmccancercenterscom

Endobronchial brachytherapy

Cochrane analysis (Cardona The Cochrane

Library 2008)

bull No improved

symptom relief by

addition of

endobronchial

brachytherapy to

EBRT

bull Indicated in selected

patients pretreated

by EBRT with

central

endobronchial

obstruction

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 74

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Ozkok Lung Cancer 2008

Endobronchial brachytherapy

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Take home lung cancer

Dosefractionation

bull Minimum 10x3 Gy 5xw or equivalent

ndash better symptom control and better overall survival

ndash But more toxicity

bull Short schedule for symptom control and limited toxicity

ndashPoor performance status limited life expectancy

Timing

bull RT at the moment of symptom onset

bull No place for bdquoprophylactic palliative RTldquo according to evidence based guidelines

ndashExceptions

bull Young patient good PS aim of local control

bull Imminent symptoms (superior vena cava syndrome central airway obstruction

Rodrigues Pract Rad Oncol 2011

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

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Homs Eur J CancerLancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 90

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Scoccianti Radiother Oncol 2012

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SRO Tutorial Palliative Care ndash Palliative Radiotherapy 101

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 102

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Page 39: SRO Tutorial Palliative Care 04.05.2012 Palliative Radiotherapy · 2018-02-22 · SRO Tutorial Palliative Care – Palliative Radiotherapy 30 Jacqueline Vock, Universitätsklinik

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Roos Radiother Oncol 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 40

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Spinal cord compression

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 41

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 42

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lancet 2005

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Patchell Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 44

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

RT short versus

long course

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 45

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 46

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 47

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 48

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 49

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 50

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull SRO tutorial CNS PD Dr A Pica

bull ScocciantiRicardi Radiother Oncol 2012 Review

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 51

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemorrhage

bull Bleeding in 6-10 of patients with advanced

cancer (Pereira et al Topics in Palliative Care Vol 4 New York

Oxford University Press 2000)

bull haemoptysis

bull haematemesis

bull haematocheziamelaena

bull vaginal bleeding

bull haematuria

bull bleeding in ulcerated skin lesions

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 52

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Mechanisms of haemostatic radiotherapy

bull Sparse literature

bull Coagulation activationsup1

ndash Oxydative endothelial damage

ndash Activation of thrombocytes

ndash Activation of inflammation

bull Long term anti-angiogenetic

sup1 Hallahan et al Oncology (Huntingt) 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 53

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Prostate cancer

bull Reduction of pain and bleeding in hormone refractory

prostate cancer (Kynaston Br J Urol 1990 Kawakami Nippon

Hinyokika Gakkai Zasshi 1993 Kalapurakal Int J Radiat Oncol Biol Phys

2003)

bull 100 improvement in patients with important hematuria (Carlton J Urol 1972)

Bladder cancer (Srinivasan et al Clin Oncol (R Coll Radiol) 1994)

bull 17 Gy in 2 fractions3 days 59 clearance of hematuria

bull 45 Gy in 12 fractions26 days 16 clearance of

hematuria

bull Selection by performance status Palliation (pain and

hematuria) better with hypofractionated RT worse

survival

bull No important side effects

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 54

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung cancer

bull Control of hemoptysis in up to 80 of patients (Brundage

Can J Oncol 1996 Medical Research Council Lung Cancer Working Party

Br J Cancer 1992 Hoskin in Doyle et al Second Edition New York

Oxford University Press 1998 Langendijk Int J Radiat Oncol Biol Phys

2000)

bull Optimal dosefractionation

ndash Hypofractionated RT seems to be equally effective to multiple

fractions (Rees Clin Oncol (R Coll Radiol) 1997 Sundstrom JCO

2004 Phase III Stevens Australas Radiol 1995 Phase III studies of

the MRC (s above)

ndash 10 Gy Single fraction equally effective to multiple fractions less

toxic (Hoskin in Doyle et al Second Edition New York Oxford

University Press 1998 Medical Research Council Lung Cancer

Working Party Br J Cancer 1992)

ndash Mostly total dose of around 20 Gy (multiple fractions) or 8 Gy

single fraction recommended

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 55

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Van Lonkhuijzen

Radiother Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 56

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gynaecologic tumours

bull Cf review van Lonkhuijzen Radiother Oncol 2011

bull Consider intracavitary HDR brachytherapy

Rectal cancer

bull Up to 85 control of rectal bleeding (Hoskin in Doyle et al Second Edition New York Oxford University Press 1998)

Kaposi sarcoma

bull Good palliation for pain bleeding or edema TD 15-40 Gy SD 2 Gy gt90 response 70 complete remission (Review Becker et al Onkologie 2006)

Skin tumours (Miller in Doyle Oxford Textbook of Palliative Medicine New York Oxford University Press 1993)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 57

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duration of treatment effect

Lung cancer

bull Median duration of palliation 50 of remaining life span (30 Gy10d

27 Gy6d 17 Gy2 fract1w apart) (Medical Research Council Br J

Cancer 1991)

bull 1 fract 10 Gy vs 2 fract 85 Gy more patients need repeat RT (Medical Research Council Lung Cancer Working Party Br J Cancer 1992)

bull 417 pat need repeat RT within 3 m after 1x10 Gy (Scolaro Radiol

Med 1995)

Rec ovarian cancer

bull Median duration of palliation 4 m in 90 of patients until death (Corn Cancer 1994)

Cervical endometrial cancer

bull In 50 of patients pall Effect until death with 1-2x10 Gy

ndash Halle IJROBP 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 58

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull RT effective for improvement of

ndashThoracic symptoms (haemoptysis cough thoracic pain

dyspnoea airway obstruction) (Sirzeacuten Acta Oncol 2003 and others)

ndashQOL in about 13 of patients (Langendijk IJROBP 2000)

RT schedules

bull Systematic review (Fairchild JCO 264001-4011 2008)

ndash13 randomized trials 3473 patients

ndashdifferent RT schedules

ndashAim find optimal RT schedule for maximal palliation with

minimal toxicityneed for reirradiation

Thoracic symptoms

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 59

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz

Cancer

2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 60

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz Chow Hartsell Konski Cancer 2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 61

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemoptysis

bull Fig2 toux

733 689

812 802

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 62

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig3 doul thor 321 279

535 482

Cough

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 63

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 4 overall symptom burden

575 519

648 638

Thoracic pain

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 64

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 5 survie 1a

Cutoff (sensitivity analysis) BED[10] 35Gy vs LD

100 162

555 609

Overall symptom burden

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 65

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cutoff BED[10] 35Gy vs LD

265 217

Overall survival at 1y

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 66

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 7 Tox dysphagie

Cutoff BED[10] 30Gy vs LD

205 149

about x 2

Toxicity (dysphagia)

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 67

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomized trial 250 patients (Falk BMJ 2002)

bull Locally advanced non resectable NSCLC with minimal thoracic symptoms

bull Immediate vs delayed RT (at symptom onset)

bull In delayed arm 56 of patients died without RT

bull No difference in QOL odr OS

bull More acute toxicity in immediate RT arm

Randomized trial (Sundstrom Radiother Oncol 2005)

bull Advanced NSCLC

bull 2 RT schedules (5x4Gy vs 2x85 Gy) immediate RT

bull Stratification according to presenceabsence of thoracic symptoms

bull In asymptomatic patients no long term symptom control but important dysphagia

Timing

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 68

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull in 97 malignant

bull in 5-10 of lung cancer patients

bull Histology (exclude benign disease RT-chemosensible tumours

bull Generally spontanous improvement of symptoms by formation of collaterals

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 69

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Treatment

1 symptomatic

bull steroids

bull diuretics

bull Elevation of headthorax

2 causal bull chemotherapy (SCLC

lymphomas germinal tumours)

bull Endovascular stent placement

bull radiotherapy Palliative care in lung cancer ACCP

evidence- based clinical practice guidelines

(2nd edition)

Kvale Chest 2007

Superior vena cava syndrome

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

Radiotherapy

bull Mostly clinical response within 72 h

bull Complete clinical response at 2 w in 78 of patients with SCLC

and 63 of patients with NSCLC

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 72

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 73

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duhamel Atlas clinique des maladies

des voies aeacuteriennes Elsevier

wwwupmccancercenterscom

Endobronchial brachytherapy

Cochrane analysis (Cardona The Cochrane

Library 2008)

bull No improved

symptom relief by

addition of

endobronchial

brachytherapy to

EBRT

bull Indicated in selected

patients pretreated

by EBRT with

central

endobronchial

obstruction

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 74

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Ozkok Lung Cancer 2008

Endobronchial brachytherapy

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Take home lung cancer

Dosefractionation

bull Minimum 10x3 Gy 5xw or equivalent

ndash better symptom control and better overall survival

ndash But more toxicity

bull Short schedule for symptom control and limited toxicity

ndashPoor performance status limited life expectancy

Timing

bull RT at the moment of symptom onset

bull No place for bdquoprophylactic palliative RTldquo according to evidence based guidelines

ndashExceptions

bull Young patient good PS aim of local control

bull Imminent symptoms (superior vena cava syndrome central airway obstruction

Rodrigues Pract Rad Oncol 2011

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 77

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 78

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 80

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 82

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 83

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 90

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

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Scoccianti Radiother Oncol 2012

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Page 40: SRO Tutorial Palliative Care 04.05.2012 Palliative Radiotherapy · 2018-02-22 · SRO Tutorial Palliative Care – Palliative Radiotherapy 30 Jacqueline Vock, Universitätsklinik

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Spinal cord compression

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 41

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 42

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 43

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Patchell Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 44

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

RT short versus

long course

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 45

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 46

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 47

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 48

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 49

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 50

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull SRO tutorial CNS PD Dr A Pica

bull ScocciantiRicardi Radiother Oncol 2012 Review

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 51

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemorrhage

bull Bleeding in 6-10 of patients with advanced

cancer (Pereira et al Topics in Palliative Care Vol 4 New York

Oxford University Press 2000)

bull haemoptysis

bull haematemesis

bull haematocheziamelaena

bull vaginal bleeding

bull haematuria

bull bleeding in ulcerated skin lesions

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 52

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Mechanisms of haemostatic radiotherapy

bull Sparse literature

bull Coagulation activationsup1

ndash Oxydative endothelial damage

ndash Activation of thrombocytes

ndash Activation of inflammation

bull Long term anti-angiogenetic

sup1 Hallahan et al Oncology (Huntingt) 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 53

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Prostate cancer

bull Reduction of pain and bleeding in hormone refractory

prostate cancer (Kynaston Br J Urol 1990 Kawakami Nippon

Hinyokika Gakkai Zasshi 1993 Kalapurakal Int J Radiat Oncol Biol Phys

2003)

bull 100 improvement in patients with important hematuria (Carlton J Urol 1972)

Bladder cancer (Srinivasan et al Clin Oncol (R Coll Radiol) 1994)

bull 17 Gy in 2 fractions3 days 59 clearance of hematuria

bull 45 Gy in 12 fractions26 days 16 clearance of

hematuria

bull Selection by performance status Palliation (pain and

hematuria) better with hypofractionated RT worse

survival

bull No important side effects

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 54

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung cancer

bull Control of hemoptysis in up to 80 of patients (Brundage

Can J Oncol 1996 Medical Research Council Lung Cancer Working Party

Br J Cancer 1992 Hoskin in Doyle et al Second Edition New York

Oxford University Press 1998 Langendijk Int J Radiat Oncol Biol Phys

2000)

bull Optimal dosefractionation

ndash Hypofractionated RT seems to be equally effective to multiple

fractions (Rees Clin Oncol (R Coll Radiol) 1997 Sundstrom JCO

2004 Phase III Stevens Australas Radiol 1995 Phase III studies of

the MRC (s above)

ndash 10 Gy Single fraction equally effective to multiple fractions less

toxic (Hoskin in Doyle et al Second Edition New York Oxford

University Press 1998 Medical Research Council Lung Cancer

Working Party Br J Cancer 1992)

ndash Mostly total dose of around 20 Gy (multiple fractions) or 8 Gy

single fraction recommended

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 55

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Van Lonkhuijzen

Radiother Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 56

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gynaecologic tumours

bull Cf review van Lonkhuijzen Radiother Oncol 2011

bull Consider intracavitary HDR brachytherapy

Rectal cancer

bull Up to 85 control of rectal bleeding (Hoskin in Doyle et al Second Edition New York Oxford University Press 1998)

Kaposi sarcoma

bull Good palliation for pain bleeding or edema TD 15-40 Gy SD 2 Gy gt90 response 70 complete remission (Review Becker et al Onkologie 2006)

Skin tumours (Miller in Doyle Oxford Textbook of Palliative Medicine New York Oxford University Press 1993)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 57

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duration of treatment effect

Lung cancer

bull Median duration of palliation 50 of remaining life span (30 Gy10d

27 Gy6d 17 Gy2 fract1w apart) (Medical Research Council Br J

Cancer 1991)

bull 1 fract 10 Gy vs 2 fract 85 Gy more patients need repeat RT (Medical Research Council Lung Cancer Working Party Br J Cancer 1992)

bull 417 pat need repeat RT within 3 m after 1x10 Gy (Scolaro Radiol

Med 1995)

Rec ovarian cancer

bull Median duration of palliation 4 m in 90 of patients until death (Corn Cancer 1994)

Cervical endometrial cancer

bull In 50 of patients pall Effect until death with 1-2x10 Gy

ndash Halle IJROBP 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 58

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull RT effective for improvement of

ndashThoracic symptoms (haemoptysis cough thoracic pain

dyspnoea airway obstruction) (Sirzeacuten Acta Oncol 2003 and others)

ndashQOL in about 13 of patients (Langendijk IJROBP 2000)

RT schedules

bull Systematic review (Fairchild JCO 264001-4011 2008)

ndash13 randomized trials 3473 patients

ndashdifferent RT schedules

ndashAim find optimal RT schedule for maximal palliation with

minimal toxicityneed for reirradiation

Thoracic symptoms

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 59

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz

Cancer

2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 60

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz Chow Hartsell Konski Cancer 2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 61

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemoptysis

bull Fig2 toux

733 689

812 802

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 62

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig3 doul thor 321 279

535 482

Cough

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 63

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 4 overall symptom burden

575 519

648 638

Thoracic pain

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 64

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 5 survie 1a

Cutoff (sensitivity analysis) BED[10] 35Gy vs LD

100 162

555 609

Overall symptom burden

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 65

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cutoff BED[10] 35Gy vs LD

265 217

Overall survival at 1y

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 66

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 7 Tox dysphagie

Cutoff BED[10] 30Gy vs LD

205 149

about x 2

Toxicity (dysphagia)

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 67

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomized trial 250 patients (Falk BMJ 2002)

bull Locally advanced non resectable NSCLC with minimal thoracic symptoms

bull Immediate vs delayed RT (at symptom onset)

bull In delayed arm 56 of patients died without RT

bull No difference in QOL odr OS

bull More acute toxicity in immediate RT arm

Randomized trial (Sundstrom Radiother Oncol 2005)

bull Advanced NSCLC

bull 2 RT schedules (5x4Gy vs 2x85 Gy) immediate RT

bull Stratification according to presenceabsence of thoracic symptoms

bull In asymptomatic patients no long term symptom control but important dysphagia

Timing

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 68

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull in 97 malignant

bull in 5-10 of lung cancer patients

bull Histology (exclude benign disease RT-chemosensible tumours

bull Generally spontanous improvement of symptoms by formation of collaterals

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 69

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Treatment

1 symptomatic

bull steroids

bull diuretics

bull Elevation of headthorax

2 causal bull chemotherapy (SCLC

lymphomas germinal tumours)

bull Endovascular stent placement

bull radiotherapy Palliative care in lung cancer ACCP

evidence- based clinical practice guidelines

(2nd edition)

Kvale Chest 2007

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 70

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

Radiotherapy

bull Mostly clinical response within 72 h

bull Complete clinical response at 2 w in 78 of patients with SCLC

and 63 of patients with NSCLC

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 71

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 72

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 73

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duhamel Atlas clinique des maladies

des voies aeacuteriennes Elsevier

wwwupmccancercenterscom

Endobronchial brachytherapy

Cochrane analysis (Cardona The Cochrane

Library 2008)

bull No improved

symptom relief by

addition of

endobronchial

brachytherapy to

EBRT

bull Indicated in selected

patients pretreated

by EBRT with

central

endobronchial

obstruction

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 74

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Ozkok Lung Cancer 2008

Endobronchial brachytherapy

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 75

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Take home lung cancer

Dosefractionation

bull Minimum 10x3 Gy 5xw or equivalent

ndash better symptom control and better overall survival

ndash But more toxicity

bull Short schedule for symptom control and limited toxicity

ndashPoor performance status limited life expectancy

Timing

bull RT at the moment of symptom onset

bull No place for bdquoprophylactic palliative RTldquo according to evidence based guidelines

ndashExceptions

bull Young patient good PS aim of local control

bull Imminent symptoms (superior vena cava syndrome central airway obstruction

Rodrigues Pract Rad Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 76

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Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

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Homs Eur J CancerLancet 2004

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ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

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Randomisierte Studien

Homs Lancet 2004

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Randomisierte Studien

Homs Lancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

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Scoccianti Radiother Oncol 2012

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 42

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lancet 2005

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Patchell Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 44

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

RT short versus

long course

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Maranzano Radiother Oncol 2009

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 48

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 50

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull SRO tutorial CNS PD Dr A Pica

bull ScocciantiRicardi Radiother Oncol 2012 Review

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 51

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemorrhage

bull Bleeding in 6-10 of patients with advanced

cancer (Pereira et al Topics in Palliative Care Vol 4 New York

Oxford University Press 2000)

bull haemoptysis

bull haematemesis

bull haematocheziamelaena

bull vaginal bleeding

bull haematuria

bull bleeding in ulcerated skin lesions

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 52

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Mechanisms of haemostatic radiotherapy

bull Sparse literature

bull Coagulation activationsup1

ndash Oxydative endothelial damage

ndash Activation of thrombocytes

ndash Activation of inflammation

bull Long term anti-angiogenetic

sup1 Hallahan et al Oncology (Huntingt) 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 53

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Prostate cancer

bull Reduction of pain and bleeding in hormone refractory

prostate cancer (Kynaston Br J Urol 1990 Kawakami Nippon

Hinyokika Gakkai Zasshi 1993 Kalapurakal Int J Radiat Oncol Biol Phys

2003)

bull 100 improvement in patients with important hematuria (Carlton J Urol 1972)

Bladder cancer (Srinivasan et al Clin Oncol (R Coll Radiol) 1994)

bull 17 Gy in 2 fractions3 days 59 clearance of hematuria

bull 45 Gy in 12 fractions26 days 16 clearance of

hematuria

bull Selection by performance status Palliation (pain and

hematuria) better with hypofractionated RT worse

survival

bull No important side effects

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 54

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung cancer

bull Control of hemoptysis in up to 80 of patients (Brundage

Can J Oncol 1996 Medical Research Council Lung Cancer Working Party

Br J Cancer 1992 Hoskin in Doyle et al Second Edition New York

Oxford University Press 1998 Langendijk Int J Radiat Oncol Biol Phys

2000)

bull Optimal dosefractionation

ndash Hypofractionated RT seems to be equally effective to multiple

fractions (Rees Clin Oncol (R Coll Radiol) 1997 Sundstrom JCO

2004 Phase III Stevens Australas Radiol 1995 Phase III studies of

the MRC (s above)

ndash 10 Gy Single fraction equally effective to multiple fractions less

toxic (Hoskin in Doyle et al Second Edition New York Oxford

University Press 1998 Medical Research Council Lung Cancer

Working Party Br J Cancer 1992)

ndash Mostly total dose of around 20 Gy (multiple fractions) or 8 Gy

single fraction recommended

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 55

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Van Lonkhuijzen

Radiother Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 56

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gynaecologic tumours

bull Cf review van Lonkhuijzen Radiother Oncol 2011

bull Consider intracavitary HDR brachytherapy

Rectal cancer

bull Up to 85 control of rectal bleeding (Hoskin in Doyle et al Second Edition New York Oxford University Press 1998)

Kaposi sarcoma

bull Good palliation for pain bleeding or edema TD 15-40 Gy SD 2 Gy gt90 response 70 complete remission (Review Becker et al Onkologie 2006)

Skin tumours (Miller in Doyle Oxford Textbook of Palliative Medicine New York Oxford University Press 1993)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 57

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duration of treatment effect

Lung cancer

bull Median duration of palliation 50 of remaining life span (30 Gy10d

27 Gy6d 17 Gy2 fract1w apart) (Medical Research Council Br J

Cancer 1991)

bull 1 fract 10 Gy vs 2 fract 85 Gy more patients need repeat RT (Medical Research Council Lung Cancer Working Party Br J Cancer 1992)

bull 417 pat need repeat RT within 3 m after 1x10 Gy (Scolaro Radiol

Med 1995)

Rec ovarian cancer

bull Median duration of palliation 4 m in 90 of patients until death (Corn Cancer 1994)

Cervical endometrial cancer

bull In 50 of patients pall Effect until death with 1-2x10 Gy

ndash Halle IJROBP 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 58

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull RT effective for improvement of

ndashThoracic symptoms (haemoptysis cough thoracic pain

dyspnoea airway obstruction) (Sirzeacuten Acta Oncol 2003 and others)

ndashQOL in about 13 of patients (Langendijk IJROBP 2000)

RT schedules

bull Systematic review (Fairchild JCO 264001-4011 2008)

ndash13 randomized trials 3473 patients

ndashdifferent RT schedules

ndashAim find optimal RT schedule for maximal palliation with

minimal toxicityneed for reirradiation

Thoracic symptoms

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 59

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz

Cancer

2007

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz Chow Hartsell Konski Cancer 2007

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemoptysis

bull Fig2 toux

733 689

812 802

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 62

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig3 doul thor 321 279

535 482

Cough

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 63

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 4 overall symptom burden

575 519

648 638

Thoracic pain

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 64

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 5 survie 1a

Cutoff (sensitivity analysis) BED[10] 35Gy vs LD

100 162

555 609

Overall symptom burden

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 65

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cutoff BED[10] 35Gy vs LD

265 217

Overall survival at 1y

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 66

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 7 Tox dysphagie

Cutoff BED[10] 30Gy vs LD

205 149

about x 2

Toxicity (dysphagia)

Fairchild JCO 2008

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomized trial 250 patients (Falk BMJ 2002)

bull Locally advanced non resectable NSCLC with minimal thoracic symptoms

bull Immediate vs delayed RT (at symptom onset)

bull In delayed arm 56 of patients died without RT

bull No difference in QOL odr OS

bull More acute toxicity in immediate RT arm

Randomized trial (Sundstrom Radiother Oncol 2005)

bull Advanced NSCLC

bull 2 RT schedules (5x4Gy vs 2x85 Gy) immediate RT

bull Stratification according to presenceabsence of thoracic symptoms

bull In asymptomatic patients no long term symptom control but important dysphagia

Timing

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 68

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull in 97 malignant

bull in 5-10 of lung cancer patients

bull Histology (exclude benign disease RT-chemosensible tumours

bull Generally spontanous improvement of symptoms by formation of collaterals

Superior vena cava syndrome

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Treatment

1 symptomatic

bull steroids

bull diuretics

bull Elevation of headthorax

2 causal bull chemotherapy (SCLC

lymphomas germinal tumours)

bull Endovascular stent placement

bull radiotherapy Palliative care in lung cancer ACCP

evidence- based clinical practice guidelines

(2nd edition)

Kvale Chest 2007

Superior vena cava syndrome

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

Radiotherapy

bull Mostly clinical response within 72 h

bull Complete clinical response at 2 w in 78 of patients with SCLC

and 63 of patients with NSCLC

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

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Duhamel Atlas clinique des maladies

des voies aeacuteriennes Elsevier

wwwupmccancercenterscom

Endobronchial brachytherapy

Cochrane analysis (Cardona The Cochrane

Library 2008)

bull No improved

symptom relief by

addition of

endobronchial

brachytherapy to

EBRT

bull Indicated in selected

patients pretreated

by EBRT with

central

endobronchial

obstruction

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 74

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Ozkok Lung Cancer 2008

Endobronchial brachytherapy

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Take home lung cancer

Dosefractionation

bull Minimum 10x3 Gy 5xw or equivalent

ndash better symptom control and better overall survival

ndash But more toxicity

bull Short schedule for symptom control and limited toxicity

ndashPoor performance status limited life expectancy

Timing

bull RT at the moment of symptom onset

bull No place for bdquoprophylactic palliative RTldquo according to evidence based guidelines

ndashExceptions

bull Young patient good PS aim of local control

bull Imminent symptoms (superior vena cava syndrome central airway obstruction

Rodrigues Pract Rad Oncol 2011

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

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Homs Eur J CancerLancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 85

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 90

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 98

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 99

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Scoccianti Radiother Oncol 2012

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 43

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Patchell Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 44

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

RT short versus

long course

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 45

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 46

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 47

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 48

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 49

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 50

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull SRO tutorial CNS PD Dr A Pica

bull ScocciantiRicardi Radiother Oncol 2012 Review

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 51

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemorrhage

bull Bleeding in 6-10 of patients with advanced

cancer (Pereira et al Topics in Palliative Care Vol 4 New York

Oxford University Press 2000)

bull haemoptysis

bull haematemesis

bull haematocheziamelaena

bull vaginal bleeding

bull haematuria

bull bleeding in ulcerated skin lesions

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 52

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Mechanisms of haemostatic radiotherapy

bull Sparse literature

bull Coagulation activationsup1

ndash Oxydative endothelial damage

ndash Activation of thrombocytes

ndash Activation of inflammation

bull Long term anti-angiogenetic

sup1 Hallahan et al Oncology (Huntingt) 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 53

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Prostate cancer

bull Reduction of pain and bleeding in hormone refractory

prostate cancer (Kynaston Br J Urol 1990 Kawakami Nippon

Hinyokika Gakkai Zasshi 1993 Kalapurakal Int J Radiat Oncol Biol Phys

2003)

bull 100 improvement in patients with important hematuria (Carlton J Urol 1972)

Bladder cancer (Srinivasan et al Clin Oncol (R Coll Radiol) 1994)

bull 17 Gy in 2 fractions3 days 59 clearance of hematuria

bull 45 Gy in 12 fractions26 days 16 clearance of

hematuria

bull Selection by performance status Palliation (pain and

hematuria) better with hypofractionated RT worse

survival

bull No important side effects

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 54

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung cancer

bull Control of hemoptysis in up to 80 of patients (Brundage

Can J Oncol 1996 Medical Research Council Lung Cancer Working Party

Br J Cancer 1992 Hoskin in Doyle et al Second Edition New York

Oxford University Press 1998 Langendijk Int J Radiat Oncol Biol Phys

2000)

bull Optimal dosefractionation

ndash Hypofractionated RT seems to be equally effective to multiple

fractions (Rees Clin Oncol (R Coll Radiol) 1997 Sundstrom JCO

2004 Phase III Stevens Australas Radiol 1995 Phase III studies of

the MRC (s above)

ndash 10 Gy Single fraction equally effective to multiple fractions less

toxic (Hoskin in Doyle et al Second Edition New York Oxford

University Press 1998 Medical Research Council Lung Cancer

Working Party Br J Cancer 1992)

ndash Mostly total dose of around 20 Gy (multiple fractions) or 8 Gy

single fraction recommended

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 55

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Van Lonkhuijzen

Radiother Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 56

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gynaecologic tumours

bull Cf review van Lonkhuijzen Radiother Oncol 2011

bull Consider intracavitary HDR brachytherapy

Rectal cancer

bull Up to 85 control of rectal bleeding (Hoskin in Doyle et al Second Edition New York Oxford University Press 1998)

Kaposi sarcoma

bull Good palliation for pain bleeding or edema TD 15-40 Gy SD 2 Gy gt90 response 70 complete remission (Review Becker et al Onkologie 2006)

Skin tumours (Miller in Doyle Oxford Textbook of Palliative Medicine New York Oxford University Press 1993)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 57

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duration of treatment effect

Lung cancer

bull Median duration of palliation 50 of remaining life span (30 Gy10d

27 Gy6d 17 Gy2 fract1w apart) (Medical Research Council Br J

Cancer 1991)

bull 1 fract 10 Gy vs 2 fract 85 Gy more patients need repeat RT (Medical Research Council Lung Cancer Working Party Br J Cancer 1992)

bull 417 pat need repeat RT within 3 m after 1x10 Gy (Scolaro Radiol

Med 1995)

Rec ovarian cancer

bull Median duration of palliation 4 m in 90 of patients until death (Corn Cancer 1994)

Cervical endometrial cancer

bull In 50 of patients pall Effect until death with 1-2x10 Gy

ndash Halle IJROBP 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 58

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull RT effective for improvement of

ndashThoracic symptoms (haemoptysis cough thoracic pain

dyspnoea airway obstruction) (Sirzeacuten Acta Oncol 2003 and others)

ndashQOL in about 13 of patients (Langendijk IJROBP 2000)

RT schedules

bull Systematic review (Fairchild JCO 264001-4011 2008)

ndash13 randomized trials 3473 patients

ndashdifferent RT schedules

ndashAim find optimal RT schedule for maximal palliation with

minimal toxicityneed for reirradiation

Thoracic symptoms

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 59

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz

Cancer

2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 60

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz Chow Hartsell Konski Cancer 2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 61

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemoptysis

bull Fig2 toux

733 689

812 802

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 62

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig3 doul thor 321 279

535 482

Cough

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 63

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 4 overall symptom burden

575 519

648 638

Thoracic pain

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 64

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 5 survie 1a

Cutoff (sensitivity analysis) BED[10] 35Gy vs LD

100 162

555 609

Overall symptom burden

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 65

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cutoff BED[10] 35Gy vs LD

265 217

Overall survival at 1y

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 66

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 7 Tox dysphagie

Cutoff BED[10] 30Gy vs LD

205 149

about x 2

Toxicity (dysphagia)

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 67

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomized trial 250 patients (Falk BMJ 2002)

bull Locally advanced non resectable NSCLC with minimal thoracic symptoms

bull Immediate vs delayed RT (at symptom onset)

bull In delayed arm 56 of patients died without RT

bull No difference in QOL odr OS

bull More acute toxicity in immediate RT arm

Randomized trial (Sundstrom Radiother Oncol 2005)

bull Advanced NSCLC

bull 2 RT schedules (5x4Gy vs 2x85 Gy) immediate RT

bull Stratification according to presenceabsence of thoracic symptoms

bull In asymptomatic patients no long term symptom control but important dysphagia

Timing

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 68

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull in 97 malignant

bull in 5-10 of lung cancer patients

bull Histology (exclude benign disease RT-chemosensible tumours

bull Generally spontanous improvement of symptoms by formation of collaterals

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 69

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Treatment

1 symptomatic

bull steroids

bull diuretics

bull Elevation of headthorax

2 causal bull chemotherapy (SCLC

lymphomas germinal tumours)

bull Endovascular stent placement

bull radiotherapy Palliative care in lung cancer ACCP

evidence- based clinical practice guidelines

(2nd edition)

Kvale Chest 2007

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 70

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

Radiotherapy

bull Mostly clinical response within 72 h

bull Complete clinical response at 2 w in 78 of patients with SCLC

and 63 of patients with NSCLC

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 72

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duhamel Atlas clinique des maladies

des voies aeacuteriennes Elsevier

wwwupmccancercenterscom

Endobronchial brachytherapy

Cochrane analysis (Cardona The Cochrane

Library 2008)

bull No improved

symptom relief by

addition of

endobronchial

brachytherapy to

EBRT

bull Indicated in selected

patients pretreated

by EBRT with

central

endobronchial

obstruction

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 74

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Ozkok Lung Cancer 2008

Endobronchial brachytherapy

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Take home lung cancer

Dosefractionation

bull Minimum 10x3 Gy 5xw or equivalent

ndash better symptom control and better overall survival

ndash But more toxicity

bull Short schedule for symptom control and limited toxicity

ndashPoor performance status limited life expectancy

Timing

bull RT at the moment of symptom onset

bull No place for bdquoprophylactic palliative RTldquo according to evidence based guidelines

ndashExceptions

bull Young patient good PS aim of local control

bull Imminent symptoms (superior vena cava syndrome central airway obstruction

Rodrigues Pract Rad Oncol 2011

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 80

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 82

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 83

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 84

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 85

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 90

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 98

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 99

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Scoccianti Radiother Oncol 2012

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Patchell Lancet 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 44

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

RT short versus

long course

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 45

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 46

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 47

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 48

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 49

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 50

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull SRO tutorial CNS PD Dr A Pica

bull ScocciantiRicardi Radiother Oncol 2012 Review

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 51

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemorrhage

bull Bleeding in 6-10 of patients with advanced

cancer (Pereira et al Topics in Palliative Care Vol 4 New York

Oxford University Press 2000)

bull haemoptysis

bull haematemesis

bull haematocheziamelaena

bull vaginal bleeding

bull haematuria

bull bleeding in ulcerated skin lesions

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 52

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Mechanisms of haemostatic radiotherapy

bull Sparse literature

bull Coagulation activationsup1

ndash Oxydative endothelial damage

ndash Activation of thrombocytes

ndash Activation of inflammation

bull Long term anti-angiogenetic

sup1 Hallahan et al Oncology (Huntingt) 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 53

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Prostate cancer

bull Reduction of pain and bleeding in hormone refractory

prostate cancer (Kynaston Br J Urol 1990 Kawakami Nippon

Hinyokika Gakkai Zasshi 1993 Kalapurakal Int J Radiat Oncol Biol Phys

2003)

bull 100 improvement in patients with important hematuria (Carlton J Urol 1972)

Bladder cancer (Srinivasan et al Clin Oncol (R Coll Radiol) 1994)

bull 17 Gy in 2 fractions3 days 59 clearance of hematuria

bull 45 Gy in 12 fractions26 days 16 clearance of

hematuria

bull Selection by performance status Palliation (pain and

hematuria) better with hypofractionated RT worse

survival

bull No important side effects

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 54

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung cancer

bull Control of hemoptysis in up to 80 of patients (Brundage

Can J Oncol 1996 Medical Research Council Lung Cancer Working Party

Br J Cancer 1992 Hoskin in Doyle et al Second Edition New York

Oxford University Press 1998 Langendijk Int J Radiat Oncol Biol Phys

2000)

bull Optimal dosefractionation

ndash Hypofractionated RT seems to be equally effective to multiple

fractions (Rees Clin Oncol (R Coll Radiol) 1997 Sundstrom JCO

2004 Phase III Stevens Australas Radiol 1995 Phase III studies of

the MRC (s above)

ndash 10 Gy Single fraction equally effective to multiple fractions less

toxic (Hoskin in Doyle et al Second Edition New York Oxford

University Press 1998 Medical Research Council Lung Cancer

Working Party Br J Cancer 1992)

ndash Mostly total dose of around 20 Gy (multiple fractions) or 8 Gy

single fraction recommended

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 55

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Van Lonkhuijzen

Radiother Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 56

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gynaecologic tumours

bull Cf review van Lonkhuijzen Radiother Oncol 2011

bull Consider intracavitary HDR brachytherapy

Rectal cancer

bull Up to 85 control of rectal bleeding (Hoskin in Doyle et al Second Edition New York Oxford University Press 1998)

Kaposi sarcoma

bull Good palliation for pain bleeding or edema TD 15-40 Gy SD 2 Gy gt90 response 70 complete remission (Review Becker et al Onkologie 2006)

Skin tumours (Miller in Doyle Oxford Textbook of Palliative Medicine New York Oxford University Press 1993)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 57

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duration of treatment effect

Lung cancer

bull Median duration of palliation 50 of remaining life span (30 Gy10d

27 Gy6d 17 Gy2 fract1w apart) (Medical Research Council Br J

Cancer 1991)

bull 1 fract 10 Gy vs 2 fract 85 Gy more patients need repeat RT (Medical Research Council Lung Cancer Working Party Br J Cancer 1992)

bull 417 pat need repeat RT within 3 m after 1x10 Gy (Scolaro Radiol

Med 1995)

Rec ovarian cancer

bull Median duration of palliation 4 m in 90 of patients until death (Corn Cancer 1994)

Cervical endometrial cancer

bull In 50 of patients pall Effect until death with 1-2x10 Gy

ndash Halle IJROBP 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 58

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull RT effective for improvement of

ndashThoracic symptoms (haemoptysis cough thoracic pain

dyspnoea airway obstruction) (Sirzeacuten Acta Oncol 2003 and others)

ndashQOL in about 13 of patients (Langendijk IJROBP 2000)

RT schedules

bull Systematic review (Fairchild JCO 264001-4011 2008)

ndash13 randomized trials 3473 patients

ndashdifferent RT schedules

ndashAim find optimal RT schedule for maximal palliation with

minimal toxicityneed for reirradiation

Thoracic symptoms

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 59

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz

Cancer

2007

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz Chow Hartsell Konski Cancer 2007

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemoptysis

bull Fig2 toux

733 689

812 802

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 62

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig3 doul thor 321 279

535 482

Cough

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 63

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 4 overall symptom burden

575 519

648 638

Thoracic pain

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 64

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 5 survie 1a

Cutoff (sensitivity analysis) BED[10] 35Gy vs LD

100 162

555 609

Overall symptom burden

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 65

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cutoff BED[10] 35Gy vs LD

265 217

Overall survival at 1y

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 66

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 7 Tox dysphagie

Cutoff BED[10] 30Gy vs LD

205 149

about x 2

Toxicity (dysphagia)

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 67

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomized trial 250 patients (Falk BMJ 2002)

bull Locally advanced non resectable NSCLC with minimal thoracic symptoms

bull Immediate vs delayed RT (at symptom onset)

bull In delayed arm 56 of patients died without RT

bull No difference in QOL odr OS

bull More acute toxicity in immediate RT arm

Randomized trial (Sundstrom Radiother Oncol 2005)

bull Advanced NSCLC

bull 2 RT schedules (5x4Gy vs 2x85 Gy) immediate RT

bull Stratification according to presenceabsence of thoracic symptoms

bull In asymptomatic patients no long term symptom control but important dysphagia

Timing

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 68

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull in 97 malignant

bull in 5-10 of lung cancer patients

bull Histology (exclude benign disease RT-chemosensible tumours

bull Generally spontanous improvement of symptoms by formation of collaterals

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 69

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Treatment

1 symptomatic

bull steroids

bull diuretics

bull Elevation of headthorax

2 causal bull chemotherapy (SCLC

lymphomas germinal tumours)

bull Endovascular stent placement

bull radiotherapy Palliative care in lung cancer ACCP

evidence- based clinical practice guidelines

(2nd edition)

Kvale Chest 2007

Superior vena cava syndrome

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

Radiotherapy

bull Mostly clinical response within 72 h

bull Complete clinical response at 2 w in 78 of patients with SCLC

and 63 of patients with NSCLC

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 72

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duhamel Atlas clinique des maladies

des voies aeacuteriennes Elsevier

wwwupmccancercenterscom

Endobronchial brachytherapy

Cochrane analysis (Cardona The Cochrane

Library 2008)

bull No improved

symptom relief by

addition of

endobronchial

brachytherapy to

EBRT

bull Indicated in selected

patients pretreated

by EBRT with

central

endobronchial

obstruction

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 74

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Ozkok Lung Cancer 2008

Endobronchial brachytherapy

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Take home lung cancer

Dosefractionation

bull Minimum 10x3 Gy 5xw or equivalent

ndash better symptom control and better overall survival

ndash But more toxicity

bull Short schedule for symptom control and limited toxicity

ndashPoor performance status limited life expectancy

Timing

bull RT at the moment of symptom onset

bull No place for bdquoprophylactic palliative RTldquo according to evidence based guidelines

ndashExceptions

bull Young patient good PS aim of local control

bull Imminent symptoms (superior vena cava syndrome central airway obstruction

Rodrigues Pract Rad Oncol 2011

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 77

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 80

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 82

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 83

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 84

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 85

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 90

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 98

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 99

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Scoccianti Radiother Oncol 2012

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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SRO Tutorial Palliative Care ndash Palliative Radiotherapy 44

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

RT short versus

long course

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 45

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 46

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 47

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 48

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 49

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 50

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull SRO tutorial CNS PD Dr A Pica

bull ScocciantiRicardi Radiother Oncol 2012 Review

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 51

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemorrhage

bull Bleeding in 6-10 of patients with advanced

cancer (Pereira et al Topics in Palliative Care Vol 4 New York

Oxford University Press 2000)

bull haemoptysis

bull haematemesis

bull haematocheziamelaena

bull vaginal bleeding

bull haematuria

bull bleeding in ulcerated skin lesions

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 52

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Mechanisms of haemostatic radiotherapy

bull Sparse literature

bull Coagulation activationsup1

ndash Oxydative endothelial damage

ndash Activation of thrombocytes

ndash Activation of inflammation

bull Long term anti-angiogenetic

sup1 Hallahan et al Oncology (Huntingt) 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 53

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Prostate cancer

bull Reduction of pain and bleeding in hormone refractory

prostate cancer (Kynaston Br J Urol 1990 Kawakami Nippon

Hinyokika Gakkai Zasshi 1993 Kalapurakal Int J Radiat Oncol Biol Phys

2003)

bull 100 improvement in patients with important hematuria (Carlton J Urol 1972)

Bladder cancer (Srinivasan et al Clin Oncol (R Coll Radiol) 1994)

bull 17 Gy in 2 fractions3 days 59 clearance of hematuria

bull 45 Gy in 12 fractions26 days 16 clearance of

hematuria

bull Selection by performance status Palliation (pain and

hematuria) better with hypofractionated RT worse

survival

bull No important side effects

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 54

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung cancer

bull Control of hemoptysis in up to 80 of patients (Brundage

Can J Oncol 1996 Medical Research Council Lung Cancer Working Party

Br J Cancer 1992 Hoskin in Doyle et al Second Edition New York

Oxford University Press 1998 Langendijk Int J Radiat Oncol Biol Phys

2000)

bull Optimal dosefractionation

ndash Hypofractionated RT seems to be equally effective to multiple

fractions (Rees Clin Oncol (R Coll Radiol) 1997 Sundstrom JCO

2004 Phase III Stevens Australas Radiol 1995 Phase III studies of

the MRC (s above)

ndash 10 Gy Single fraction equally effective to multiple fractions less

toxic (Hoskin in Doyle et al Second Edition New York Oxford

University Press 1998 Medical Research Council Lung Cancer

Working Party Br J Cancer 1992)

ndash Mostly total dose of around 20 Gy (multiple fractions) or 8 Gy

single fraction recommended

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 55

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Van Lonkhuijzen

Radiother Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 56

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gynaecologic tumours

bull Cf review van Lonkhuijzen Radiother Oncol 2011

bull Consider intracavitary HDR brachytherapy

Rectal cancer

bull Up to 85 control of rectal bleeding (Hoskin in Doyle et al Second Edition New York Oxford University Press 1998)

Kaposi sarcoma

bull Good palliation for pain bleeding or edema TD 15-40 Gy SD 2 Gy gt90 response 70 complete remission (Review Becker et al Onkologie 2006)

Skin tumours (Miller in Doyle Oxford Textbook of Palliative Medicine New York Oxford University Press 1993)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 57

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duration of treatment effect

Lung cancer

bull Median duration of palliation 50 of remaining life span (30 Gy10d

27 Gy6d 17 Gy2 fract1w apart) (Medical Research Council Br J

Cancer 1991)

bull 1 fract 10 Gy vs 2 fract 85 Gy more patients need repeat RT (Medical Research Council Lung Cancer Working Party Br J Cancer 1992)

bull 417 pat need repeat RT within 3 m after 1x10 Gy (Scolaro Radiol

Med 1995)

Rec ovarian cancer

bull Median duration of palliation 4 m in 90 of patients until death (Corn Cancer 1994)

Cervical endometrial cancer

bull In 50 of patients pall Effect until death with 1-2x10 Gy

ndash Halle IJROBP 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 58

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull RT effective for improvement of

ndashThoracic symptoms (haemoptysis cough thoracic pain

dyspnoea airway obstruction) (Sirzeacuten Acta Oncol 2003 and others)

ndashQOL in about 13 of patients (Langendijk IJROBP 2000)

RT schedules

bull Systematic review (Fairchild JCO 264001-4011 2008)

ndash13 randomized trials 3473 patients

ndashdifferent RT schedules

ndashAim find optimal RT schedule for maximal palliation with

minimal toxicityneed for reirradiation

Thoracic symptoms

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 59

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz

Cancer

2007

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz Chow Hartsell Konski Cancer 2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 61

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemoptysis

bull Fig2 toux

733 689

812 802

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 62

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig3 doul thor 321 279

535 482

Cough

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 63

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 4 overall symptom burden

575 519

648 638

Thoracic pain

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 64

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 5 survie 1a

Cutoff (sensitivity analysis) BED[10] 35Gy vs LD

100 162

555 609

Overall symptom burden

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 65

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cutoff BED[10] 35Gy vs LD

265 217

Overall survival at 1y

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 66

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 7 Tox dysphagie

Cutoff BED[10] 30Gy vs LD

205 149

about x 2

Toxicity (dysphagia)

Fairchild JCO 2008

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomized trial 250 patients (Falk BMJ 2002)

bull Locally advanced non resectable NSCLC with minimal thoracic symptoms

bull Immediate vs delayed RT (at symptom onset)

bull In delayed arm 56 of patients died without RT

bull No difference in QOL odr OS

bull More acute toxicity in immediate RT arm

Randomized trial (Sundstrom Radiother Oncol 2005)

bull Advanced NSCLC

bull 2 RT schedules (5x4Gy vs 2x85 Gy) immediate RT

bull Stratification according to presenceabsence of thoracic symptoms

bull In asymptomatic patients no long term symptom control but important dysphagia

Timing

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 68

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull in 97 malignant

bull in 5-10 of lung cancer patients

bull Histology (exclude benign disease RT-chemosensible tumours

bull Generally spontanous improvement of symptoms by formation of collaterals

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 69

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Treatment

1 symptomatic

bull steroids

bull diuretics

bull Elevation of headthorax

2 causal bull chemotherapy (SCLC

lymphomas germinal tumours)

bull Endovascular stent placement

bull radiotherapy Palliative care in lung cancer ACCP

evidence- based clinical practice guidelines

(2nd edition)

Kvale Chest 2007

Superior vena cava syndrome

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

Radiotherapy

bull Mostly clinical response within 72 h

bull Complete clinical response at 2 w in 78 of patients with SCLC

and 63 of patients with NSCLC

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

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Duhamel Atlas clinique des maladies

des voies aeacuteriennes Elsevier

wwwupmccancercenterscom

Endobronchial brachytherapy

Cochrane analysis (Cardona The Cochrane

Library 2008)

bull No improved

symptom relief by

addition of

endobronchial

brachytherapy to

EBRT

bull Indicated in selected

patients pretreated

by EBRT with

central

endobronchial

obstruction

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Ozkok Lung Cancer 2008

Endobronchial brachytherapy

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Take home lung cancer

Dosefractionation

bull Minimum 10x3 Gy 5xw or equivalent

ndash better symptom control and better overall survival

ndash But more toxicity

bull Short schedule for symptom control and limited toxicity

ndashPoor performance status limited life expectancy

Timing

bull RT at the moment of symptom onset

bull No place for bdquoprophylactic palliative RTldquo according to evidence based guidelines

ndashExceptions

bull Young patient good PS aim of local control

bull Imminent symptoms (superior vena cava syndrome central airway obstruction

Rodrigues Pract Rad Oncol 2011

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

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Homs Eur J CancerLancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

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Randomisierte Studien

Homs Lancet 2004

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Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

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Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

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Scoccianti Radiother Oncol 2012

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Maranzano Radiother Oncol 2009

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Maranzano Radiother Oncol 2009

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

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Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 50

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Brain metastases

bull SRO tutorial CNS PD Dr A Pica

bull ScocciantiRicardi Radiother Oncol 2012 Review

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 51

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemorrhage

bull Bleeding in 6-10 of patients with advanced

cancer (Pereira et al Topics in Palliative Care Vol 4 New York

Oxford University Press 2000)

bull haemoptysis

bull haematemesis

bull haematocheziamelaena

bull vaginal bleeding

bull haematuria

bull bleeding in ulcerated skin lesions

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 52

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Mechanisms of haemostatic radiotherapy

bull Sparse literature

bull Coagulation activationsup1

ndash Oxydative endothelial damage

ndash Activation of thrombocytes

ndash Activation of inflammation

bull Long term anti-angiogenetic

sup1 Hallahan et al Oncology (Huntingt) 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 53

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Prostate cancer

bull Reduction of pain and bleeding in hormone refractory

prostate cancer (Kynaston Br J Urol 1990 Kawakami Nippon

Hinyokika Gakkai Zasshi 1993 Kalapurakal Int J Radiat Oncol Biol Phys

2003)

bull 100 improvement in patients with important hematuria (Carlton J Urol 1972)

Bladder cancer (Srinivasan et al Clin Oncol (R Coll Radiol) 1994)

bull 17 Gy in 2 fractions3 days 59 clearance of hematuria

bull 45 Gy in 12 fractions26 days 16 clearance of

hematuria

bull Selection by performance status Palliation (pain and

hematuria) better with hypofractionated RT worse

survival

bull No important side effects

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 54

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung cancer

bull Control of hemoptysis in up to 80 of patients (Brundage

Can J Oncol 1996 Medical Research Council Lung Cancer Working Party

Br J Cancer 1992 Hoskin in Doyle et al Second Edition New York

Oxford University Press 1998 Langendijk Int J Radiat Oncol Biol Phys

2000)

bull Optimal dosefractionation

ndash Hypofractionated RT seems to be equally effective to multiple

fractions (Rees Clin Oncol (R Coll Radiol) 1997 Sundstrom JCO

2004 Phase III Stevens Australas Radiol 1995 Phase III studies of

the MRC (s above)

ndash 10 Gy Single fraction equally effective to multiple fractions less

toxic (Hoskin in Doyle et al Second Edition New York Oxford

University Press 1998 Medical Research Council Lung Cancer

Working Party Br J Cancer 1992)

ndash Mostly total dose of around 20 Gy (multiple fractions) or 8 Gy

single fraction recommended

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 55

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Van Lonkhuijzen

Radiother Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 56

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gynaecologic tumours

bull Cf review van Lonkhuijzen Radiother Oncol 2011

bull Consider intracavitary HDR brachytherapy

Rectal cancer

bull Up to 85 control of rectal bleeding (Hoskin in Doyle et al Second Edition New York Oxford University Press 1998)

Kaposi sarcoma

bull Good palliation for pain bleeding or edema TD 15-40 Gy SD 2 Gy gt90 response 70 complete remission (Review Becker et al Onkologie 2006)

Skin tumours (Miller in Doyle Oxford Textbook of Palliative Medicine New York Oxford University Press 1993)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 57

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duration of treatment effect

Lung cancer

bull Median duration of palliation 50 of remaining life span (30 Gy10d

27 Gy6d 17 Gy2 fract1w apart) (Medical Research Council Br J

Cancer 1991)

bull 1 fract 10 Gy vs 2 fract 85 Gy more patients need repeat RT (Medical Research Council Lung Cancer Working Party Br J Cancer 1992)

bull 417 pat need repeat RT within 3 m after 1x10 Gy (Scolaro Radiol

Med 1995)

Rec ovarian cancer

bull Median duration of palliation 4 m in 90 of patients until death (Corn Cancer 1994)

Cervical endometrial cancer

bull In 50 of patients pall Effect until death with 1-2x10 Gy

ndash Halle IJROBP 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 58

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull RT effective for improvement of

ndashThoracic symptoms (haemoptysis cough thoracic pain

dyspnoea airway obstruction) (Sirzeacuten Acta Oncol 2003 and others)

ndashQOL in about 13 of patients (Langendijk IJROBP 2000)

RT schedules

bull Systematic review (Fairchild JCO 264001-4011 2008)

ndash13 randomized trials 3473 patients

ndashdifferent RT schedules

ndashAim find optimal RT schedule for maximal palliation with

minimal toxicityneed for reirradiation

Thoracic symptoms

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 59

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz

Cancer

2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 60

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz Chow Hartsell Konski Cancer 2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 61

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemoptysis

bull Fig2 toux

733 689

812 802

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 62

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig3 doul thor 321 279

535 482

Cough

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 63

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 4 overall symptom burden

575 519

648 638

Thoracic pain

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 64

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 5 survie 1a

Cutoff (sensitivity analysis) BED[10] 35Gy vs LD

100 162

555 609

Overall symptom burden

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 65

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cutoff BED[10] 35Gy vs LD

265 217

Overall survival at 1y

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 66

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 7 Tox dysphagie

Cutoff BED[10] 30Gy vs LD

205 149

about x 2

Toxicity (dysphagia)

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 67

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomized trial 250 patients (Falk BMJ 2002)

bull Locally advanced non resectable NSCLC with minimal thoracic symptoms

bull Immediate vs delayed RT (at symptom onset)

bull In delayed arm 56 of patients died without RT

bull No difference in QOL odr OS

bull More acute toxicity in immediate RT arm

Randomized trial (Sundstrom Radiother Oncol 2005)

bull Advanced NSCLC

bull 2 RT schedules (5x4Gy vs 2x85 Gy) immediate RT

bull Stratification according to presenceabsence of thoracic symptoms

bull In asymptomatic patients no long term symptom control but important dysphagia

Timing

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 68

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull in 97 malignant

bull in 5-10 of lung cancer patients

bull Histology (exclude benign disease RT-chemosensible tumours

bull Generally spontanous improvement of symptoms by formation of collaterals

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 69

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Treatment

1 symptomatic

bull steroids

bull diuretics

bull Elevation of headthorax

2 causal bull chemotherapy (SCLC

lymphomas germinal tumours)

bull Endovascular stent placement

bull radiotherapy Palliative care in lung cancer ACCP

evidence- based clinical practice guidelines

(2nd edition)

Kvale Chest 2007

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 70

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

Radiotherapy

bull Mostly clinical response within 72 h

bull Complete clinical response at 2 w in 78 of patients with SCLC

and 63 of patients with NSCLC

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 71

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 72

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 73

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duhamel Atlas clinique des maladies

des voies aeacuteriennes Elsevier

wwwupmccancercenterscom

Endobronchial brachytherapy

Cochrane analysis (Cardona The Cochrane

Library 2008)

bull No improved

symptom relief by

addition of

endobronchial

brachytherapy to

EBRT

bull Indicated in selected

patients pretreated

by EBRT with

central

endobronchial

obstruction

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 74

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Ozkok Lung Cancer 2008

Endobronchial brachytherapy

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 75

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Take home lung cancer

Dosefractionation

bull Minimum 10x3 Gy 5xw or equivalent

ndash better symptom control and better overall survival

ndash But more toxicity

bull Short schedule for symptom control and limited toxicity

ndashPoor performance status limited life expectancy

Timing

bull RT at the moment of symptom onset

bull No place for bdquoprophylactic palliative RTldquo according to evidence based guidelines

ndashExceptions

bull Young patient good PS aim of local control

bull Imminent symptoms (superior vena cava syndrome central airway obstruction

Rodrigues Pract Rad Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 76

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 77

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 78

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 80

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 81

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 82

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 83

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 84

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 85

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 90

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 99

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Scoccianti Radiother Oncol 2012

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 101

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 102

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 103

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 104

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Page 46: SRO Tutorial Palliative Care 04.05.2012 Palliative Radiotherapy · 2018-02-22 · SRO Tutorial Palliative Care – Palliative Radiotherapy 30 Jacqueline Vock, Universitätsklinik

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Maranzano Radiother Oncol 2009

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 47

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 48

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 49

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 50

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull SRO tutorial CNS PD Dr A Pica

bull ScocciantiRicardi Radiother Oncol 2012 Review

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 51

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemorrhage

bull Bleeding in 6-10 of patients with advanced

cancer (Pereira et al Topics in Palliative Care Vol 4 New York

Oxford University Press 2000)

bull haemoptysis

bull haematemesis

bull haematocheziamelaena

bull vaginal bleeding

bull haematuria

bull bleeding in ulcerated skin lesions

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 52

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Mechanisms of haemostatic radiotherapy

bull Sparse literature

bull Coagulation activationsup1

ndash Oxydative endothelial damage

ndash Activation of thrombocytes

ndash Activation of inflammation

bull Long term anti-angiogenetic

sup1 Hallahan et al Oncology (Huntingt) 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 53

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Prostate cancer

bull Reduction of pain and bleeding in hormone refractory

prostate cancer (Kynaston Br J Urol 1990 Kawakami Nippon

Hinyokika Gakkai Zasshi 1993 Kalapurakal Int J Radiat Oncol Biol Phys

2003)

bull 100 improvement in patients with important hematuria (Carlton J Urol 1972)

Bladder cancer (Srinivasan et al Clin Oncol (R Coll Radiol) 1994)

bull 17 Gy in 2 fractions3 days 59 clearance of hematuria

bull 45 Gy in 12 fractions26 days 16 clearance of

hematuria

bull Selection by performance status Palliation (pain and

hematuria) better with hypofractionated RT worse

survival

bull No important side effects

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 54

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung cancer

bull Control of hemoptysis in up to 80 of patients (Brundage

Can J Oncol 1996 Medical Research Council Lung Cancer Working Party

Br J Cancer 1992 Hoskin in Doyle et al Second Edition New York

Oxford University Press 1998 Langendijk Int J Radiat Oncol Biol Phys

2000)

bull Optimal dosefractionation

ndash Hypofractionated RT seems to be equally effective to multiple

fractions (Rees Clin Oncol (R Coll Radiol) 1997 Sundstrom JCO

2004 Phase III Stevens Australas Radiol 1995 Phase III studies of

the MRC (s above)

ndash 10 Gy Single fraction equally effective to multiple fractions less

toxic (Hoskin in Doyle et al Second Edition New York Oxford

University Press 1998 Medical Research Council Lung Cancer

Working Party Br J Cancer 1992)

ndash Mostly total dose of around 20 Gy (multiple fractions) or 8 Gy

single fraction recommended

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 55

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Van Lonkhuijzen

Radiother Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 56

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gynaecologic tumours

bull Cf review van Lonkhuijzen Radiother Oncol 2011

bull Consider intracavitary HDR brachytherapy

Rectal cancer

bull Up to 85 control of rectal bleeding (Hoskin in Doyle et al Second Edition New York Oxford University Press 1998)

Kaposi sarcoma

bull Good palliation for pain bleeding or edema TD 15-40 Gy SD 2 Gy gt90 response 70 complete remission (Review Becker et al Onkologie 2006)

Skin tumours (Miller in Doyle Oxford Textbook of Palliative Medicine New York Oxford University Press 1993)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 57

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duration of treatment effect

Lung cancer

bull Median duration of palliation 50 of remaining life span (30 Gy10d

27 Gy6d 17 Gy2 fract1w apart) (Medical Research Council Br J

Cancer 1991)

bull 1 fract 10 Gy vs 2 fract 85 Gy more patients need repeat RT (Medical Research Council Lung Cancer Working Party Br J Cancer 1992)

bull 417 pat need repeat RT within 3 m after 1x10 Gy (Scolaro Radiol

Med 1995)

Rec ovarian cancer

bull Median duration of palliation 4 m in 90 of patients until death (Corn Cancer 1994)

Cervical endometrial cancer

bull In 50 of patients pall Effect until death with 1-2x10 Gy

ndash Halle IJROBP 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 58

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull RT effective for improvement of

ndashThoracic symptoms (haemoptysis cough thoracic pain

dyspnoea airway obstruction) (Sirzeacuten Acta Oncol 2003 and others)

ndashQOL in about 13 of patients (Langendijk IJROBP 2000)

RT schedules

bull Systematic review (Fairchild JCO 264001-4011 2008)

ndash13 randomized trials 3473 patients

ndashdifferent RT schedules

ndashAim find optimal RT schedule for maximal palliation with

minimal toxicityneed for reirradiation

Thoracic symptoms

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 59

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz

Cancer

2007

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz Chow Hartsell Konski Cancer 2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 61

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemoptysis

bull Fig2 toux

733 689

812 802

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 62

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig3 doul thor 321 279

535 482

Cough

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 63

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 4 overall symptom burden

575 519

648 638

Thoracic pain

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 64

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 5 survie 1a

Cutoff (sensitivity analysis) BED[10] 35Gy vs LD

100 162

555 609

Overall symptom burden

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 65

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cutoff BED[10] 35Gy vs LD

265 217

Overall survival at 1y

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 66

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 7 Tox dysphagie

Cutoff BED[10] 30Gy vs LD

205 149

about x 2

Toxicity (dysphagia)

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 67

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomized trial 250 patients (Falk BMJ 2002)

bull Locally advanced non resectable NSCLC with minimal thoracic symptoms

bull Immediate vs delayed RT (at symptom onset)

bull In delayed arm 56 of patients died without RT

bull No difference in QOL odr OS

bull More acute toxicity in immediate RT arm

Randomized trial (Sundstrom Radiother Oncol 2005)

bull Advanced NSCLC

bull 2 RT schedules (5x4Gy vs 2x85 Gy) immediate RT

bull Stratification according to presenceabsence of thoracic symptoms

bull In asymptomatic patients no long term symptom control but important dysphagia

Timing

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 68

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull in 97 malignant

bull in 5-10 of lung cancer patients

bull Histology (exclude benign disease RT-chemosensible tumours

bull Generally spontanous improvement of symptoms by formation of collaterals

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 69

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Treatment

1 symptomatic

bull steroids

bull diuretics

bull Elevation of headthorax

2 causal bull chemotherapy (SCLC

lymphomas germinal tumours)

bull Endovascular stent placement

bull radiotherapy Palliative care in lung cancer ACCP

evidence- based clinical practice guidelines

(2nd edition)

Kvale Chest 2007

Superior vena cava syndrome

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

Radiotherapy

bull Mostly clinical response within 72 h

bull Complete clinical response at 2 w in 78 of patients with SCLC

and 63 of patients with NSCLC

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 73

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duhamel Atlas clinique des maladies

des voies aeacuteriennes Elsevier

wwwupmccancercenterscom

Endobronchial brachytherapy

Cochrane analysis (Cardona The Cochrane

Library 2008)

bull No improved

symptom relief by

addition of

endobronchial

brachytherapy to

EBRT

bull Indicated in selected

patients pretreated

by EBRT with

central

endobronchial

obstruction

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Ozkok Lung Cancer 2008

Endobronchial brachytherapy

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Take home lung cancer

Dosefractionation

bull Minimum 10x3 Gy 5xw or equivalent

ndash better symptom control and better overall survival

ndash But more toxicity

bull Short schedule for symptom control and limited toxicity

ndashPoor performance status limited life expectancy

Timing

bull RT at the moment of symptom onset

bull No place for bdquoprophylactic palliative RTldquo according to evidence based guidelines

ndashExceptions

bull Young patient good PS aim of local control

bull Imminent symptoms (superior vena cava syndrome central airway obstruction

Rodrigues Pract Rad Oncol 2011

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

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Homs Eur J CancerLancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

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Scoccianti Radiother Oncol 2012

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 102

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz IJROBP 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 48

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 50

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull SRO tutorial CNS PD Dr A Pica

bull ScocciantiRicardi Radiother Oncol 2012 Review

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 51

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemorrhage

bull Bleeding in 6-10 of patients with advanced

cancer (Pereira et al Topics in Palliative Care Vol 4 New York

Oxford University Press 2000)

bull haemoptysis

bull haematemesis

bull haematocheziamelaena

bull vaginal bleeding

bull haematuria

bull bleeding in ulcerated skin lesions

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 52

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Mechanisms of haemostatic radiotherapy

bull Sparse literature

bull Coagulation activationsup1

ndash Oxydative endothelial damage

ndash Activation of thrombocytes

ndash Activation of inflammation

bull Long term anti-angiogenetic

sup1 Hallahan et al Oncology (Huntingt) 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 53

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Prostate cancer

bull Reduction of pain and bleeding in hormone refractory

prostate cancer (Kynaston Br J Urol 1990 Kawakami Nippon

Hinyokika Gakkai Zasshi 1993 Kalapurakal Int J Radiat Oncol Biol Phys

2003)

bull 100 improvement in patients with important hematuria (Carlton J Urol 1972)

Bladder cancer (Srinivasan et al Clin Oncol (R Coll Radiol) 1994)

bull 17 Gy in 2 fractions3 days 59 clearance of hematuria

bull 45 Gy in 12 fractions26 days 16 clearance of

hematuria

bull Selection by performance status Palliation (pain and

hematuria) better with hypofractionated RT worse

survival

bull No important side effects

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 54

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung cancer

bull Control of hemoptysis in up to 80 of patients (Brundage

Can J Oncol 1996 Medical Research Council Lung Cancer Working Party

Br J Cancer 1992 Hoskin in Doyle et al Second Edition New York

Oxford University Press 1998 Langendijk Int J Radiat Oncol Biol Phys

2000)

bull Optimal dosefractionation

ndash Hypofractionated RT seems to be equally effective to multiple

fractions (Rees Clin Oncol (R Coll Radiol) 1997 Sundstrom JCO

2004 Phase III Stevens Australas Radiol 1995 Phase III studies of

the MRC (s above)

ndash 10 Gy Single fraction equally effective to multiple fractions less

toxic (Hoskin in Doyle et al Second Edition New York Oxford

University Press 1998 Medical Research Council Lung Cancer

Working Party Br J Cancer 1992)

ndash Mostly total dose of around 20 Gy (multiple fractions) or 8 Gy

single fraction recommended

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 55

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Van Lonkhuijzen

Radiother Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 56

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gynaecologic tumours

bull Cf review van Lonkhuijzen Radiother Oncol 2011

bull Consider intracavitary HDR brachytherapy

Rectal cancer

bull Up to 85 control of rectal bleeding (Hoskin in Doyle et al Second Edition New York Oxford University Press 1998)

Kaposi sarcoma

bull Good palliation for pain bleeding or edema TD 15-40 Gy SD 2 Gy gt90 response 70 complete remission (Review Becker et al Onkologie 2006)

Skin tumours (Miller in Doyle Oxford Textbook of Palliative Medicine New York Oxford University Press 1993)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 57

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duration of treatment effect

Lung cancer

bull Median duration of palliation 50 of remaining life span (30 Gy10d

27 Gy6d 17 Gy2 fract1w apart) (Medical Research Council Br J

Cancer 1991)

bull 1 fract 10 Gy vs 2 fract 85 Gy more patients need repeat RT (Medical Research Council Lung Cancer Working Party Br J Cancer 1992)

bull 417 pat need repeat RT within 3 m after 1x10 Gy (Scolaro Radiol

Med 1995)

Rec ovarian cancer

bull Median duration of palliation 4 m in 90 of patients until death (Corn Cancer 1994)

Cervical endometrial cancer

bull In 50 of patients pall Effect until death with 1-2x10 Gy

ndash Halle IJROBP 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 58

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull RT effective for improvement of

ndashThoracic symptoms (haemoptysis cough thoracic pain

dyspnoea airway obstruction) (Sirzeacuten Acta Oncol 2003 and others)

ndashQOL in about 13 of patients (Langendijk IJROBP 2000)

RT schedules

bull Systematic review (Fairchild JCO 264001-4011 2008)

ndash13 randomized trials 3473 patients

ndashdifferent RT schedules

ndashAim find optimal RT schedule for maximal palliation with

minimal toxicityneed for reirradiation

Thoracic symptoms

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 59

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz

Cancer

2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 60

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz Chow Hartsell Konski Cancer 2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 61

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemoptysis

bull Fig2 toux

733 689

812 802

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 62

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig3 doul thor 321 279

535 482

Cough

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 63

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 4 overall symptom burden

575 519

648 638

Thoracic pain

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 64

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 5 survie 1a

Cutoff (sensitivity analysis) BED[10] 35Gy vs LD

100 162

555 609

Overall symptom burden

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 65

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cutoff BED[10] 35Gy vs LD

265 217

Overall survival at 1y

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 66

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 7 Tox dysphagie

Cutoff BED[10] 30Gy vs LD

205 149

about x 2

Toxicity (dysphagia)

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 67

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomized trial 250 patients (Falk BMJ 2002)

bull Locally advanced non resectable NSCLC with minimal thoracic symptoms

bull Immediate vs delayed RT (at symptom onset)

bull In delayed arm 56 of patients died without RT

bull No difference in QOL odr OS

bull More acute toxicity in immediate RT arm

Randomized trial (Sundstrom Radiother Oncol 2005)

bull Advanced NSCLC

bull 2 RT schedules (5x4Gy vs 2x85 Gy) immediate RT

bull Stratification according to presenceabsence of thoracic symptoms

bull In asymptomatic patients no long term symptom control but important dysphagia

Timing

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 68

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull in 97 malignant

bull in 5-10 of lung cancer patients

bull Histology (exclude benign disease RT-chemosensible tumours

bull Generally spontanous improvement of symptoms by formation of collaterals

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 69

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Treatment

1 symptomatic

bull steroids

bull diuretics

bull Elevation of headthorax

2 causal bull chemotherapy (SCLC

lymphomas germinal tumours)

bull Endovascular stent placement

bull radiotherapy Palliative care in lung cancer ACCP

evidence- based clinical practice guidelines

(2nd edition)

Kvale Chest 2007

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 70

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

Radiotherapy

bull Mostly clinical response within 72 h

bull Complete clinical response at 2 w in 78 of patients with SCLC

and 63 of patients with NSCLC

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 71

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 72

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 73

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duhamel Atlas clinique des maladies

des voies aeacuteriennes Elsevier

wwwupmccancercenterscom

Endobronchial brachytherapy

Cochrane analysis (Cardona The Cochrane

Library 2008)

bull No improved

symptom relief by

addition of

endobronchial

brachytherapy to

EBRT

bull Indicated in selected

patients pretreated

by EBRT with

central

endobronchial

obstruction

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 74

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Ozkok Lung Cancer 2008

Endobronchial brachytherapy

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 75

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Take home lung cancer

Dosefractionation

bull Minimum 10x3 Gy 5xw or equivalent

ndash better symptom control and better overall survival

ndash But more toxicity

bull Short schedule for symptom control and limited toxicity

ndashPoor performance status limited life expectancy

Timing

bull RT at the moment of symptom onset

bull No place for bdquoprophylactic palliative RTldquo according to evidence based guidelines

ndashExceptions

bull Young patient good PS aim of local control

bull Imminent symptoms (superior vena cava syndrome central airway obstruction

Rodrigues Pract Rad Oncol 2011

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 77

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 80

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 82

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 83

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 84

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 85

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 90

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 99

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Scoccianti Radiother Oncol 2012

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 101

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 102

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Page 48: SRO Tutorial Palliative Care 04.05.2012 Palliative Radiotherapy · 2018-02-22 · SRO Tutorial Palliative Care – Palliative Radiotherapy 30 Jacqueline Vock, Universitätsklinik

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 49

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 50

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull SRO tutorial CNS PD Dr A Pica

bull ScocciantiRicardi Radiother Oncol 2012 Review

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 51

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemorrhage

bull Bleeding in 6-10 of patients with advanced

cancer (Pereira et al Topics in Palliative Care Vol 4 New York

Oxford University Press 2000)

bull haemoptysis

bull haematemesis

bull haematocheziamelaena

bull vaginal bleeding

bull haematuria

bull bleeding in ulcerated skin lesions

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 52

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Mechanisms of haemostatic radiotherapy

bull Sparse literature

bull Coagulation activationsup1

ndash Oxydative endothelial damage

ndash Activation of thrombocytes

ndash Activation of inflammation

bull Long term anti-angiogenetic

sup1 Hallahan et al Oncology (Huntingt) 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 53

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Prostate cancer

bull Reduction of pain and bleeding in hormone refractory

prostate cancer (Kynaston Br J Urol 1990 Kawakami Nippon

Hinyokika Gakkai Zasshi 1993 Kalapurakal Int J Radiat Oncol Biol Phys

2003)

bull 100 improvement in patients with important hematuria (Carlton J Urol 1972)

Bladder cancer (Srinivasan et al Clin Oncol (R Coll Radiol) 1994)

bull 17 Gy in 2 fractions3 days 59 clearance of hematuria

bull 45 Gy in 12 fractions26 days 16 clearance of

hematuria

bull Selection by performance status Palliation (pain and

hematuria) better with hypofractionated RT worse

survival

bull No important side effects

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 54

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung cancer

bull Control of hemoptysis in up to 80 of patients (Brundage

Can J Oncol 1996 Medical Research Council Lung Cancer Working Party

Br J Cancer 1992 Hoskin in Doyle et al Second Edition New York

Oxford University Press 1998 Langendijk Int J Radiat Oncol Biol Phys

2000)

bull Optimal dosefractionation

ndash Hypofractionated RT seems to be equally effective to multiple

fractions (Rees Clin Oncol (R Coll Radiol) 1997 Sundstrom JCO

2004 Phase III Stevens Australas Radiol 1995 Phase III studies of

the MRC (s above)

ndash 10 Gy Single fraction equally effective to multiple fractions less

toxic (Hoskin in Doyle et al Second Edition New York Oxford

University Press 1998 Medical Research Council Lung Cancer

Working Party Br J Cancer 1992)

ndash Mostly total dose of around 20 Gy (multiple fractions) or 8 Gy

single fraction recommended

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 55

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Van Lonkhuijzen

Radiother Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 56

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gynaecologic tumours

bull Cf review van Lonkhuijzen Radiother Oncol 2011

bull Consider intracavitary HDR brachytherapy

Rectal cancer

bull Up to 85 control of rectal bleeding (Hoskin in Doyle et al Second Edition New York Oxford University Press 1998)

Kaposi sarcoma

bull Good palliation for pain bleeding or edema TD 15-40 Gy SD 2 Gy gt90 response 70 complete remission (Review Becker et al Onkologie 2006)

Skin tumours (Miller in Doyle Oxford Textbook of Palliative Medicine New York Oxford University Press 1993)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 57

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duration of treatment effect

Lung cancer

bull Median duration of palliation 50 of remaining life span (30 Gy10d

27 Gy6d 17 Gy2 fract1w apart) (Medical Research Council Br J

Cancer 1991)

bull 1 fract 10 Gy vs 2 fract 85 Gy more patients need repeat RT (Medical Research Council Lung Cancer Working Party Br J Cancer 1992)

bull 417 pat need repeat RT within 3 m after 1x10 Gy (Scolaro Radiol

Med 1995)

Rec ovarian cancer

bull Median duration of palliation 4 m in 90 of patients until death (Corn Cancer 1994)

Cervical endometrial cancer

bull In 50 of patients pall Effect until death with 1-2x10 Gy

ndash Halle IJROBP 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 58

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull RT effective for improvement of

ndashThoracic symptoms (haemoptysis cough thoracic pain

dyspnoea airway obstruction) (Sirzeacuten Acta Oncol 2003 and others)

ndashQOL in about 13 of patients (Langendijk IJROBP 2000)

RT schedules

bull Systematic review (Fairchild JCO 264001-4011 2008)

ndash13 randomized trials 3473 patients

ndashdifferent RT schedules

ndashAim find optimal RT schedule for maximal palliation with

minimal toxicityneed for reirradiation

Thoracic symptoms

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 59

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz

Cancer

2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 60

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz Chow Hartsell Konski Cancer 2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 61

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemoptysis

bull Fig2 toux

733 689

812 802

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 62

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig3 doul thor 321 279

535 482

Cough

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 63

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 4 overall symptom burden

575 519

648 638

Thoracic pain

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 64

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 5 survie 1a

Cutoff (sensitivity analysis) BED[10] 35Gy vs LD

100 162

555 609

Overall symptom burden

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 65

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cutoff BED[10] 35Gy vs LD

265 217

Overall survival at 1y

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 66

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 7 Tox dysphagie

Cutoff BED[10] 30Gy vs LD

205 149

about x 2

Toxicity (dysphagia)

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 67

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomized trial 250 patients (Falk BMJ 2002)

bull Locally advanced non resectable NSCLC with minimal thoracic symptoms

bull Immediate vs delayed RT (at symptom onset)

bull In delayed arm 56 of patients died without RT

bull No difference in QOL odr OS

bull More acute toxicity in immediate RT arm

Randomized trial (Sundstrom Radiother Oncol 2005)

bull Advanced NSCLC

bull 2 RT schedules (5x4Gy vs 2x85 Gy) immediate RT

bull Stratification according to presenceabsence of thoracic symptoms

bull In asymptomatic patients no long term symptom control but important dysphagia

Timing

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 68

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull in 97 malignant

bull in 5-10 of lung cancer patients

bull Histology (exclude benign disease RT-chemosensible tumours

bull Generally spontanous improvement of symptoms by formation of collaterals

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 69

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Treatment

1 symptomatic

bull steroids

bull diuretics

bull Elevation of headthorax

2 causal bull chemotherapy (SCLC

lymphomas germinal tumours)

bull Endovascular stent placement

bull radiotherapy Palliative care in lung cancer ACCP

evidence- based clinical practice guidelines

(2nd edition)

Kvale Chest 2007

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 70

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

Radiotherapy

bull Mostly clinical response within 72 h

bull Complete clinical response at 2 w in 78 of patients with SCLC

and 63 of patients with NSCLC

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 71

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 72

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 73

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duhamel Atlas clinique des maladies

des voies aeacuteriennes Elsevier

wwwupmccancercenterscom

Endobronchial brachytherapy

Cochrane analysis (Cardona The Cochrane

Library 2008)

bull No improved

symptom relief by

addition of

endobronchial

brachytherapy to

EBRT

bull Indicated in selected

patients pretreated

by EBRT with

central

endobronchial

obstruction

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 74

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Ozkok Lung Cancer 2008

Endobronchial brachytherapy

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 75

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Take home lung cancer

Dosefractionation

bull Minimum 10x3 Gy 5xw or equivalent

ndash better symptom control and better overall survival

ndash But more toxicity

bull Short schedule for symptom control and limited toxicity

ndashPoor performance status limited life expectancy

Timing

bull RT at the moment of symptom onset

bull No place for bdquoprophylactic palliative RTldquo according to evidence based guidelines

ndashExceptions

bull Young patient good PS aim of local control

bull Imminent symptoms (superior vena cava syndrome central airway obstruction

Rodrigues Pract Rad Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 76

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 77

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 78

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 80

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 81

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 82

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 83

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 84

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 85

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 90

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 98

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 99

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Scoccianti Radiother Oncol 2012

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 100

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SRO Tutorial Palliative Care ndash Palliative Radiotherapy 101

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 102

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 103

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Page 49: SRO Tutorial Palliative Care 04.05.2012 Palliative Radiotherapy · 2018-02-22 · SRO Tutorial Palliative Care – Palliative Radiotherapy 30 Jacqueline Vock, Universitätsklinik

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 49

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rades IJROBP 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 50

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull SRO tutorial CNS PD Dr A Pica

bull ScocciantiRicardi Radiother Oncol 2012 Review

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 51

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemorrhage

bull Bleeding in 6-10 of patients with advanced

cancer (Pereira et al Topics in Palliative Care Vol 4 New York

Oxford University Press 2000)

bull haemoptysis

bull haematemesis

bull haematocheziamelaena

bull vaginal bleeding

bull haematuria

bull bleeding in ulcerated skin lesions

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 52

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Mechanisms of haemostatic radiotherapy

bull Sparse literature

bull Coagulation activationsup1

ndash Oxydative endothelial damage

ndash Activation of thrombocytes

ndash Activation of inflammation

bull Long term anti-angiogenetic

sup1 Hallahan et al Oncology (Huntingt) 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 53

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Prostate cancer

bull Reduction of pain and bleeding in hormone refractory

prostate cancer (Kynaston Br J Urol 1990 Kawakami Nippon

Hinyokika Gakkai Zasshi 1993 Kalapurakal Int J Radiat Oncol Biol Phys

2003)

bull 100 improvement in patients with important hematuria (Carlton J Urol 1972)

Bladder cancer (Srinivasan et al Clin Oncol (R Coll Radiol) 1994)

bull 17 Gy in 2 fractions3 days 59 clearance of hematuria

bull 45 Gy in 12 fractions26 days 16 clearance of

hematuria

bull Selection by performance status Palliation (pain and

hematuria) better with hypofractionated RT worse

survival

bull No important side effects

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 54

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung cancer

bull Control of hemoptysis in up to 80 of patients (Brundage

Can J Oncol 1996 Medical Research Council Lung Cancer Working Party

Br J Cancer 1992 Hoskin in Doyle et al Second Edition New York

Oxford University Press 1998 Langendijk Int J Radiat Oncol Biol Phys

2000)

bull Optimal dosefractionation

ndash Hypofractionated RT seems to be equally effective to multiple

fractions (Rees Clin Oncol (R Coll Radiol) 1997 Sundstrom JCO

2004 Phase III Stevens Australas Radiol 1995 Phase III studies of

the MRC (s above)

ndash 10 Gy Single fraction equally effective to multiple fractions less

toxic (Hoskin in Doyle et al Second Edition New York Oxford

University Press 1998 Medical Research Council Lung Cancer

Working Party Br J Cancer 1992)

ndash Mostly total dose of around 20 Gy (multiple fractions) or 8 Gy

single fraction recommended

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 55

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Van Lonkhuijzen

Radiother Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 56

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gynaecologic tumours

bull Cf review van Lonkhuijzen Radiother Oncol 2011

bull Consider intracavitary HDR brachytherapy

Rectal cancer

bull Up to 85 control of rectal bleeding (Hoskin in Doyle et al Second Edition New York Oxford University Press 1998)

Kaposi sarcoma

bull Good palliation for pain bleeding or edema TD 15-40 Gy SD 2 Gy gt90 response 70 complete remission (Review Becker et al Onkologie 2006)

Skin tumours (Miller in Doyle Oxford Textbook of Palliative Medicine New York Oxford University Press 1993)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 57

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duration of treatment effect

Lung cancer

bull Median duration of palliation 50 of remaining life span (30 Gy10d

27 Gy6d 17 Gy2 fract1w apart) (Medical Research Council Br J

Cancer 1991)

bull 1 fract 10 Gy vs 2 fract 85 Gy more patients need repeat RT (Medical Research Council Lung Cancer Working Party Br J Cancer 1992)

bull 417 pat need repeat RT within 3 m after 1x10 Gy (Scolaro Radiol

Med 1995)

Rec ovarian cancer

bull Median duration of palliation 4 m in 90 of patients until death (Corn Cancer 1994)

Cervical endometrial cancer

bull In 50 of patients pall Effect until death with 1-2x10 Gy

ndash Halle IJROBP 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 58

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull RT effective for improvement of

ndashThoracic symptoms (haemoptysis cough thoracic pain

dyspnoea airway obstruction) (Sirzeacuten Acta Oncol 2003 and others)

ndashQOL in about 13 of patients (Langendijk IJROBP 2000)

RT schedules

bull Systematic review (Fairchild JCO 264001-4011 2008)

ndash13 randomized trials 3473 patients

ndashdifferent RT schedules

ndashAim find optimal RT schedule for maximal palliation with

minimal toxicityneed for reirradiation

Thoracic symptoms

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 59

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz

Cancer

2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 60

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz Chow Hartsell Konski Cancer 2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 61

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemoptysis

bull Fig2 toux

733 689

812 802

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 62

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig3 doul thor 321 279

535 482

Cough

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 63

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 4 overall symptom burden

575 519

648 638

Thoracic pain

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 64

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 5 survie 1a

Cutoff (sensitivity analysis) BED[10] 35Gy vs LD

100 162

555 609

Overall symptom burden

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 65

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cutoff BED[10] 35Gy vs LD

265 217

Overall survival at 1y

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 66

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 7 Tox dysphagie

Cutoff BED[10] 30Gy vs LD

205 149

about x 2

Toxicity (dysphagia)

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 67

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomized trial 250 patients (Falk BMJ 2002)

bull Locally advanced non resectable NSCLC with minimal thoracic symptoms

bull Immediate vs delayed RT (at symptom onset)

bull In delayed arm 56 of patients died without RT

bull No difference in QOL odr OS

bull More acute toxicity in immediate RT arm

Randomized trial (Sundstrom Radiother Oncol 2005)

bull Advanced NSCLC

bull 2 RT schedules (5x4Gy vs 2x85 Gy) immediate RT

bull Stratification according to presenceabsence of thoracic symptoms

bull In asymptomatic patients no long term symptom control but important dysphagia

Timing

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 68

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull in 97 malignant

bull in 5-10 of lung cancer patients

bull Histology (exclude benign disease RT-chemosensible tumours

bull Generally spontanous improvement of symptoms by formation of collaterals

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 69

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Treatment

1 symptomatic

bull steroids

bull diuretics

bull Elevation of headthorax

2 causal bull chemotherapy (SCLC

lymphomas germinal tumours)

bull Endovascular stent placement

bull radiotherapy Palliative care in lung cancer ACCP

evidence- based clinical practice guidelines

(2nd edition)

Kvale Chest 2007

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 70

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

Radiotherapy

bull Mostly clinical response within 72 h

bull Complete clinical response at 2 w in 78 of patients with SCLC

and 63 of patients with NSCLC

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 71

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 72

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 73

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duhamel Atlas clinique des maladies

des voies aeacuteriennes Elsevier

wwwupmccancercenterscom

Endobronchial brachytherapy

Cochrane analysis (Cardona The Cochrane

Library 2008)

bull No improved

symptom relief by

addition of

endobronchial

brachytherapy to

EBRT

bull Indicated in selected

patients pretreated

by EBRT with

central

endobronchial

obstruction

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 74

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Ozkok Lung Cancer 2008

Endobronchial brachytherapy

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 75

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Take home lung cancer

Dosefractionation

bull Minimum 10x3 Gy 5xw or equivalent

ndash better symptom control and better overall survival

ndash But more toxicity

bull Short schedule for symptom control and limited toxicity

ndashPoor performance status limited life expectancy

Timing

bull RT at the moment of symptom onset

bull No place for bdquoprophylactic palliative RTldquo according to evidence based guidelines

ndashExceptions

bull Young patient good PS aim of local control

bull Imminent symptoms (superior vena cava syndrome central airway obstruction

Rodrigues Pract Rad Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 76

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 77

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 78

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 80

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 81

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 82

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 83

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 84

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 85

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 90

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 98

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 99

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Scoccianti Radiother Oncol 2012

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SRO Tutorial Palliative Care ndash Palliative Radiotherapy 50

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull SRO tutorial CNS PD Dr A Pica

bull ScocciantiRicardi Radiother Oncol 2012 Review

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 51

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemorrhage

bull Bleeding in 6-10 of patients with advanced

cancer (Pereira et al Topics in Palliative Care Vol 4 New York

Oxford University Press 2000)

bull haemoptysis

bull haematemesis

bull haematocheziamelaena

bull vaginal bleeding

bull haematuria

bull bleeding in ulcerated skin lesions

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 52

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Mechanisms of haemostatic radiotherapy

bull Sparse literature

bull Coagulation activationsup1

ndash Oxydative endothelial damage

ndash Activation of thrombocytes

ndash Activation of inflammation

bull Long term anti-angiogenetic

sup1 Hallahan et al Oncology (Huntingt) 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 53

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Prostate cancer

bull Reduction of pain and bleeding in hormone refractory

prostate cancer (Kynaston Br J Urol 1990 Kawakami Nippon

Hinyokika Gakkai Zasshi 1993 Kalapurakal Int J Radiat Oncol Biol Phys

2003)

bull 100 improvement in patients with important hematuria (Carlton J Urol 1972)

Bladder cancer (Srinivasan et al Clin Oncol (R Coll Radiol) 1994)

bull 17 Gy in 2 fractions3 days 59 clearance of hematuria

bull 45 Gy in 12 fractions26 days 16 clearance of

hematuria

bull Selection by performance status Palliation (pain and

hematuria) better with hypofractionated RT worse

survival

bull No important side effects

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 54

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung cancer

bull Control of hemoptysis in up to 80 of patients (Brundage

Can J Oncol 1996 Medical Research Council Lung Cancer Working Party

Br J Cancer 1992 Hoskin in Doyle et al Second Edition New York

Oxford University Press 1998 Langendijk Int J Radiat Oncol Biol Phys

2000)

bull Optimal dosefractionation

ndash Hypofractionated RT seems to be equally effective to multiple

fractions (Rees Clin Oncol (R Coll Radiol) 1997 Sundstrom JCO

2004 Phase III Stevens Australas Radiol 1995 Phase III studies of

the MRC (s above)

ndash 10 Gy Single fraction equally effective to multiple fractions less

toxic (Hoskin in Doyle et al Second Edition New York Oxford

University Press 1998 Medical Research Council Lung Cancer

Working Party Br J Cancer 1992)

ndash Mostly total dose of around 20 Gy (multiple fractions) or 8 Gy

single fraction recommended

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 55

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Van Lonkhuijzen

Radiother Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 56

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gynaecologic tumours

bull Cf review van Lonkhuijzen Radiother Oncol 2011

bull Consider intracavitary HDR brachytherapy

Rectal cancer

bull Up to 85 control of rectal bleeding (Hoskin in Doyle et al Second Edition New York Oxford University Press 1998)

Kaposi sarcoma

bull Good palliation for pain bleeding or edema TD 15-40 Gy SD 2 Gy gt90 response 70 complete remission (Review Becker et al Onkologie 2006)

Skin tumours (Miller in Doyle Oxford Textbook of Palliative Medicine New York Oxford University Press 1993)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 57

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duration of treatment effect

Lung cancer

bull Median duration of palliation 50 of remaining life span (30 Gy10d

27 Gy6d 17 Gy2 fract1w apart) (Medical Research Council Br J

Cancer 1991)

bull 1 fract 10 Gy vs 2 fract 85 Gy more patients need repeat RT (Medical Research Council Lung Cancer Working Party Br J Cancer 1992)

bull 417 pat need repeat RT within 3 m after 1x10 Gy (Scolaro Radiol

Med 1995)

Rec ovarian cancer

bull Median duration of palliation 4 m in 90 of patients until death (Corn Cancer 1994)

Cervical endometrial cancer

bull In 50 of patients pall Effect until death with 1-2x10 Gy

ndash Halle IJROBP 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 58

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull RT effective for improvement of

ndashThoracic symptoms (haemoptysis cough thoracic pain

dyspnoea airway obstruction) (Sirzeacuten Acta Oncol 2003 and others)

ndashQOL in about 13 of patients (Langendijk IJROBP 2000)

RT schedules

bull Systematic review (Fairchild JCO 264001-4011 2008)

ndash13 randomized trials 3473 patients

ndashdifferent RT schedules

ndashAim find optimal RT schedule for maximal palliation with

minimal toxicityneed for reirradiation

Thoracic symptoms

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 59

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz

Cancer

2007

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz Chow Hartsell Konski Cancer 2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 61

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemoptysis

bull Fig2 toux

733 689

812 802

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 62

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig3 doul thor 321 279

535 482

Cough

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 63

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 4 overall symptom burden

575 519

648 638

Thoracic pain

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 64

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 5 survie 1a

Cutoff (sensitivity analysis) BED[10] 35Gy vs LD

100 162

555 609

Overall symptom burden

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 65

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cutoff BED[10] 35Gy vs LD

265 217

Overall survival at 1y

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 66

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 7 Tox dysphagie

Cutoff BED[10] 30Gy vs LD

205 149

about x 2

Toxicity (dysphagia)

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 67

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomized trial 250 patients (Falk BMJ 2002)

bull Locally advanced non resectable NSCLC with minimal thoracic symptoms

bull Immediate vs delayed RT (at symptom onset)

bull In delayed arm 56 of patients died without RT

bull No difference in QOL odr OS

bull More acute toxicity in immediate RT arm

Randomized trial (Sundstrom Radiother Oncol 2005)

bull Advanced NSCLC

bull 2 RT schedules (5x4Gy vs 2x85 Gy) immediate RT

bull Stratification according to presenceabsence of thoracic symptoms

bull In asymptomatic patients no long term symptom control but important dysphagia

Timing

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 68

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull in 97 malignant

bull in 5-10 of lung cancer patients

bull Histology (exclude benign disease RT-chemosensible tumours

bull Generally spontanous improvement of symptoms by formation of collaterals

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 69

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Treatment

1 symptomatic

bull steroids

bull diuretics

bull Elevation of headthorax

2 causal bull chemotherapy (SCLC

lymphomas germinal tumours)

bull Endovascular stent placement

bull radiotherapy Palliative care in lung cancer ACCP

evidence- based clinical practice guidelines

(2nd edition)

Kvale Chest 2007

Superior vena cava syndrome

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

Radiotherapy

bull Mostly clinical response within 72 h

bull Complete clinical response at 2 w in 78 of patients with SCLC

and 63 of patients with NSCLC

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 72

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Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

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Duhamel Atlas clinique des maladies

des voies aeacuteriennes Elsevier

wwwupmccancercenterscom

Endobronchial brachytherapy

Cochrane analysis (Cardona The Cochrane

Library 2008)

bull No improved

symptom relief by

addition of

endobronchial

brachytherapy to

EBRT

bull Indicated in selected

patients pretreated

by EBRT with

central

endobronchial

obstruction

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 74

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Ozkok Lung Cancer 2008

Endobronchial brachytherapy

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Take home lung cancer

Dosefractionation

bull Minimum 10x3 Gy 5xw or equivalent

ndash better symptom control and better overall survival

ndash But more toxicity

bull Short schedule for symptom control and limited toxicity

ndashPoor performance status limited life expectancy

Timing

bull RT at the moment of symptom onset

bull No place for bdquoprophylactic palliative RTldquo according to evidence based guidelines

ndashExceptions

bull Young patient good PS aim of local control

bull Imminent symptoms (superior vena cava syndrome central airway obstruction

Rodrigues Pract Rad Oncol 2011

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 80

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 82

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 83

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 84

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 90

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 98

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 99

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Scoccianti Radiother Oncol 2012

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 100

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 101

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 102

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 103

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 104

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 105

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemorrhage

bull Bleeding in 6-10 of patients with advanced

cancer (Pereira et al Topics in Palliative Care Vol 4 New York

Oxford University Press 2000)

bull haemoptysis

bull haematemesis

bull haematocheziamelaena

bull vaginal bleeding

bull haematuria

bull bleeding in ulcerated skin lesions

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 52

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Mechanisms of haemostatic radiotherapy

bull Sparse literature

bull Coagulation activationsup1

ndash Oxydative endothelial damage

ndash Activation of thrombocytes

ndash Activation of inflammation

bull Long term anti-angiogenetic

sup1 Hallahan et al Oncology (Huntingt) 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 53

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Prostate cancer

bull Reduction of pain and bleeding in hormone refractory

prostate cancer (Kynaston Br J Urol 1990 Kawakami Nippon

Hinyokika Gakkai Zasshi 1993 Kalapurakal Int J Radiat Oncol Biol Phys

2003)

bull 100 improvement in patients with important hematuria (Carlton J Urol 1972)

Bladder cancer (Srinivasan et al Clin Oncol (R Coll Radiol) 1994)

bull 17 Gy in 2 fractions3 days 59 clearance of hematuria

bull 45 Gy in 12 fractions26 days 16 clearance of

hematuria

bull Selection by performance status Palliation (pain and

hematuria) better with hypofractionated RT worse

survival

bull No important side effects

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 54

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung cancer

bull Control of hemoptysis in up to 80 of patients (Brundage

Can J Oncol 1996 Medical Research Council Lung Cancer Working Party

Br J Cancer 1992 Hoskin in Doyle et al Second Edition New York

Oxford University Press 1998 Langendijk Int J Radiat Oncol Biol Phys

2000)

bull Optimal dosefractionation

ndash Hypofractionated RT seems to be equally effective to multiple

fractions (Rees Clin Oncol (R Coll Radiol) 1997 Sundstrom JCO

2004 Phase III Stevens Australas Radiol 1995 Phase III studies of

the MRC (s above)

ndash 10 Gy Single fraction equally effective to multiple fractions less

toxic (Hoskin in Doyle et al Second Edition New York Oxford

University Press 1998 Medical Research Council Lung Cancer

Working Party Br J Cancer 1992)

ndash Mostly total dose of around 20 Gy (multiple fractions) or 8 Gy

single fraction recommended

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 55

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Van Lonkhuijzen

Radiother Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 56

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gynaecologic tumours

bull Cf review van Lonkhuijzen Radiother Oncol 2011

bull Consider intracavitary HDR brachytherapy

Rectal cancer

bull Up to 85 control of rectal bleeding (Hoskin in Doyle et al Second Edition New York Oxford University Press 1998)

Kaposi sarcoma

bull Good palliation for pain bleeding or edema TD 15-40 Gy SD 2 Gy gt90 response 70 complete remission (Review Becker et al Onkologie 2006)

Skin tumours (Miller in Doyle Oxford Textbook of Palliative Medicine New York Oxford University Press 1993)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 57

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duration of treatment effect

Lung cancer

bull Median duration of palliation 50 of remaining life span (30 Gy10d

27 Gy6d 17 Gy2 fract1w apart) (Medical Research Council Br J

Cancer 1991)

bull 1 fract 10 Gy vs 2 fract 85 Gy more patients need repeat RT (Medical Research Council Lung Cancer Working Party Br J Cancer 1992)

bull 417 pat need repeat RT within 3 m after 1x10 Gy (Scolaro Radiol

Med 1995)

Rec ovarian cancer

bull Median duration of palliation 4 m in 90 of patients until death (Corn Cancer 1994)

Cervical endometrial cancer

bull In 50 of patients pall Effect until death with 1-2x10 Gy

ndash Halle IJROBP 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 58

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull RT effective for improvement of

ndashThoracic symptoms (haemoptysis cough thoracic pain

dyspnoea airway obstruction) (Sirzeacuten Acta Oncol 2003 and others)

ndashQOL in about 13 of patients (Langendijk IJROBP 2000)

RT schedules

bull Systematic review (Fairchild JCO 264001-4011 2008)

ndash13 randomized trials 3473 patients

ndashdifferent RT schedules

ndashAim find optimal RT schedule for maximal palliation with

minimal toxicityneed for reirradiation

Thoracic symptoms

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 59

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz

Cancer

2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 60

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz Chow Hartsell Konski Cancer 2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 61

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemoptysis

bull Fig2 toux

733 689

812 802

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 62

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig3 doul thor 321 279

535 482

Cough

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 63

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 4 overall symptom burden

575 519

648 638

Thoracic pain

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 64

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 5 survie 1a

Cutoff (sensitivity analysis) BED[10] 35Gy vs LD

100 162

555 609

Overall symptom burden

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 65

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cutoff BED[10] 35Gy vs LD

265 217

Overall survival at 1y

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 66

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 7 Tox dysphagie

Cutoff BED[10] 30Gy vs LD

205 149

about x 2

Toxicity (dysphagia)

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 67

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomized trial 250 patients (Falk BMJ 2002)

bull Locally advanced non resectable NSCLC with minimal thoracic symptoms

bull Immediate vs delayed RT (at symptom onset)

bull In delayed arm 56 of patients died without RT

bull No difference in QOL odr OS

bull More acute toxicity in immediate RT arm

Randomized trial (Sundstrom Radiother Oncol 2005)

bull Advanced NSCLC

bull 2 RT schedules (5x4Gy vs 2x85 Gy) immediate RT

bull Stratification according to presenceabsence of thoracic symptoms

bull In asymptomatic patients no long term symptom control but important dysphagia

Timing

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 68

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull in 97 malignant

bull in 5-10 of lung cancer patients

bull Histology (exclude benign disease RT-chemosensible tumours

bull Generally spontanous improvement of symptoms by formation of collaterals

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 69

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Treatment

1 symptomatic

bull steroids

bull diuretics

bull Elevation of headthorax

2 causal bull chemotherapy (SCLC

lymphomas germinal tumours)

bull Endovascular stent placement

bull radiotherapy Palliative care in lung cancer ACCP

evidence- based clinical practice guidelines

(2nd edition)

Kvale Chest 2007

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 70

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

Radiotherapy

bull Mostly clinical response within 72 h

bull Complete clinical response at 2 w in 78 of patients with SCLC

and 63 of patients with NSCLC

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 71

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 72

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 73

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duhamel Atlas clinique des maladies

des voies aeacuteriennes Elsevier

wwwupmccancercenterscom

Endobronchial brachytherapy

Cochrane analysis (Cardona The Cochrane

Library 2008)

bull No improved

symptom relief by

addition of

endobronchial

brachytherapy to

EBRT

bull Indicated in selected

patients pretreated

by EBRT with

central

endobronchial

obstruction

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 74

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Ozkok Lung Cancer 2008

Endobronchial brachytherapy

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 75

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Take home lung cancer

Dosefractionation

bull Minimum 10x3 Gy 5xw or equivalent

ndash better symptom control and better overall survival

ndash But more toxicity

bull Short schedule for symptom control and limited toxicity

ndashPoor performance status limited life expectancy

Timing

bull RT at the moment of symptom onset

bull No place for bdquoprophylactic palliative RTldquo according to evidence based guidelines

ndashExceptions

bull Young patient good PS aim of local control

bull Imminent symptoms (superior vena cava syndrome central airway obstruction

Rodrigues Pract Rad Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 76

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 77

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 78

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 80

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 81

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 82

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 83

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 84

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 85

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 90

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 98

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 99

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Scoccianti Radiother Oncol 2012

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 100

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 101

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 102

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 103

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 104

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 105

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 106

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Page 52: SRO Tutorial Palliative Care 04.05.2012 Palliative Radiotherapy · 2018-02-22 · SRO Tutorial Palliative Care – Palliative Radiotherapy 30 Jacqueline Vock, Universitätsklinik

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 52

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Mechanisms of haemostatic radiotherapy

bull Sparse literature

bull Coagulation activationsup1

ndash Oxydative endothelial damage

ndash Activation of thrombocytes

ndash Activation of inflammation

bull Long term anti-angiogenetic

sup1 Hallahan et al Oncology (Huntingt) 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 53

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Prostate cancer

bull Reduction of pain and bleeding in hormone refractory

prostate cancer (Kynaston Br J Urol 1990 Kawakami Nippon

Hinyokika Gakkai Zasshi 1993 Kalapurakal Int J Radiat Oncol Biol Phys

2003)

bull 100 improvement in patients with important hematuria (Carlton J Urol 1972)

Bladder cancer (Srinivasan et al Clin Oncol (R Coll Radiol) 1994)

bull 17 Gy in 2 fractions3 days 59 clearance of hematuria

bull 45 Gy in 12 fractions26 days 16 clearance of

hematuria

bull Selection by performance status Palliation (pain and

hematuria) better with hypofractionated RT worse

survival

bull No important side effects

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 54

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung cancer

bull Control of hemoptysis in up to 80 of patients (Brundage

Can J Oncol 1996 Medical Research Council Lung Cancer Working Party

Br J Cancer 1992 Hoskin in Doyle et al Second Edition New York

Oxford University Press 1998 Langendijk Int J Radiat Oncol Biol Phys

2000)

bull Optimal dosefractionation

ndash Hypofractionated RT seems to be equally effective to multiple

fractions (Rees Clin Oncol (R Coll Radiol) 1997 Sundstrom JCO

2004 Phase III Stevens Australas Radiol 1995 Phase III studies of

the MRC (s above)

ndash 10 Gy Single fraction equally effective to multiple fractions less

toxic (Hoskin in Doyle et al Second Edition New York Oxford

University Press 1998 Medical Research Council Lung Cancer

Working Party Br J Cancer 1992)

ndash Mostly total dose of around 20 Gy (multiple fractions) or 8 Gy

single fraction recommended

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 55

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Van Lonkhuijzen

Radiother Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 56

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gynaecologic tumours

bull Cf review van Lonkhuijzen Radiother Oncol 2011

bull Consider intracavitary HDR brachytherapy

Rectal cancer

bull Up to 85 control of rectal bleeding (Hoskin in Doyle et al Second Edition New York Oxford University Press 1998)

Kaposi sarcoma

bull Good palliation for pain bleeding or edema TD 15-40 Gy SD 2 Gy gt90 response 70 complete remission (Review Becker et al Onkologie 2006)

Skin tumours (Miller in Doyle Oxford Textbook of Palliative Medicine New York Oxford University Press 1993)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 57

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duration of treatment effect

Lung cancer

bull Median duration of palliation 50 of remaining life span (30 Gy10d

27 Gy6d 17 Gy2 fract1w apart) (Medical Research Council Br J

Cancer 1991)

bull 1 fract 10 Gy vs 2 fract 85 Gy more patients need repeat RT (Medical Research Council Lung Cancer Working Party Br J Cancer 1992)

bull 417 pat need repeat RT within 3 m after 1x10 Gy (Scolaro Radiol

Med 1995)

Rec ovarian cancer

bull Median duration of palliation 4 m in 90 of patients until death (Corn Cancer 1994)

Cervical endometrial cancer

bull In 50 of patients pall Effect until death with 1-2x10 Gy

ndash Halle IJROBP 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 58

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull RT effective for improvement of

ndashThoracic symptoms (haemoptysis cough thoracic pain

dyspnoea airway obstruction) (Sirzeacuten Acta Oncol 2003 and others)

ndashQOL in about 13 of patients (Langendijk IJROBP 2000)

RT schedules

bull Systematic review (Fairchild JCO 264001-4011 2008)

ndash13 randomized trials 3473 patients

ndashdifferent RT schedules

ndashAim find optimal RT schedule for maximal palliation with

minimal toxicityneed for reirradiation

Thoracic symptoms

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 59

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz

Cancer

2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 60

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz Chow Hartsell Konski Cancer 2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 61

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemoptysis

bull Fig2 toux

733 689

812 802

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 62

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig3 doul thor 321 279

535 482

Cough

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 63

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 4 overall symptom burden

575 519

648 638

Thoracic pain

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 64

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 5 survie 1a

Cutoff (sensitivity analysis) BED[10] 35Gy vs LD

100 162

555 609

Overall symptom burden

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 65

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cutoff BED[10] 35Gy vs LD

265 217

Overall survival at 1y

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 66

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 7 Tox dysphagie

Cutoff BED[10] 30Gy vs LD

205 149

about x 2

Toxicity (dysphagia)

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 67

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomized trial 250 patients (Falk BMJ 2002)

bull Locally advanced non resectable NSCLC with minimal thoracic symptoms

bull Immediate vs delayed RT (at symptom onset)

bull In delayed arm 56 of patients died without RT

bull No difference in QOL odr OS

bull More acute toxicity in immediate RT arm

Randomized trial (Sundstrom Radiother Oncol 2005)

bull Advanced NSCLC

bull 2 RT schedules (5x4Gy vs 2x85 Gy) immediate RT

bull Stratification according to presenceabsence of thoracic symptoms

bull In asymptomatic patients no long term symptom control but important dysphagia

Timing

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 68

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull in 97 malignant

bull in 5-10 of lung cancer patients

bull Histology (exclude benign disease RT-chemosensible tumours

bull Generally spontanous improvement of symptoms by formation of collaterals

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 69

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Treatment

1 symptomatic

bull steroids

bull diuretics

bull Elevation of headthorax

2 causal bull chemotherapy (SCLC

lymphomas germinal tumours)

bull Endovascular stent placement

bull radiotherapy Palliative care in lung cancer ACCP

evidence- based clinical practice guidelines

(2nd edition)

Kvale Chest 2007

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 70

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

Radiotherapy

bull Mostly clinical response within 72 h

bull Complete clinical response at 2 w in 78 of patients with SCLC

and 63 of patients with NSCLC

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 71

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 72

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 73

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duhamel Atlas clinique des maladies

des voies aeacuteriennes Elsevier

wwwupmccancercenterscom

Endobronchial brachytherapy

Cochrane analysis (Cardona The Cochrane

Library 2008)

bull No improved

symptom relief by

addition of

endobronchial

brachytherapy to

EBRT

bull Indicated in selected

patients pretreated

by EBRT with

central

endobronchial

obstruction

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 74

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Ozkok Lung Cancer 2008

Endobronchial brachytherapy

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 75

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Take home lung cancer

Dosefractionation

bull Minimum 10x3 Gy 5xw or equivalent

ndash better symptom control and better overall survival

ndash But more toxicity

bull Short schedule for symptom control and limited toxicity

ndashPoor performance status limited life expectancy

Timing

bull RT at the moment of symptom onset

bull No place for bdquoprophylactic palliative RTldquo according to evidence based guidelines

ndashExceptions

bull Young patient good PS aim of local control

bull Imminent symptoms (superior vena cava syndrome central airway obstruction

Rodrigues Pract Rad Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 76

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 77

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 78

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 80

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 81

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 82

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 83

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 84

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 85

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 90

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 99

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Scoccianti Radiother Oncol 2012

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 100

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 101

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 102

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 103

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 104

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Page 53: SRO Tutorial Palliative Care 04.05.2012 Palliative Radiotherapy · 2018-02-22 · SRO Tutorial Palliative Care – Palliative Radiotherapy 30 Jacqueline Vock, Universitätsklinik

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 53

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Prostate cancer

bull Reduction of pain and bleeding in hormone refractory

prostate cancer (Kynaston Br J Urol 1990 Kawakami Nippon

Hinyokika Gakkai Zasshi 1993 Kalapurakal Int J Radiat Oncol Biol Phys

2003)

bull 100 improvement in patients with important hematuria (Carlton J Urol 1972)

Bladder cancer (Srinivasan et al Clin Oncol (R Coll Radiol) 1994)

bull 17 Gy in 2 fractions3 days 59 clearance of hematuria

bull 45 Gy in 12 fractions26 days 16 clearance of

hematuria

bull Selection by performance status Palliation (pain and

hematuria) better with hypofractionated RT worse

survival

bull No important side effects

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 54

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung cancer

bull Control of hemoptysis in up to 80 of patients (Brundage

Can J Oncol 1996 Medical Research Council Lung Cancer Working Party

Br J Cancer 1992 Hoskin in Doyle et al Second Edition New York

Oxford University Press 1998 Langendijk Int J Radiat Oncol Biol Phys

2000)

bull Optimal dosefractionation

ndash Hypofractionated RT seems to be equally effective to multiple

fractions (Rees Clin Oncol (R Coll Radiol) 1997 Sundstrom JCO

2004 Phase III Stevens Australas Radiol 1995 Phase III studies of

the MRC (s above)

ndash 10 Gy Single fraction equally effective to multiple fractions less

toxic (Hoskin in Doyle et al Second Edition New York Oxford

University Press 1998 Medical Research Council Lung Cancer

Working Party Br J Cancer 1992)

ndash Mostly total dose of around 20 Gy (multiple fractions) or 8 Gy

single fraction recommended

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 55

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Van Lonkhuijzen

Radiother Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 56

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gynaecologic tumours

bull Cf review van Lonkhuijzen Radiother Oncol 2011

bull Consider intracavitary HDR brachytherapy

Rectal cancer

bull Up to 85 control of rectal bleeding (Hoskin in Doyle et al Second Edition New York Oxford University Press 1998)

Kaposi sarcoma

bull Good palliation for pain bleeding or edema TD 15-40 Gy SD 2 Gy gt90 response 70 complete remission (Review Becker et al Onkologie 2006)

Skin tumours (Miller in Doyle Oxford Textbook of Palliative Medicine New York Oxford University Press 1993)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 57

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duration of treatment effect

Lung cancer

bull Median duration of palliation 50 of remaining life span (30 Gy10d

27 Gy6d 17 Gy2 fract1w apart) (Medical Research Council Br J

Cancer 1991)

bull 1 fract 10 Gy vs 2 fract 85 Gy more patients need repeat RT (Medical Research Council Lung Cancer Working Party Br J Cancer 1992)

bull 417 pat need repeat RT within 3 m after 1x10 Gy (Scolaro Radiol

Med 1995)

Rec ovarian cancer

bull Median duration of palliation 4 m in 90 of patients until death (Corn Cancer 1994)

Cervical endometrial cancer

bull In 50 of patients pall Effect until death with 1-2x10 Gy

ndash Halle IJROBP 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 58

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull RT effective for improvement of

ndashThoracic symptoms (haemoptysis cough thoracic pain

dyspnoea airway obstruction) (Sirzeacuten Acta Oncol 2003 and others)

ndashQOL in about 13 of patients (Langendijk IJROBP 2000)

RT schedules

bull Systematic review (Fairchild JCO 264001-4011 2008)

ndash13 randomized trials 3473 patients

ndashdifferent RT schedules

ndashAim find optimal RT schedule for maximal palliation with

minimal toxicityneed for reirradiation

Thoracic symptoms

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 59

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz

Cancer

2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 60

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz Chow Hartsell Konski Cancer 2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 61

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemoptysis

bull Fig2 toux

733 689

812 802

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 62

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig3 doul thor 321 279

535 482

Cough

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 63

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 4 overall symptom burden

575 519

648 638

Thoracic pain

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 64

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 5 survie 1a

Cutoff (sensitivity analysis) BED[10] 35Gy vs LD

100 162

555 609

Overall symptom burden

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 65

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cutoff BED[10] 35Gy vs LD

265 217

Overall survival at 1y

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 66

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 7 Tox dysphagie

Cutoff BED[10] 30Gy vs LD

205 149

about x 2

Toxicity (dysphagia)

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 67

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomized trial 250 patients (Falk BMJ 2002)

bull Locally advanced non resectable NSCLC with minimal thoracic symptoms

bull Immediate vs delayed RT (at symptom onset)

bull In delayed arm 56 of patients died without RT

bull No difference in QOL odr OS

bull More acute toxicity in immediate RT arm

Randomized trial (Sundstrom Radiother Oncol 2005)

bull Advanced NSCLC

bull 2 RT schedules (5x4Gy vs 2x85 Gy) immediate RT

bull Stratification according to presenceabsence of thoracic symptoms

bull In asymptomatic patients no long term symptom control but important dysphagia

Timing

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 68

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull in 97 malignant

bull in 5-10 of lung cancer patients

bull Histology (exclude benign disease RT-chemosensible tumours

bull Generally spontanous improvement of symptoms by formation of collaterals

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 69

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Treatment

1 symptomatic

bull steroids

bull diuretics

bull Elevation of headthorax

2 causal bull chemotherapy (SCLC

lymphomas germinal tumours)

bull Endovascular stent placement

bull radiotherapy Palliative care in lung cancer ACCP

evidence- based clinical practice guidelines

(2nd edition)

Kvale Chest 2007

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 70

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

Radiotherapy

bull Mostly clinical response within 72 h

bull Complete clinical response at 2 w in 78 of patients with SCLC

and 63 of patients with NSCLC

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 71

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 72

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 73

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duhamel Atlas clinique des maladies

des voies aeacuteriennes Elsevier

wwwupmccancercenterscom

Endobronchial brachytherapy

Cochrane analysis (Cardona The Cochrane

Library 2008)

bull No improved

symptom relief by

addition of

endobronchial

brachytherapy to

EBRT

bull Indicated in selected

patients pretreated

by EBRT with

central

endobronchial

obstruction

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 74

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Ozkok Lung Cancer 2008

Endobronchial brachytherapy

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 75

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Take home lung cancer

Dosefractionation

bull Minimum 10x3 Gy 5xw or equivalent

ndash better symptom control and better overall survival

ndash But more toxicity

bull Short schedule for symptom control and limited toxicity

ndashPoor performance status limited life expectancy

Timing

bull RT at the moment of symptom onset

bull No place for bdquoprophylactic palliative RTldquo according to evidence based guidelines

ndashExceptions

bull Young patient good PS aim of local control

bull Imminent symptoms (superior vena cava syndrome central airway obstruction

Rodrigues Pract Rad Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 76

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 77

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 78

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 80

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 81

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 82

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 83

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 84

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 85

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 90

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 98

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 99

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Scoccianti Radiother Oncol 2012

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 100

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 101

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 102

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 103

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 104

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 105

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Page 54: SRO Tutorial Palliative Care 04.05.2012 Palliative Radiotherapy · 2018-02-22 · SRO Tutorial Palliative Care – Palliative Radiotherapy 30 Jacqueline Vock, Universitätsklinik

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 54

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung cancer

bull Control of hemoptysis in up to 80 of patients (Brundage

Can J Oncol 1996 Medical Research Council Lung Cancer Working Party

Br J Cancer 1992 Hoskin in Doyle et al Second Edition New York

Oxford University Press 1998 Langendijk Int J Radiat Oncol Biol Phys

2000)

bull Optimal dosefractionation

ndash Hypofractionated RT seems to be equally effective to multiple

fractions (Rees Clin Oncol (R Coll Radiol) 1997 Sundstrom JCO

2004 Phase III Stevens Australas Radiol 1995 Phase III studies of

the MRC (s above)

ndash 10 Gy Single fraction equally effective to multiple fractions less

toxic (Hoskin in Doyle et al Second Edition New York Oxford

University Press 1998 Medical Research Council Lung Cancer

Working Party Br J Cancer 1992)

ndash Mostly total dose of around 20 Gy (multiple fractions) or 8 Gy

single fraction recommended

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 55

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Van Lonkhuijzen

Radiother Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 56

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gynaecologic tumours

bull Cf review van Lonkhuijzen Radiother Oncol 2011

bull Consider intracavitary HDR brachytherapy

Rectal cancer

bull Up to 85 control of rectal bleeding (Hoskin in Doyle et al Second Edition New York Oxford University Press 1998)

Kaposi sarcoma

bull Good palliation for pain bleeding or edema TD 15-40 Gy SD 2 Gy gt90 response 70 complete remission (Review Becker et al Onkologie 2006)

Skin tumours (Miller in Doyle Oxford Textbook of Palliative Medicine New York Oxford University Press 1993)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 57

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duration of treatment effect

Lung cancer

bull Median duration of palliation 50 of remaining life span (30 Gy10d

27 Gy6d 17 Gy2 fract1w apart) (Medical Research Council Br J

Cancer 1991)

bull 1 fract 10 Gy vs 2 fract 85 Gy more patients need repeat RT (Medical Research Council Lung Cancer Working Party Br J Cancer 1992)

bull 417 pat need repeat RT within 3 m after 1x10 Gy (Scolaro Radiol

Med 1995)

Rec ovarian cancer

bull Median duration of palliation 4 m in 90 of patients until death (Corn Cancer 1994)

Cervical endometrial cancer

bull In 50 of patients pall Effect until death with 1-2x10 Gy

ndash Halle IJROBP 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 58

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull RT effective for improvement of

ndashThoracic symptoms (haemoptysis cough thoracic pain

dyspnoea airway obstruction) (Sirzeacuten Acta Oncol 2003 and others)

ndashQOL in about 13 of patients (Langendijk IJROBP 2000)

RT schedules

bull Systematic review (Fairchild JCO 264001-4011 2008)

ndash13 randomized trials 3473 patients

ndashdifferent RT schedules

ndashAim find optimal RT schedule for maximal palliation with

minimal toxicityneed for reirradiation

Thoracic symptoms

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 59

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz

Cancer

2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 60

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz Chow Hartsell Konski Cancer 2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 61

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemoptysis

bull Fig2 toux

733 689

812 802

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 62

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig3 doul thor 321 279

535 482

Cough

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 63

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 4 overall symptom burden

575 519

648 638

Thoracic pain

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 64

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 5 survie 1a

Cutoff (sensitivity analysis) BED[10] 35Gy vs LD

100 162

555 609

Overall symptom burden

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 65

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cutoff BED[10] 35Gy vs LD

265 217

Overall survival at 1y

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 66

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 7 Tox dysphagie

Cutoff BED[10] 30Gy vs LD

205 149

about x 2

Toxicity (dysphagia)

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 67

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomized trial 250 patients (Falk BMJ 2002)

bull Locally advanced non resectable NSCLC with minimal thoracic symptoms

bull Immediate vs delayed RT (at symptom onset)

bull In delayed arm 56 of patients died without RT

bull No difference in QOL odr OS

bull More acute toxicity in immediate RT arm

Randomized trial (Sundstrom Radiother Oncol 2005)

bull Advanced NSCLC

bull 2 RT schedules (5x4Gy vs 2x85 Gy) immediate RT

bull Stratification according to presenceabsence of thoracic symptoms

bull In asymptomatic patients no long term symptom control but important dysphagia

Timing

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 68

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull in 97 malignant

bull in 5-10 of lung cancer patients

bull Histology (exclude benign disease RT-chemosensible tumours

bull Generally spontanous improvement of symptoms by formation of collaterals

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 69

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Treatment

1 symptomatic

bull steroids

bull diuretics

bull Elevation of headthorax

2 causal bull chemotherapy (SCLC

lymphomas germinal tumours)

bull Endovascular stent placement

bull radiotherapy Palliative care in lung cancer ACCP

evidence- based clinical practice guidelines

(2nd edition)

Kvale Chest 2007

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 70

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

Radiotherapy

bull Mostly clinical response within 72 h

bull Complete clinical response at 2 w in 78 of patients with SCLC

and 63 of patients with NSCLC

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 71

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 72

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 73

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duhamel Atlas clinique des maladies

des voies aeacuteriennes Elsevier

wwwupmccancercenterscom

Endobronchial brachytherapy

Cochrane analysis (Cardona The Cochrane

Library 2008)

bull No improved

symptom relief by

addition of

endobronchial

brachytherapy to

EBRT

bull Indicated in selected

patients pretreated

by EBRT with

central

endobronchial

obstruction

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 74

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Ozkok Lung Cancer 2008

Endobronchial brachytherapy

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 75

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Take home lung cancer

Dosefractionation

bull Minimum 10x3 Gy 5xw or equivalent

ndash better symptom control and better overall survival

ndash But more toxicity

bull Short schedule for symptom control and limited toxicity

ndashPoor performance status limited life expectancy

Timing

bull RT at the moment of symptom onset

bull No place for bdquoprophylactic palliative RTldquo according to evidence based guidelines

ndashExceptions

bull Young patient good PS aim of local control

bull Imminent symptoms (superior vena cava syndrome central airway obstruction

Rodrigues Pract Rad Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 76

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 77

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 78

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 80

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 81

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 82

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 83

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 84

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 85

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 90

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 98

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 99

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Scoccianti Radiother Oncol 2012

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 100

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 101

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 102

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 103

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 104

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 105

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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SRO Tutorial Palliative Care ndash Palliative Radiotherapy 55

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Van Lonkhuijzen

Radiother Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 56

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gynaecologic tumours

bull Cf review van Lonkhuijzen Radiother Oncol 2011

bull Consider intracavitary HDR brachytherapy

Rectal cancer

bull Up to 85 control of rectal bleeding (Hoskin in Doyle et al Second Edition New York Oxford University Press 1998)

Kaposi sarcoma

bull Good palliation for pain bleeding or edema TD 15-40 Gy SD 2 Gy gt90 response 70 complete remission (Review Becker et al Onkologie 2006)

Skin tumours (Miller in Doyle Oxford Textbook of Palliative Medicine New York Oxford University Press 1993)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 57

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duration of treatment effect

Lung cancer

bull Median duration of palliation 50 of remaining life span (30 Gy10d

27 Gy6d 17 Gy2 fract1w apart) (Medical Research Council Br J

Cancer 1991)

bull 1 fract 10 Gy vs 2 fract 85 Gy more patients need repeat RT (Medical Research Council Lung Cancer Working Party Br J Cancer 1992)

bull 417 pat need repeat RT within 3 m after 1x10 Gy (Scolaro Radiol

Med 1995)

Rec ovarian cancer

bull Median duration of palliation 4 m in 90 of patients until death (Corn Cancer 1994)

Cervical endometrial cancer

bull In 50 of patients pall Effect until death with 1-2x10 Gy

ndash Halle IJROBP 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 58

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull RT effective for improvement of

ndashThoracic symptoms (haemoptysis cough thoracic pain

dyspnoea airway obstruction) (Sirzeacuten Acta Oncol 2003 and others)

ndashQOL in about 13 of patients (Langendijk IJROBP 2000)

RT schedules

bull Systematic review (Fairchild JCO 264001-4011 2008)

ndash13 randomized trials 3473 patients

ndashdifferent RT schedules

ndashAim find optimal RT schedule for maximal palliation with

minimal toxicityneed for reirradiation

Thoracic symptoms

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 59

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz

Cancer

2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 60

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz Chow Hartsell Konski Cancer 2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 61

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemoptysis

bull Fig2 toux

733 689

812 802

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 62

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig3 doul thor 321 279

535 482

Cough

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 63

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 4 overall symptom burden

575 519

648 638

Thoracic pain

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 64

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 5 survie 1a

Cutoff (sensitivity analysis) BED[10] 35Gy vs LD

100 162

555 609

Overall symptom burden

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 65

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cutoff BED[10] 35Gy vs LD

265 217

Overall survival at 1y

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 66

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 7 Tox dysphagie

Cutoff BED[10] 30Gy vs LD

205 149

about x 2

Toxicity (dysphagia)

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 67

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomized trial 250 patients (Falk BMJ 2002)

bull Locally advanced non resectable NSCLC with minimal thoracic symptoms

bull Immediate vs delayed RT (at symptom onset)

bull In delayed arm 56 of patients died without RT

bull No difference in QOL odr OS

bull More acute toxicity in immediate RT arm

Randomized trial (Sundstrom Radiother Oncol 2005)

bull Advanced NSCLC

bull 2 RT schedules (5x4Gy vs 2x85 Gy) immediate RT

bull Stratification according to presenceabsence of thoracic symptoms

bull In asymptomatic patients no long term symptom control but important dysphagia

Timing

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 68

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull in 97 malignant

bull in 5-10 of lung cancer patients

bull Histology (exclude benign disease RT-chemosensible tumours

bull Generally spontanous improvement of symptoms by formation of collaterals

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 69

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Treatment

1 symptomatic

bull steroids

bull diuretics

bull Elevation of headthorax

2 causal bull chemotherapy (SCLC

lymphomas germinal tumours)

bull Endovascular stent placement

bull radiotherapy Palliative care in lung cancer ACCP

evidence- based clinical practice guidelines

(2nd edition)

Kvale Chest 2007

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 70

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

Radiotherapy

bull Mostly clinical response within 72 h

bull Complete clinical response at 2 w in 78 of patients with SCLC

and 63 of patients with NSCLC

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 71

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 72

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 73

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duhamel Atlas clinique des maladies

des voies aeacuteriennes Elsevier

wwwupmccancercenterscom

Endobronchial brachytherapy

Cochrane analysis (Cardona The Cochrane

Library 2008)

bull No improved

symptom relief by

addition of

endobronchial

brachytherapy to

EBRT

bull Indicated in selected

patients pretreated

by EBRT with

central

endobronchial

obstruction

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 74

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Ozkok Lung Cancer 2008

Endobronchial brachytherapy

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 75

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Take home lung cancer

Dosefractionation

bull Minimum 10x3 Gy 5xw or equivalent

ndash better symptom control and better overall survival

ndash But more toxicity

bull Short schedule for symptom control and limited toxicity

ndashPoor performance status limited life expectancy

Timing

bull RT at the moment of symptom onset

bull No place for bdquoprophylactic palliative RTldquo according to evidence based guidelines

ndashExceptions

bull Young patient good PS aim of local control

bull Imminent symptoms (superior vena cava syndrome central airway obstruction

Rodrigues Pract Rad Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 76

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 77

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 78

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 80

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 81

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 82

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 83

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 84

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 85

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 90

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 98

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 99

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Scoccianti Radiother Oncol 2012

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 100

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 101

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 102

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 103

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 104

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 105

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 106

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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SRO Tutorial Palliative Care ndash Palliative Radiotherapy 56

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gynaecologic tumours

bull Cf review van Lonkhuijzen Radiother Oncol 2011

bull Consider intracavitary HDR brachytherapy

Rectal cancer

bull Up to 85 control of rectal bleeding (Hoskin in Doyle et al Second Edition New York Oxford University Press 1998)

Kaposi sarcoma

bull Good palliation for pain bleeding or edema TD 15-40 Gy SD 2 Gy gt90 response 70 complete remission (Review Becker et al Onkologie 2006)

Skin tumours (Miller in Doyle Oxford Textbook of Palliative Medicine New York Oxford University Press 1993)

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 57

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duration of treatment effect

Lung cancer

bull Median duration of palliation 50 of remaining life span (30 Gy10d

27 Gy6d 17 Gy2 fract1w apart) (Medical Research Council Br J

Cancer 1991)

bull 1 fract 10 Gy vs 2 fract 85 Gy more patients need repeat RT (Medical Research Council Lung Cancer Working Party Br J Cancer 1992)

bull 417 pat need repeat RT within 3 m after 1x10 Gy (Scolaro Radiol

Med 1995)

Rec ovarian cancer

bull Median duration of palliation 4 m in 90 of patients until death (Corn Cancer 1994)

Cervical endometrial cancer

bull In 50 of patients pall Effect until death with 1-2x10 Gy

ndash Halle IJROBP 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 58

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull RT effective for improvement of

ndashThoracic symptoms (haemoptysis cough thoracic pain

dyspnoea airway obstruction) (Sirzeacuten Acta Oncol 2003 and others)

ndashQOL in about 13 of patients (Langendijk IJROBP 2000)

RT schedules

bull Systematic review (Fairchild JCO 264001-4011 2008)

ndash13 randomized trials 3473 patients

ndashdifferent RT schedules

ndashAim find optimal RT schedule for maximal palliation with

minimal toxicityneed for reirradiation

Thoracic symptoms

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 59

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz

Cancer

2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 60

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz Chow Hartsell Konski Cancer 2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 61

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemoptysis

bull Fig2 toux

733 689

812 802

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 62

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig3 doul thor 321 279

535 482

Cough

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 63

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 4 overall symptom burden

575 519

648 638

Thoracic pain

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 64

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 5 survie 1a

Cutoff (sensitivity analysis) BED[10] 35Gy vs LD

100 162

555 609

Overall symptom burden

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 65

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cutoff BED[10] 35Gy vs LD

265 217

Overall survival at 1y

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 66

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 7 Tox dysphagie

Cutoff BED[10] 30Gy vs LD

205 149

about x 2

Toxicity (dysphagia)

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 67

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomized trial 250 patients (Falk BMJ 2002)

bull Locally advanced non resectable NSCLC with minimal thoracic symptoms

bull Immediate vs delayed RT (at symptom onset)

bull In delayed arm 56 of patients died without RT

bull No difference in QOL odr OS

bull More acute toxicity in immediate RT arm

Randomized trial (Sundstrom Radiother Oncol 2005)

bull Advanced NSCLC

bull 2 RT schedules (5x4Gy vs 2x85 Gy) immediate RT

bull Stratification according to presenceabsence of thoracic symptoms

bull In asymptomatic patients no long term symptom control but important dysphagia

Timing

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 68

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull in 97 malignant

bull in 5-10 of lung cancer patients

bull Histology (exclude benign disease RT-chemosensible tumours

bull Generally spontanous improvement of symptoms by formation of collaterals

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 69

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Treatment

1 symptomatic

bull steroids

bull diuretics

bull Elevation of headthorax

2 causal bull chemotherapy (SCLC

lymphomas germinal tumours)

bull Endovascular stent placement

bull radiotherapy Palliative care in lung cancer ACCP

evidence- based clinical practice guidelines

(2nd edition)

Kvale Chest 2007

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 70

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

Radiotherapy

bull Mostly clinical response within 72 h

bull Complete clinical response at 2 w in 78 of patients with SCLC

and 63 of patients with NSCLC

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 71

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 72

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 73

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duhamel Atlas clinique des maladies

des voies aeacuteriennes Elsevier

wwwupmccancercenterscom

Endobronchial brachytherapy

Cochrane analysis (Cardona The Cochrane

Library 2008)

bull No improved

symptom relief by

addition of

endobronchial

brachytherapy to

EBRT

bull Indicated in selected

patients pretreated

by EBRT with

central

endobronchial

obstruction

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 74

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Ozkok Lung Cancer 2008

Endobronchial brachytherapy

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 75

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Take home lung cancer

Dosefractionation

bull Minimum 10x3 Gy 5xw or equivalent

ndash better symptom control and better overall survival

ndash But more toxicity

bull Short schedule for symptom control and limited toxicity

ndashPoor performance status limited life expectancy

Timing

bull RT at the moment of symptom onset

bull No place for bdquoprophylactic palliative RTldquo according to evidence based guidelines

ndashExceptions

bull Young patient good PS aim of local control

bull Imminent symptoms (superior vena cava syndrome central airway obstruction

Rodrigues Pract Rad Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 76

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 77

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 78

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 80

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 81

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 82

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 83

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 84

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 85

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 90

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 98

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 99

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Scoccianti Radiother Oncol 2012

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 100

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 101

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 102

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 103

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 104

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 105

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 106

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Page 57: SRO Tutorial Palliative Care 04.05.2012 Palliative Radiotherapy · 2018-02-22 · SRO Tutorial Palliative Care – Palliative Radiotherapy 30 Jacqueline Vock, Universitätsklinik

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 57

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duration of treatment effect

Lung cancer

bull Median duration of palliation 50 of remaining life span (30 Gy10d

27 Gy6d 17 Gy2 fract1w apart) (Medical Research Council Br J

Cancer 1991)

bull 1 fract 10 Gy vs 2 fract 85 Gy more patients need repeat RT (Medical Research Council Lung Cancer Working Party Br J Cancer 1992)

bull 417 pat need repeat RT within 3 m after 1x10 Gy (Scolaro Radiol

Med 1995)

Rec ovarian cancer

bull Median duration of palliation 4 m in 90 of patients until death (Corn Cancer 1994)

Cervical endometrial cancer

bull In 50 of patients pall Effect until death with 1-2x10 Gy

ndash Halle IJROBP 1986

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 58

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull RT effective for improvement of

ndashThoracic symptoms (haemoptysis cough thoracic pain

dyspnoea airway obstruction) (Sirzeacuten Acta Oncol 2003 and others)

ndashQOL in about 13 of patients (Langendijk IJROBP 2000)

RT schedules

bull Systematic review (Fairchild JCO 264001-4011 2008)

ndash13 randomized trials 3473 patients

ndashdifferent RT schedules

ndashAim find optimal RT schedule for maximal palliation with

minimal toxicityneed for reirradiation

Thoracic symptoms

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 59

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz

Cancer

2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 60

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz Chow Hartsell Konski Cancer 2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 61

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemoptysis

bull Fig2 toux

733 689

812 802

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 62

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig3 doul thor 321 279

535 482

Cough

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 63

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 4 overall symptom burden

575 519

648 638

Thoracic pain

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 64

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 5 survie 1a

Cutoff (sensitivity analysis) BED[10] 35Gy vs LD

100 162

555 609

Overall symptom burden

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 65

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cutoff BED[10] 35Gy vs LD

265 217

Overall survival at 1y

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 66

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 7 Tox dysphagie

Cutoff BED[10] 30Gy vs LD

205 149

about x 2

Toxicity (dysphagia)

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 67

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomized trial 250 patients (Falk BMJ 2002)

bull Locally advanced non resectable NSCLC with minimal thoracic symptoms

bull Immediate vs delayed RT (at symptom onset)

bull In delayed arm 56 of patients died without RT

bull No difference in QOL odr OS

bull More acute toxicity in immediate RT arm

Randomized trial (Sundstrom Radiother Oncol 2005)

bull Advanced NSCLC

bull 2 RT schedules (5x4Gy vs 2x85 Gy) immediate RT

bull Stratification according to presenceabsence of thoracic symptoms

bull In asymptomatic patients no long term symptom control but important dysphagia

Timing

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 68

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull in 97 malignant

bull in 5-10 of lung cancer patients

bull Histology (exclude benign disease RT-chemosensible tumours

bull Generally spontanous improvement of symptoms by formation of collaterals

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 69

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Treatment

1 symptomatic

bull steroids

bull diuretics

bull Elevation of headthorax

2 causal bull chemotherapy (SCLC

lymphomas germinal tumours)

bull Endovascular stent placement

bull radiotherapy Palliative care in lung cancer ACCP

evidence- based clinical practice guidelines

(2nd edition)

Kvale Chest 2007

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 70

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

Radiotherapy

bull Mostly clinical response within 72 h

bull Complete clinical response at 2 w in 78 of patients with SCLC

and 63 of patients with NSCLC

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 71

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 72

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 73

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duhamel Atlas clinique des maladies

des voies aeacuteriennes Elsevier

wwwupmccancercenterscom

Endobronchial brachytherapy

Cochrane analysis (Cardona The Cochrane

Library 2008)

bull No improved

symptom relief by

addition of

endobronchial

brachytherapy to

EBRT

bull Indicated in selected

patients pretreated

by EBRT with

central

endobronchial

obstruction

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 74

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Ozkok Lung Cancer 2008

Endobronchial brachytherapy

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 75

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Take home lung cancer

Dosefractionation

bull Minimum 10x3 Gy 5xw or equivalent

ndash better symptom control and better overall survival

ndash But more toxicity

bull Short schedule for symptom control and limited toxicity

ndashPoor performance status limited life expectancy

Timing

bull RT at the moment of symptom onset

bull No place for bdquoprophylactic palliative RTldquo according to evidence based guidelines

ndashExceptions

bull Young patient good PS aim of local control

bull Imminent symptoms (superior vena cava syndrome central airway obstruction

Rodrigues Pract Rad Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 76

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 77

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 78

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 80

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 81

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 82

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 83

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 84

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 85

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 90

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 98

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 99

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Scoccianti Radiother Oncol 2012

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 100

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 101

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 102

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 103

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 104

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 105

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 106

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Page 58: SRO Tutorial Palliative Care 04.05.2012 Palliative Radiotherapy · 2018-02-22 · SRO Tutorial Palliative Care – Palliative Radiotherapy 30 Jacqueline Vock, Universitätsklinik

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 58

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull RT effective for improvement of

ndashThoracic symptoms (haemoptysis cough thoracic pain

dyspnoea airway obstruction) (Sirzeacuten Acta Oncol 2003 and others)

ndashQOL in about 13 of patients (Langendijk IJROBP 2000)

RT schedules

bull Systematic review (Fairchild JCO 264001-4011 2008)

ndash13 randomized trials 3473 patients

ndashdifferent RT schedules

ndashAim find optimal RT schedule for maximal palliation with

minimal toxicityneed for reirradiation

Thoracic symptoms

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 59

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz

Cancer

2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 60

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz Chow Hartsell Konski Cancer 2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 61

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemoptysis

bull Fig2 toux

733 689

812 802

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 62

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig3 doul thor 321 279

535 482

Cough

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 63

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 4 overall symptom burden

575 519

648 638

Thoracic pain

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 64

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 5 survie 1a

Cutoff (sensitivity analysis) BED[10] 35Gy vs LD

100 162

555 609

Overall symptom burden

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 65

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cutoff BED[10] 35Gy vs LD

265 217

Overall survival at 1y

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 66

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 7 Tox dysphagie

Cutoff BED[10] 30Gy vs LD

205 149

about x 2

Toxicity (dysphagia)

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 67

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomized trial 250 patients (Falk BMJ 2002)

bull Locally advanced non resectable NSCLC with minimal thoracic symptoms

bull Immediate vs delayed RT (at symptom onset)

bull In delayed arm 56 of patients died without RT

bull No difference in QOL odr OS

bull More acute toxicity in immediate RT arm

Randomized trial (Sundstrom Radiother Oncol 2005)

bull Advanced NSCLC

bull 2 RT schedules (5x4Gy vs 2x85 Gy) immediate RT

bull Stratification according to presenceabsence of thoracic symptoms

bull In asymptomatic patients no long term symptom control but important dysphagia

Timing

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 68

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull in 97 malignant

bull in 5-10 of lung cancer patients

bull Histology (exclude benign disease RT-chemosensible tumours

bull Generally spontanous improvement of symptoms by formation of collaterals

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 69

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Treatment

1 symptomatic

bull steroids

bull diuretics

bull Elevation of headthorax

2 causal bull chemotherapy (SCLC

lymphomas germinal tumours)

bull Endovascular stent placement

bull radiotherapy Palliative care in lung cancer ACCP

evidence- based clinical practice guidelines

(2nd edition)

Kvale Chest 2007

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 70

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

Radiotherapy

bull Mostly clinical response within 72 h

bull Complete clinical response at 2 w in 78 of patients with SCLC

and 63 of patients with NSCLC

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 71

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 72

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 73

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duhamel Atlas clinique des maladies

des voies aeacuteriennes Elsevier

wwwupmccancercenterscom

Endobronchial brachytherapy

Cochrane analysis (Cardona The Cochrane

Library 2008)

bull No improved

symptom relief by

addition of

endobronchial

brachytherapy to

EBRT

bull Indicated in selected

patients pretreated

by EBRT with

central

endobronchial

obstruction

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 74

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Ozkok Lung Cancer 2008

Endobronchial brachytherapy

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 75

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Take home lung cancer

Dosefractionation

bull Minimum 10x3 Gy 5xw or equivalent

ndash better symptom control and better overall survival

ndash But more toxicity

bull Short schedule for symptom control and limited toxicity

ndashPoor performance status limited life expectancy

Timing

bull RT at the moment of symptom onset

bull No place for bdquoprophylactic palliative RTldquo according to evidence based guidelines

ndashExceptions

bull Young patient good PS aim of local control

bull Imminent symptoms (superior vena cava syndrome central airway obstruction

Rodrigues Pract Rad Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 76

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 77

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 78

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 80

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 81

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 82

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 83

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 84

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 85

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 90

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 98

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 99

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Scoccianti Radiother Oncol 2012

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 100

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 101

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 102

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 103

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 104

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 105

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 106

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Page 59: SRO Tutorial Palliative Care 04.05.2012 Palliative Radiotherapy · 2018-02-22 · SRO Tutorial Palliative Care – Palliative Radiotherapy 30 Jacqueline Vock, Universitätsklinik

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 59

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz

Cancer

2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 60

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz Chow Hartsell Konski Cancer 2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 61

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemoptysis

bull Fig2 toux

733 689

812 802

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 62

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig3 doul thor 321 279

535 482

Cough

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 63

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 4 overall symptom burden

575 519

648 638

Thoracic pain

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 64

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 5 survie 1a

Cutoff (sensitivity analysis) BED[10] 35Gy vs LD

100 162

555 609

Overall symptom burden

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 65

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cutoff BED[10] 35Gy vs LD

265 217

Overall survival at 1y

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 66

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 7 Tox dysphagie

Cutoff BED[10] 30Gy vs LD

205 149

about x 2

Toxicity (dysphagia)

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 67

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomized trial 250 patients (Falk BMJ 2002)

bull Locally advanced non resectable NSCLC with minimal thoracic symptoms

bull Immediate vs delayed RT (at symptom onset)

bull In delayed arm 56 of patients died without RT

bull No difference in QOL odr OS

bull More acute toxicity in immediate RT arm

Randomized trial (Sundstrom Radiother Oncol 2005)

bull Advanced NSCLC

bull 2 RT schedules (5x4Gy vs 2x85 Gy) immediate RT

bull Stratification according to presenceabsence of thoracic symptoms

bull In asymptomatic patients no long term symptom control but important dysphagia

Timing

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 68

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull in 97 malignant

bull in 5-10 of lung cancer patients

bull Histology (exclude benign disease RT-chemosensible tumours

bull Generally spontanous improvement of symptoms by formation of collaterals

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 69

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Treatment

1 symptomatic

bull steroids

bull diuretics

bull Elevation of headthorax

2 causal bull chemotherapy (SCLC

lymphomas germinal tumours)

bull Endovascular stent placement

bull radiotherapy Palliative care in lung cancer ACCP

evidence- based clinical practice guidelines

(2nd edition)

Kvale Chest 2007

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 70

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

Radiotherapy

bull Mostly clinical response within 72 h

bull Complete clinical response at 2 w in 78 of patients with SCLC

and 63 of patients with NSCLC

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 71

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 72

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 73

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duhamel Atlas clinique des maladies

des voies aeacuteriennes Elsevier

wwwupmccancercenterscom

Endobronchial brachytherapy

Cochrane analysis (Cardona The Cochrane

Library 2008)

bull No improved

symptom relief by

addition of

endobronchial

brachytherapy to

EBRT

bull Indicated in selected

patients pretreated

by EBRT with

central

endobronchial

obstruction

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 74

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Ozkok Lung Cancer 2008

Endobronchial brachytherapy

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 75

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Take home lung cancer

Dosefractionation

bull Minimum 10x3 Gy 5xw or equivalent

ndash better symptom control and better overall survival

ndash But more toxicity

bull Short schedule for symptom control and limited toxicity

ndashPoor performance status limited life expectancy

Timing

bull RT at the moment of symptom onset

bull No place for bdquoprophylactic palliative RTldquo according to evidence based guidelines

ndashExceptions

bull Young patient good PS aim of local control

bull Imminent symptoms (superior vena cava syndrome central airway obstruction

Rodrigues Pract Rad Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 76

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 77

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 78

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 80

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 81

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 82

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 83

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 84

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 85

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 90

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 98

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 99

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Scoccianti Radiother Oncol 2012

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 100

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 101

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 102

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 103

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 104

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 105

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 106

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Page 60: SRO Tutorial Palliative Care 04.05.2012 Palliative Radiotherapy · 2018-02-22 · SRO Tutorial Palliative Care – Palliative Radiotherapy 30 Jacqueline Vock, Universitätsklinik

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 60

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lutz Chow Hartsell Konski Cancer 2007

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 61

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemoptysis

bull Fig2 toux

733 689

812 802

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 62

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig3 doul thor 321 279

535 482

Cough

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 63

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 4 overall symptom burden

575 519

648 638

Thoracic pain

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 64

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 5 survie 1a

Cutoff (sensitivity analysis) BED[10] 35Gy vs LD

100 162

555 609

Overall symptom burden

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 65

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cutoff BED[10] 35Gy vs LD

265 217

Overall survival at 1y

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 66

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 7 Tox dysphagie

Cutoff BED[10] 30Gy vs LD

205 149

about x 2

Toxicity (dysphagia)

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 67

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomized trial 250 patients (Falk BMJ 2002)

bull Locally advanced non resectable NSCLC with minimal thoracic symptoms

bull Immediate vs delayed RT (at symptom onset)

bull In delayed arm 56 of patients died without RT

bull No difference in QOL odr OS

bull More acute toxicity in immediate RT arm

Randomized trial (Sundstrom Radiother Oncol 2005)

bull Advanced NSCLC

bull 2 RT schedules (5x4Gy vs 2x85 Gy) immediate RT

bull Stratification according to presenceabsence of thoracic symptoms

bull In asymptomatic patients no long term symptom control but important dysphagia

Timing

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 68

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull in 97 malignant

bull in 5-10 of lung cancer patients

bull Histology (exclude benign disease RT-chemosensible tumours

bull Generally spontanous improvement of symptoms by formation of collaterals

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 69

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Treatment

1 symptomatic

bull steroids

bull diuretics

bull Elevation of headthorax

2 causal bull chemotherapy (SCLC

lymphomas germinal tumours)

bull Endovascular stent placement

bull radiotherapy Palliative care in lung cancer ACCP

evidence- based clinical practice guidelines

(2nd edition)

Kvale Chest 2007

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 70

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

Radiotherapy

bull Mostly clinical response within 72 h

bull Complete clinical response at 2 w in 78 of patients with SCLC

and 63 of patients with NSCLC

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 71

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 72

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 73

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duhamel Atlas clinique des maladies

des voies aeacuteriennes Elsevier

wwwupmccancercenterscom

Endobronchial brachytherapy

Cochrane analysis (Cardona The Cochrane

Library 2008)

bull No improved

symptom relief by

addition of

endobronchial

brachytherapy to

EBRT

bull Indicated in selected

patients pretreated

by EBRT with

central

endobronchial

obstruction

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 74

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Ozkok Lung Cancer 2008

Endobronchial brachytherapy

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 75

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Take home lung cancer

Dosefractionation

bull Minimum 10x3 Gy 5xw or equivalent

ndash better symptom control and better overall survival

ndash But more toxicity

bull Short schedule for symptom control and limited toxicity

ndashPoor performance status limited life expectancy

Timing

bull RT at the moment of symptom onset

bull No place for bdquoprophylactic palliative RTldquo according to evidence based guidelines

ndashExceptions

bull Young patient good PS aim of local control

bull Imminent symptoms (superior vena cava syndrome central airway obstruction

Rodrigues Pract Rad Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 76

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 77

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 78

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 80

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 81

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 82

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 83

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 84

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 85

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 90

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 98

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 99

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Scoccianti Radiother Oncol 2012

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 100

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 101

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 102

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 103

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 104

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 105

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 106

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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SRO Tutorial Palliative Care ndash Palliative Radiotherapy 61

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Haemoptysis

bull Fig2 toux

733 689

812 802

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 62

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig3 doul thor 321 279

535 482

Cough

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 63

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 4 overall symptom burden

575 519

648 638

Thoracic pain

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 64

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 5 survie 1a

Cutoff (sensitivity analysis) BED[10] 35Gy vs LD

100 162

555 609

Overall symptom burden

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 65

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cutoff BED[10] 35Gy vs LD

265 217

Overall survival at 1y

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 66

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 7 Tox dysphagie

Cutoff BED[10] 30Gy vs LD

205 149

about x 2

Toxicity (dysphagia)

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 67

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomized trial 250 patients (Falk BMJ 2002)

bull Locally advanced non resectable NSCLC with minimal thoracic symptoms

bull Immediate vs delayed RT (at symptom onset)

bull In delayed arm 56 of patients died without RT

bull No difference in QOL odr OS

bull More acute toxicity in immediate RT arm

Randomized trial (Sundstrom Radiother Oncol 2005)

bull Advanced NSCLC

bull 2 RT schedules (5x4Gy vs 2x85 Gy) immediate RT

bull Stratification according to presenceabsence of thoracic symptoms

bull In asymptomatic patients no long term symptom control but important dysphagia

Timing

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 68

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull in 97 malignant

bull in 5-10 of lung cancer patients

bull Histology (exclude benign disease RT-chemosensible tumours

bull Generally spontanous improvement of symptoms by formation of collaterals

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 69

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Treatment

1 symptomatic

bull steroids

bull diuretics

bull Elevation of headthorax

2 causal bull chemotherapy (SCLC

lymphomas germinal tumours)

bull Endovascular stent placement

bull radiotherapy Palliative care in lung cancer ACCP

evidence- based clinical practice guidelines

(2nd edition)

Kvale Chest 2007

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 70

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

Radiotherapy

bull Mostly clinical response within 72 h

bull Complete clinical response at 2 w in 78 of patients with SCLC

and 63 of patients with NSCLC

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 71

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 72

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 73

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duhamel Atlas clinique des maladies

des voies aeacuteriennes Elsevier

wwwupmccancercenterscom

Endobronchial brachytherapy

Cochrane analysis (Cardona The Cochrane

Library 2008)

bull No improved

symptom relief by

addition of

endobronchial

brachytherapy to

EBRT

bull Indicated in selected

patients pretreated

by EBRT with

central

endobronchial

obstruction

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 74

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Ozkok Lung Cancer 2008

Endobronchial brachytherapy

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 75

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Take home lung cancer

Dosefractionation

bull Minimum 10x3 Gy 5xw or equivalent

ndash better symptom control and better overall survival

ndash But more toxicity

bull Short schedule for symptom control and limited toxicity

ndashPoor performance status limited life expectancy

Timing

bull RT at the moment of symptom onset

bull No place for bdquoprophylactic palliative RTldquo according to evidence based guidelines

ndashExceptions

bull Young patient good PS aim of local control

bull Imminent symptoms (superior vena cava syndrome central airway obstruction

Rodrigues Pract Rad Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 76

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 77

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 78

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 80

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 81

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 82

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 83

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 84

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 85

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 90

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 98

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 99

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Scoccianti Radiother Oncol 2012

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 100

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 101

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 102

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 103

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 104

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 105

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 106

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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SRO Tutorial Palliative Care ndash Palliative Radiotherapy 62

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig3 doul thor 321 279

535 482

Cough

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 63

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 4 overall symptom burden

575 519

648 638

Thoracic pain

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 64

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 5 survie 1a

Cutoff (sensitivity analysis) BED[10] 35Gy vs LD

100 162

555 609

Overall symptom burden

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 65

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cutoff BED[10] 35Gy vs LD

265 217

Overall survival at 1y

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 66

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 7 Tox dysphagie

Cutoff BED[10] 30Gy vs LD

205 149

about x 2

Toxicity (dysphagia)

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 67

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomized trial 250 patients (Falk BMJ 2002)

bull Locally advanced non resectable NSCLC with minimal thoracic symptoms

bull Immediate vs delayed RT (at symptom onset)

bull In delayed arm 56 of patients died without RT

bull No difference in QOL odr OS

bull More acute toxicity in immediate RT arm

Randomized trial (Sundstrom Radiother Oncol 2005)

bull Advanced NSCLC

bull 2 RT schedules (5x4Gy vs 2x85 Gy) immediate RT

bull Stratification according to presenceabsence of thoracic symptoms

bull In asymptomatic patients no long term symptom control but important dysphagia

Timing

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 68

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull in 97 malignant

bull in 5-10 of lung cancer patients

bull Histology (exclude benign disease RT-chemosensible tumours

bull Generally spontanous improvement of symptoms by formation of collaterals

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 69

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Treatment

1 symptomatic

bull steroids

bull diuretics

bull Elevation of headthorax

2 causal bull chemotherapy (SCLC

lymphomas germinal tumours)

bull Endovascular stent placement

bull radiotherapy Palliative care in lung cancer ACCP

evidence- based clinical practice guidelines

(2nd edition)

Kvale Chest 2007

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 70

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

Radiotherapy

bull Mostly clinical response within 72 h

bull Complete clinical response at 2 w in 78 of patients with SCLC

and 63 of patients with NSCLC

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 71

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 72

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 73

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duhamel Atlas clinique des maladies

des voies aeacuteriennes Elsevier

wwwupmccancercenterscom

Endobronchial brachytherapy

Cochrane analysis (Cardona The Cochrane

Library 2008)

bull No improved

symptom relief by

addition of

endobronchial

brachytherapy to

EBRT

bull Indicated in selected

patients pretreated

by EBRT with

central

endobronchial

obstruction

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 74

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Ozkok Lung Cancer 2008

Endobronchial brachytherapy

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 75

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Take home lung cancer

Dosefractionation

bull Minimum 10x3 Gy 5xw or equivalent

ndash better symptom control and better overall survival

ndash But more toxicity

bull Short schedule for symptom control and limited toxicity

ndashPoor performance status limited life expectancy

Timing

bull RT at the moment of symptom onset

bull No place for bdquoprophylactic palliative RTldquo according to evidence based guidelines

ndashExceptions

bull Young patient good PS aim of local control

bull Imminent symptoms (superior vena cava syndrome central airway obstruction

Rodrigues Pract Rad Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 76

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 77

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 78

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 80

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 81

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 82

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 83

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 84

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 85

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 90

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 98

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 99

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Scoccianti Radiother Oncol 2012

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 100

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 101

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 102

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 103

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 104

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 105

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 106

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Page 63: SRO Tutorial Palliative Care 04.05.2012 Palliative Radiotherapy · 2018-02-22 · SRO Tutorial Palliative Care – Palliative Radiotherapy 30 Jacqueline Vock, Universitätsklinik

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 63

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 4 overall symptom burden

575 519

648 638

Thoracic pain

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 64

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 5 survie 1a

Cutoff (sensitivity analysis) BED[10] 35Gy vs LD

100 162

555 609

Overall symptom burden

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 65

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cutoff BED[10] 35Gy vs LD

265 217

Overall survival at 1y

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 66

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 7 Tox dysphagie

Cutoff BED[10] 30Gy vs LD

205 149

about x 2

Toxicity (dysphagia)

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 67

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomized trial 250 patients (Falk BMJ 2002)

bull Locally advanced non resectable NSCLC with minimal thoracic symptoms

bull Immediate vs delayed RT (at symptom onset)

bull In delayed arm 56 of patients died without RT

bull No difference in QOL odr OS

bull More acute toxicity in immediate RT arm

Randomized trial (Sundstrom Radiother Oncol 2005)

bull Advanced NSCLC

bull 2 RT schedules (5x4Gy vs 2x85 Gy) immediate RT

bull Stratification according to presenceabsence of thoracic symptoms

bull In asymptomatic patients no long term symptom control but important dysphagia

Timing

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 68

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull in 97 malignant

bull in 5-10 of lung cancer patients

bull Histology (exclude benign disease RT-chemosensible tumours

bull Generally spontanous improvement of symptoms by formation of collaterals

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 69

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Treatment

1 symptomatic

bull steroids

bull diuretics

bull Elevation of headthorax

2 causal bull chemotherapy (SCLC

lymphomas germinal tumours)

bull Endovascular stent placement

bull radiotherapy Palliative care in lung cancer ACCP

evidence- based clinical practice guidelines

(2nd edition)

Kvale Chest 2007

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 70

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

Radiotherapy

bull Mostly clinical response within 72 h

bull Complete clinical response at 2 w in 78 of patients with SCLC

and 63 of patients with NSCLC

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 71

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 72

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 73

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duhamel Atlas clinique des maladies

des voies aeacuteriennes Elsevier

wwwupmccancercenterscom

Endobronchial brachytherapy

Cochrane analysis (Cardona The Cochrane

Library 2008)

bull No improved

symptom relief by

addition of

endobronchial

brachytherapy to

EBRT

bull Indicated in selected

patients pretreated

by EBRT with

central

endobronchial

obstruction

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 74

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Ozkok Lung Cancer 2008

Endobronchial brachytherapy

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 75

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Take home lung cancer

Dosefractionation

bull Minimum 10x3 Gy 5xw or equivalent

ndash better symptom control and better overall survival

ndash But more toxicity

bull Short schedule for symptom control and limited toxicity

ndashPoor performance status limited life expectancy

Timing

bull RT at the moment of symptom onset

bull No place for bdquoprophylactic palliative RTldquo according to evidence based guidelines

ndashExceptions

bull Young patient good PS aim of local control

bull Imminent symptoms (superior vena cava syndrome central airway obstruction

Rodrigues Pract Rad Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 76

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 77

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 78

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 80

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 81

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 82

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 83

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 84

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 85

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 90

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 98

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 99

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Scoccianti Radiother Oncol 2012

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 100

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 101

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 102

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 103

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 104

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 105

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 106

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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SRO Tutorial Palliative Care ndash Palliative Radiotherapy 64

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 5 survie 1a

Cutoff (sensitivity analysis) BED[10] 35Gy vs LD

100 162

555 609

Overall symptom burden

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 65

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cutoff BED[10] 35Gy vs LD

265 217

Overall survival at 1y

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 66

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 7 Tox dysphagie

Cutoff BED[10] 30Gy vs LD

205 149

about x 2

Toxicity (dysphagia)

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 67

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomized trial 250 patients (Falk BMJ 2002)

bull Locally advanced non resectable NSCLC with minimal thoracic symptoms

bull Immediate vs delayed RT (at symptom onset)

bull In delayed arm 56 of patients died without RT

bull No difference in QOL odr OS

bull More acute toxicity in immediate RT arm

Randomized trial (Sundstrom Radiother Oncol 2005)

bull Advanced NSCLC

bull 2 RT schedules (5x4Gy vs 2x85 Gy) immediate RT

bull Stratification according to presenceabsence of thoracic symptoms

bull In asymptomatic patients no long term symptom control but important dysphagia

Timing

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 68

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull in 97 malignant

bull in 5-10 of lung cancer patients

bull Histology (exclude benign disease RT-chemosensible tumours

bull Generally spontanous improvement of symptoms by formation of collaterals

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 69

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Treatment

1 symptomatic

bull steroids

bull diuretics

bull Elevation of headthorax

2 causal bull chemotherapy (SCLC

lymphomas germinal tumours)

bull Endovascular stent placement

bull radiotherapy Palliative care in lung cancer ACCP

evidence- based clinical practice guidelines

(2nd edition)

Kvale Chest 2007

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 70

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

Radiotherapy

bull Mostly clinical response within 72 h

bull Complete clinical response at 2 w in 78 of patients with SCLC

and 63 of patients with NSCLC

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 71

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 72

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 73

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duhamel Atlas clinique des maladies

des voies aeacuteriennes Elsevier

wwwupmccancercenterscom

Endobronchial brachytherapy

Cochrane analysis (Cardona The Cochrane

Library 2008)

bull No improved

symptom relief by

addition of

endobronchial

brachytherapy to

EBRT

bull Indicated in selected

patients pretreated

by EBRT with

central

endobronchial

obstruction

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 74

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Ozkok Lung Cancer 2008

Endobronchial brachytherapy

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 75

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Take home lung cancer

Dosefractionation

bull Minimum 10x3 Gy 5xw or equivalent

ndash better symptom control and better overall survival

ndash But more toxicity

bull Short schedule for symptom control and limited toxicity

ndashPoor performance status limited life expectancy

Timing

bull RT at the moment of symptom onset

bull No place for bdquoprophylactic palliative RTldquo according to evidence based guidelines

ndashExceptions

bull Young patient good PS aim of local control

bull Imminent symptoms (superior vena cava syndrome central airway obstruction

Rodrigues Pract Rad Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 76

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 77

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 78

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 80

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 81

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 82

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 83

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 84

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 85

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 90

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 98

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 99

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Scoccianti Radiother Oncol 2012

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 100

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 101

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 102

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 103

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 104

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 105

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 106

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Page 65: SRO Tutorial Palliative Care 04.05.2012 Palliative Radiotherapy · 2018-02-22 · SRO Tutorial Palliative Care – Palliative Radiotherapy 30 Jacqueline Vock, Universitätsklinik

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 65

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Cutoff BED[10] 35Gy vs LD

265 217

Overall survival at 1y

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 66

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 7 Tox dysphagie

Cutoff BED[10] 30Gy vs LD

205 149

about x 2

Toxicity (dysphagia)

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 67

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomized trial 250 patients (Falk BMJ 2002)

bull Locally advanced non resectable NSCLC with minimal thoracic symptoms

bull Immediate vs delayed RT (at symptom onset)

bull In delayed arm 56 of patients died without RT

bull No difference in QOL odr OS

bull More acute toxicity in immediate RT arm

Randomized trial (Sundstrom Radiother Oncol 2005)

bull Advanced NSCLC

bull 2 RT schedules (5x4Gy vs 2x85 Gy) immediate RT

bull Stratification according to presenceabsence of thoracic symptoms

bull In asymptomatic patients no long term symptom control but important dysphagia

Timing

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 68

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull in 97 malignant

bull in 5-10 of lung cancer patients

bull Histology (exclude benign disease RT-chemosensible tumours

bull Generally spontanous improvement of symptoms by formation of collaterals

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 69

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Treatment

1 symptomatic

bull steroids

bull diuretics

bull Elevation of headthorax

2 causal bull chemotherapy (SCLC

lymphomas germinal tumours)

bull Endovascular stent placement

bull radiotherapy Palliative care in lung cancer ACCP

evidence- based clinical practice guidelines

(2nd edition)

Kvale Chest 2007

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 70

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

Radiotherapy

bull Mostly clinical response within 72 h

bull Complete clinical response at 2 w in 78 of patients with SCLC

and 63 of patients with NSCLC

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 71

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 72

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 73

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duhamel Atlas clinique des maladies

des voies aeacuteriennes Elsevier

wwwupmccancercenterscom

Endobronchial brachytherapy

Cochrane analysis (Cardona The Cochrane

Library 2008)

bull No improved

symptom relief by

addition of

endobronchial

brachytherapy to

EBRT

bull Indicated in selected

patients pretreated

by EBRT with

central

endobronchial

obstruction

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 74

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Ozkok Lung Cancer 2008

Endobronchial brachytherapy

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 75

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Take home lung cancer

Dosefractionation

bull Minimum 10x3 Gy 5xw or equivalent

ndash better symptom control and better overall survival

ndash But more toxicity

bull Short schedule for symptom control and limited toxicity

ndashPoor performance status limited life expectancy

Timing

bull RT at the moment of symptom onset

bull No place for bdquoprophylactic palliative RTldquo according to evidence based guidelines

ndashExceptions

bull Young patient good PS aim of local control

bull Imminent symptoms (superior vena cava syndrome central airway obstruction

Rodrigues Pract Rad Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 76

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 77

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 78

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 80

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 81

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 82

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 83

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 84

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 85

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 90

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 98

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 99

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Scoccianti Radiother Oncol 2012

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 100

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 101

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 102

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 103

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 104

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 105

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 106

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Page 66: SRO Tutorial Palliative Care 04.05.2012 Palliative Radiotherapy · 2018-02-22 · SRO Tutorial Palliative Care – Palliative Radiotherapy 30 Jacqueline Vock, Universitätsklinik

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 66

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Fig 7 Tox dysphagie

Cutoff BED[10] 30Gy vs LD

205 149

about x 2

Toxicity (dysphagia)

Fairchild JCO 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 67

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomized trial 250 patients (Falk BMJ 2002)

bull Locally advanced non resectable NSCLC with minimal thoracic symptoms

bull Immediate vs delayed RT (at symptom onset)

bull In delayed arm 56 of patients died without RT

bull No difference in QOL odr OS

bull More acute toxicity in immediate RT arm

Randomized trial (Sundstrom Radiother Oncol 2005)

bull Advanced NSCLC

bull 2 RT schedules (5x4Gy vs 2x85 Gy) immediate RT

bull Stratification according to presenceabsence of thoracic symptoms

bull In asymptomatic patients no long term symptom control but important dysphagia

Timing

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 68

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull in 97 malignant

bull in 5-10 of lung cancer patients

bull Histology (exclude benign disease RT-chemosensible tumours

bull Generally spontanous improvement of symptoms by formation of collaterals

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 69

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Treatment

1 symptomatic

bull steroids

bull diuretics

bull Elevation of headthorax

2 causal bull chemotherapy (SCLC

lymphomas germinal tumours)

bull Endovascular stent placement

bull radiotherapy Palliative care in lung cancer ACCP

evidence- based clinical practice guidelines

(2nd edition)

Kvale Chest 2007

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 70

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

Radiotherapy

bull Mostly clinical response within 72 h

bull Complete clinical response at 2 w in 78 of patients with SCLC

and 63 of patients with NSCLC

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 71

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 72

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 73

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duhamel Atlas clinique des maladies

des voies aeacuteriennes Elsevier

wwwupmccancercenterscom

Endobronchial brachytherapy

Cochrane analysis (Cardona The Cochrane

Library 2008)

bull No improved

symptom relief by

addition of

endobronchial

brachytherapy to

EBRT

bull Indicated in selected

patients pretreated

by EBRT with

central

endobronchial

obstruction

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 74

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Ozkok Lung Cancer 2008

Endobronchial brachytherapy

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 75

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Take home lung cancer

Dosefractionation

bull Minimum 10x3 Gy 5xw or equivalent

ndash better symptom control and better overall survival

ndash But more toxicity

bull Short schedule for symptom control and limited toxicity

ndashPoor performance status limited life expectancy

Timing

bull RT at the moment of symptom onset

bull No place for bdquoprophylactic palliative RTldquo according to evidence based guidelines

ndashExceptions

bull Young patient good PS aim of local control

bull Imminent symptoms (superior vena cava syndrome central airway obstruction

Rodrigues Pract Rad Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 76

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 77

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 78

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 80

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 81

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 82

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 83

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 84

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 85

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 90

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 98

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 99

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Scoccianti Radiother Oncol 2012

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 100

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 101

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 102

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 103

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 104

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 105

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 106

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Page 67: SRO Tutorial Palliative Care 04.05.2012 Palliative Radiotherapy · 2018-02-22 · SRO Tutorial Palliative Care – Palliative Radiotherapy 30 Jacqueline Vock, Universitätsklinik

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 67

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomized trial 250 patients (Falk BMJ 2002)

bull Locally advanced non resectable NSCLC with minimal thoracic symptoms

bull Immediate vs delayed RT (at symptom onset)

bull In delayed arm 56 of patients died without RT

bull No difference in QOL odr OS

bull More acute toxicity in immediate RT arm

Randomized trial (Sundstrom Radiother Oncol 2005)

bull Advanced NSCLC

bull 2 RT schedules (5x4Gy vs 2x85 Gy) immediate RT

bull Stratification according to presenceabsence of thoracic symptoms

bull In asymptomatic patients no long term symptom control but important dysphagia

Timing

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 68

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull in 97 malignant

bull in 5-10 of lung cancer patients

bull Histology (exclude benign disease RT-chemosensible tumours

bull Generally spontanous improvement of symptoms by formation of collaterals

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 69

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Treatment

1 symptomatic

bull steroids

bull diuretics

bull Elevation of headthorax

2 causal bull chemotherapy (SCLC

lymphomas germinal tumours)

bull Endovascular stent placement

bull radiotherapy Palliative care in lung cancer ACCP

evidence- based clinical practice guidelines

(2nd edition)

Kvale Chest 2007

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 70

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

Radiotherapy

bull Mostly clinical response within 72 h

bull Complete clinical response at 2 w in 78 of patients with SCLC

and 63 of patients with NSCLC

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 71

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 72

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 73

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duhamel Atlas clinique des maladies

des voies aeacuteriennes Elsevier

wwwupmccancercenterscom

Endobronchial brachytherapy

Cochrane analysis (Cardona The Cochrane

Library 2008)

bull No improved

symptom relief by

addition of

endobronchial

brachytherapy to

EBRT

bull Indicated in selected

patients pretreated

by EBRT with

central

endobronchial

obstruction

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 74

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Ozkok Lung Cancer 2008

Endobronchial brachytherapy

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 75

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Take home lung cancer

Dosefractionation

bull Minimum 10x3 Gy 5xw or equivalent

ndash better symptom control and better overall survival

ndash But more toxicity

bull Short schedule for symptom control and limited toxicity

ndashPoor performance status limited life expectancy

Timing

bull RT at the moment of symptom onset

bull No place for bdquoprophylactic palliative RTldquo according to evidence based guidelines

ndashExceptions

bull Young patient good PS aim of local control

bull Imminent symptoms (superior vena cava syndrome central airway obstruction

Rodrigues Pract Rad Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 76

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 77

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 78

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 80

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 81

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 82

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 83

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 84

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 85

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 90

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 98

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 99

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Scoccianti Radiother Oncol 2012

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 100

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 101

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 102

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 103

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 104

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 105

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 106

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Page 68: SRO Tutorial Palliative Care 04.05.2012 Palliative Radiotherapy · 2018-02-22 · SRO Tutorial Palliative Care – Palliative Radiotherapy 30 Jacqueline Vock, Universitätsklinik

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 68

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull in 97 malignant

bull in 5-10 of lung cancer patients

bull Histology (exclude benign disease RT-chemosensible tumours

bull Generally spontanous improvement of symptoms by formation of collaterals

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 69

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Treatment

1 symptomatic

bull steroids

bull diuretics

bull Elevation of headthorax

2 causal bull chemotherapy (SCLC

lymphomas germinal tumours)

bull Endovascular stent placement

bull radiotherapy Palliative care in lung cancer ACCP

evidence- based clinical practice guidelines

(2nd edition)

Kvale Chest 2007

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 70

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

Radiotherapy

bull Mostly clinical response within 72 h

bull Complete clinical response at 2 w in 78 of patients with SCLC

and 63 of patients with NSCLC

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 71

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 72

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 73

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duhamel Atlas clinique des maladies

des voies aeacuteriennes Elsevier

wwwupmccancercenterscom

Endobronchial brachytherapy

Cochrane analysis (Cardona The Cochrane

Library 2008)

bull No improved

symptom relief by

addition of

endobronchial

brachytherapy to

EBRT

bull Indicated in selected

patients pretreated

by EBRT with

central

endobronchial

obstruction

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 74

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Ozkok Lung Cancer 2008

Endobronchial brachytherapy

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 75

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Take home lung cancer

Dosefractionation

bull Minimum 10x3 Gy 5xw or equivalent

ndash better symptom control and better overall survival

ndash But more toxicity

bull Short schedule for symptom control and limited toxicity

ndashPoor performance status limited life expectancy

Timing

bull RT at the moment of symptom onset

bull No place for bdquoprophylactic palliative RTldquo according to evidence based guidelines

ndashExceptions

bull Young patient good PS aim of local control

bull Imminent symptoms (superior vena cava syndrome central airway obstruction

Rodrigues Pract Rad Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 76

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 77

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 78

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 80

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 81

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 82

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 83

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 84

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 85

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 90

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 98

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 99

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Scoccianti Radiother Oncol 2012

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 100

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 101

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 102

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 103

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 104

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 105

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 106

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Page 69: SRO Tutorial Palliative Care 04.05.2012 Palliative Radiotherapy · 2018-02-22 · SRO Tutorial Palliative Care – Palliative Radiotherapy 30 Jacqueline Vock, Universitätsklinik

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 69

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Treatment

1 symptomatic

bull steroids

bull diuretics

bull Elevation of headthorax

2 causal bull chemotherapy (SCLC

lymphomas germinal tumours)

bull Endovascular stent placement

bull radiotherapy Palliative care in lung cancer ACCP

evidence- based clinical practice guidelines

(2nd edition)

Kvale Chest 2007

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 70

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

Radiotherapy

bull Mostly clinical response within 72 h

bull Complete clinical response at 2 w in 78 of patients with SCLC

and 63 of patients with NSCLC

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 71

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 72

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 73

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duhamel Atlas clinique des maladies

des voies aeacuteriennes Elsevier

wwwupmccancercenterscom

Endobronchial brachytherapy

Cochrane analysis (Cardona The Cochrane

Library 2008)

bull No improved

symptom relief by

addition of

endobronchial

brachytherapy to

EBRT

bull Indicated in selected

patients pretreated

by EBRT with

central

endobronchial

obstruction

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 74

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Ozkok Lung Cancer 2008

Endobronchial brachytherapy

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 75

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Take home lung cancer

Dosefractionation

bull Minimum 10x3 Gy 5xw or equivalent

ndash better symptom control and better overall survival

ndash But more toxicity

bull Short schedule for symptom control and limited toxicity

ndashPoor performance status limited life expectancy

Timing

bull RT at the moment of symptom onset

bull No place for bdquoprophylactic palliative RTldquo according to evidence based guidelines

ndashExceptions

bull Young patient good PS aim of local control

bull Imminent symptoms (superior vena cava syndrome central airway obstruction

Rodrigues Pract Rad Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 76

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 77

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 78

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 80

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 81

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 82

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 83

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 84

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 85

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 90

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 98

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 99

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Scoccianti Radiother Oncol 2012

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 100

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 101

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 102

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 103

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 104

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 105

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 106

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Page 70: SRO Tutorial Palliative Care 04.05.2012 Palliative Radiotherapy · 2018-02-22 · SRO Tutorial Palliative Care – Palliative Radiotherapy 30 Jacqueline Vock, Universitätsklinik

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 70

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

Radiotherapy

bull Mostly clinical response within 72 h

bull Complete clinical response at 2 w in 78 of patients with SCLC

and 63 of patients with NSCLC

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 71

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 72

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 73

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duhamel Atlas clinique des maladies

des voies aeacuteriennes Elsevier

wwwupmccancercenterscom

Endobronchial brachytherapy

Cochrane analysis (Cardona The Cochrane

Library 2008)

bull No improved

symptom relief by

addition of

endobronchial

brachytherapy to

EBRT

bull Indicated in selected

patients pretreated

by EBRT with

central

endobronchial

obstruction

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 74

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Ozkok Lung Cancer 2008

Endobronchial brachytherapy

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 75

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Take home lung cancer

Dosefractionation

bull Minimum 10x3 Gy 5xw or equivalent

ndash better symptom control and better overall survival

ndash But more toxicity

bull Short schedule for symptom control and limited toxicity

ndashPoor performance status limited life expectancy

Timing

bull RT at the moment of symptom onset

bull No place for bdquoprophylactic palliative RTldquo according to evidence based guidelines

ndashExceptions

bull Young patient good PS aim of local control

bull Imminent symptoms (superior vena cava syndrome central airway obstruction

Rodrigues Pract Rad Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 76

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 77

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 78

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 80

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 81

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 82

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 83

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 84

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 85

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 90

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 98

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 99

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Scoccianti Radiother Oncol 2012

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 100

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 101

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 102

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 103

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 104

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 105

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 106

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Page 71: SRO Tutorial Palliative Care 04.05.2012 Palliative Radiotherapy · 2018-02-22 · SRO Tutorial Palliative Care – Palliative Radiotherapy 30 Jacqueline Vock, Universitätsklinik

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 71

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 72

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 73

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duhamel Atlas clinique des maladies

des voies aeacuteriennes Elsevier

wwwupmccancercenterscom

Endobronchial brachytherapy

Cochrane analysis (Cardona The Cochrane

Library 2008)

bull No improved

symptom relief by

addition of

endobronchial

brachytherapy to

EBRT

bull Indicated in selected

patients pretreated

by EBRT with

central

endobronchial

obstruction

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 74

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Ozkok Lung Cancer 2008

Endobronchial brachytherapy

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 75

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Take home lung cancer

Dosefractionation

bull Minimum 10x3 Gy 5xw or equivalent

ndash better symptom control and better overall survival

ndash But more toxicity

bull Short schedule for symptom control and limited toxicity

ndashPoor performance status limited life expectancy

Timing

bull RT at the moment of symptom onset

bull No place for bdquoprophylactic palliative RTldquo according to evidence based guidelines

ndashExceptions

bull Young patient good PS aim of local control

bull Imminent symptoms (superior vena cava syndrome central airway obstruction

Rodrigues Pract Rad Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 76

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 77

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 78

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 80

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 81

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 82

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 83

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 84

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 85

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 90

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 98

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 99

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Scoccianti Radiother Oncol 2012

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 100

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 101

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 102

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 103

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 104

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 105

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 106

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Page 72: SRO Tutorial Palliative Care 04.05.2012 Palliative Radiotherapy · 2018-02-22 · SRO Tutorial Palliative Care – Palliative Radiotherapy 30 Jacqueline Vock, Universitätsklinik

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 72

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Rowell Clin Oncol (R Coll Radiol) 2002

Superior vena cava syndrome

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 73

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duhamel Atlas clinique des maladies

des voies aeacuteriennes Elsevier

wwwupmccancercenterscom

Endobronchial brachytherapy

Cochrane analysis (Cardona The Cochrane

Library 2008)

bull No improved

symptom relief by

addition of

endobronchial

brachytherapy to

EBRT

bull Indicated in selected

patients pretreated

by EBRT with

central

endobronchial

obstruction

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 74

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Ozkok Lung Cancer 2008

Endobronchial brachytherapy

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 75

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Take home lung cancer

Dosefractionation

bull Minimum 10x3 Gy 5xw or equivalent

ndash better symptom control and better overall survival

ndash But more toxicity

bull Short schedule for symptom control and limited toxicity

ndashPoor performance status limited life expectancy

Timing

bull RT at the moment of symptom onset

bull No place for bdquoprophylactic palliative RTldquo according to evidence based guidelines

ndashExceptions

bull Young patient good PS aim of local control

bull Imminent symptoms (superior vena cava syndrome central airway obstruction

Rodrigues Pract Rad Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 76

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 77

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 78

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 80

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 81

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 82

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 83

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 84

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 85

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 90

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 98

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 99

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Scoccianti Radiother Oncol 2012

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 100

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 101

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 102

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 103

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 104

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 105

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 106

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Page 73: SRO Tutorial Palliative Care 04.05.2012 Palliative Radiotherapy · 2018-02-22 · SRO Tutorial Palliative Care – Palliative Radiotherapy 30 Jacqueline Vock, Universitätsklinik

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 73

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Duhamel Atlas clinique des maladies

des voies aeacuteriennes Elsevier

wwwupmccancercenterscom

Endobronchial brachytherapy

Cochrane analysis (Cardona The Cochrane

Library 2008)

bull No improved

symptom relief by

addition of

endobronchial

brachytherapy to

EBRT

bull Indicated in selected

patients pretreated

by EBRT with

central

endobronchial

obstruction

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 74

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Ozkok Lung Cancer 2008

Endobronchial brachytherapy

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 75

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Take home lung cancer

Dosefractionation

bull Minimum 10x3 Gy 5xw or equivalent

ndash better symptom control and better overall survival

ndash But more toxicity

bull Short schedule for symptom control and limited toxicity

ndashPoor performance status limited life expectancy

Timing

bull RT at the moment of symptom onset

bull No place for bdquoprophylactic palliative RTldquo according to evidence based guidelines

ndashExceptions

bull Young patient good PS aim of local control

bull Imminent symptoms (superior vena cava syndrome central airway obstruction

Rodrigues Pract Rad Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 76

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 77

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 78

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 80

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 81

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 82

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 83

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 84

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 85

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 90

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 98

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 99

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Scoccianti Radiother Oncol 2012

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 100

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 101

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 102

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 103

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 104

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 105

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 106

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Page 74: SRO Tutorial Palliative Care 04.05.2012 Palliative Radiotherapy · 2018-02-22 · SRO Tutorial Palliative Care – Palliative Radiotherapy 30 Jacqueline Vock, Universitätsklinik

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 74

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Ozkok Lung Cancer 2008

Endobronchial brachytherapy

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 75

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Take home lung cancer

Dosefractionation

bull Minimum 10x3 Gy 5xw or equivalent

ndash better symptom control and better overall survival

ndash But more toxicity

bull Short schedule for symptom control and limited toxicity

ndashPoor performance status limited life expectancy

Timing

bull RT at the moment of symptom onset

bull No place for bdquoprophylactic palliative RTldquo according to evidence based guidelines

ndashExceptions

bull Young patient good PS aim of local control

bull Imminent symptoms (superior vena cava syndrome central airway obstruction

Rodrigues Pract Rad Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 76

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 77

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 78

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 80

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 81

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 82

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 83

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 84

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 85

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 90

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 98

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 99

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Scoccianti Radiother Oncol 2012

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 100

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 101

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 102

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 103

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 104

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 105

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 106

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Page 75: SRO Tutorial Palliative Care 04.05.2012 Palliative Radiotherapy · 2018-02-22 · SRO Tutorial Palliative Care – Palliative Radiotherapy 30 Jacqueline Vock, Universitätsklinik

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 75

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Take home lung cancer

Dosefractionation

bull Minimum 10x3 Gy 5xw or equivalent

ndash better symptom control and better overall survival

ndash But more toxicity

bull Short schedule for symptom control and limited toxicity

ndashPoor performance status limited life expectancy

Timing

bull RT at the moment of symptom onset

bull No place for bdquoprophylactic palliative RTldquo according to evidence based guidelines

ndashExceptions

bull Young patient good PS aim of local control

bull Imminent symptoms (superior vena cava syndrome central airway obstruction

Rodrigues Pract Rad Oncol 2011

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 76

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 77

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 78

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 80

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 81

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 82

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 83

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 84

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 85

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 90

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 98

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 99

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Scoccianti Radiother Oncol 2012

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 100

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 101

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 102

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 103

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 104

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 105

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 106

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Page 76: SRO Tutorial Palliative Care 04.05.2012 Palliative Radiotherapy · 2018-02-22 · SRO Tutorial Palliative Care – Palliative Radiotherapy 30 Jacqueline Vock, Universitätsklinik

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 76

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 77

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 78

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 80

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 81

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 82

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 83

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 84

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 85

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 90

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 98

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 99

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Scoccianti Radiother Oncol 2012

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 100

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 101

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 102

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 103

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 104

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 105

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 106

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Page 77: SRO Tutorial Palliative Care 04.05.2012 Palliative Radiotherapy · 2018-02-22 · SRO Tutorial Palliative Care – Palliative Radiotherapy 30 Jacqueline Vock, Universitätsklinik

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 77

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 78

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 80

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 81

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 82

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 83

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 84

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 85

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 90

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 98

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 99

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Scoccianti Radiother Oncol 2012

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 100

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 101

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 102

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 103

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 104

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 105

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 106

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Page 78: SRO Tutorial Palliative Care 04.05.2012 Palliative Radiotherapy · 2018-02-22 · SRO Tutorial Palliative Care – Palliative Radiotherapy 30 Jacqueline Vock, Universitätsklinik

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 78

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Superior vena cava syndrome

bull RT effective

bull Consider stent

Endobronchial brachytherapy

bull Indicated in selected patients pretreated by EBRT with

central endobronchial obstruction

Take home lung cancer

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 80

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 81

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 82

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 83

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 84

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 85

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 90

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 98

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 99

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Scoccianti Radiother Oncol 2012

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 100

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 101

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 102

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 103

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 104

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 105

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 106

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Page 79: SRO Tutorial Palliative Care 04.05.2012 Palliative Radiotherapy · 2018-02-22 · SRO Tutorial Palliative Care – Palliative Radiotherapy 30 Jacqueline Vock, Universitätsklinik

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 79

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Diseases of the Esophagus 2005

65 patients Stent vs 3 x 7 Gy brachytherapy in 2-4 we Dysphagia ge grade 2 T4 or M1 Estimated OS gt 1 month Stent bdquoself-expandableldquo Ultraflex metal with cover Stent 10 -15 cm Brachytherapy 10 mm applicator if possible (17mm) Brachytherapy 10 mm margin craniocaudally Brachytherapy prescription depth 10 mm HRQL QLQ Nr C30

Dysphagia

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 80

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 81

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 82

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 83

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 84

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 85

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 90

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 98

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 99

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Scoccianti Radiother Oncol 2012

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 100

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 101

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 102

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 103

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 104

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 105

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 106

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Page 80: SRO Tutorial Palliative Care 04.05.2012 Palliative Radiotherapy · 2018-02-22 · SRO Tutorial Palliative Care – Palliative Radiotherapy 30 Jacqueline Vock, Universitätsklinik

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 80

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results

bull OS comparable (around 120 days)

bull 2 fistulas in stent1 in brachytherapy group

bull 1 bleeding in stent group

bull 2 perforations in brachytherapy group

bull QOL after 1 month stent = brachytherapy

bull QOL after 3 months stent = brachytherapy

bull QOL after 6 months stent worse than brachytherapy

bull More instant relief of dysphagia by stent but QOL more stable in brachytherapy

group

bull Patients with better prognosis should be treated by brachytherapy

Bergquist Diseases of the Esophagus 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 81

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 82

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 83

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 84

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 85

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 90

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 98

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 99

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Scoccianti Radiother Oncol 2012

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 100

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 101

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 102

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 103

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 104

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 105

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 106

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Page 81: SRO Tutorial Palliative Care 04.05.2012 Palliative Radiotherapy · 2018-02-22 · SRO Tutorial Palliative Care – Palliative Radiotherapy 30 Jacqueline Vock, Universitätsklinik

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 81

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 82

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 83

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 84

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 85

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 90

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 98

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 99

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Scoccianti Radiother Oncol 2012

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 100

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 101

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 102

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 103

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 104

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 105

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 106

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Page 82: SRO Tutorial Palliative Care 04.05.2012 Palliative Radiotherapy · 2018-02-22 · SRO Tutorial Palliative Care – Palliative Radiotherapy 30 Jacqueline Vock, Universitätsklinik

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 82

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash209 patients

ndashStent vs brachytherapy (SD)

ndashStent bdquoself-expandableldquo Ultraflex metal with cover

ndashBrachytherapy 1 x 12 Gy

ndashBrachytherapy prescription depth

ndashEndpoint QOL

ndashEORTC QLQ C30

Homs Eur J CancerLancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 83

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 84

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 85

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 90

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 98

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 99

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Scoccianti Radiother Oncol 2012

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 100

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 101

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 102

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 103

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 104

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 105

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 106

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Page 83: SRO Tutorial Palliative Care 04.05.2012 Palliative Radiotherapy · 2018-02-22 · SRO Tutorial Palliative Care – Palliative Radiotherapy 30 Jacqueline Vock, Universitätsklinik

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 83

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

ndash Results bull More complications in stent arm

ndash Fistula 6 vs 3

ndash Perforation 2 vs 2

ndash bleeding 14 vs 5

ndash pain3 vs 1

bull More rapid improvement of dysphagia in stent arm

bull Dysphagia score at 1 month Stent = Brachytherapy

bull Long-term relief of dysphagia better after brachytherapy

bull QOL in brachytherapy arm better

bull Costs comparable

bull Better for QOL long-term relief of dysphagia less complications brachytherapy

bull bad prognosis Stent

bull Single Dose feasible

Homs Eur J Cancer 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 84

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 85

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 90

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 98

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 99

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Scoccianti Radiother Oncol 2012

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 100

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 101

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 102

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 103

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 104

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 105

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 106

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Page 84: SRO Tutorial Palliative Care 04.05.2012 Palliative Radiotherapy · 2018-02-22 · SRO Tutorial Palliative Care – Palliative Radiotherapy 30 Jacqueline Vock, Universitätsklinik

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 84

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 85

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 90

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 98

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 99

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Scoccianti Radiother Oncol 2012

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 100

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 101

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 102

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 103

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 104

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 105

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 106

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Page 85: SRO Tutorial Palliative Care 04.05.2012 Palliative Radiotherapy · 2018-02-22 · SRO Tutorial Palliative Care – Palliative Radiotherapy 30 Jacqueline Vock, Universitätsklinik

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 85

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Randomisierte Studien

Homs Lancet 2004

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 90

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 98

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 99

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Scoccianti Radiother Oncol 2012

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 100

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 101

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 102

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 103

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 104

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 105

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 106

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Page 86: SRO Tutorial Palliative Care 04.05.2012 Palliative Radiotherapy · 2018-02-22 · SRO Tutorial Palliative Care – Palliative Radiotherapy 30 Jacqueline Vock, Universitätsklinik

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 86

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull 3x6 Gy and 2x8 Gy equally effective and toxic

IJROBP 2002

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 90

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 98

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 99

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Scoccianti Radiother Oncol 2012

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 100

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 101

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 102

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 103

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 104

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 105

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 106

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Page 87: SRO Tutorial Palliative Care 04.05.2012 Palliative Radiotherapy · 2018-02-22 · SRO Tutorial Palliative Care – Palliative Radiotherapy 30 Jacqueline Vock, Universitätsklinik

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 87

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neg prognostic factors in 607 pat

ndash Tumor length gt 10 cm

ndash Performance status

ndash Distant metastases

ndash Grade of dysphagia and tumour histology are no independant prognostic

factors

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 90

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 98

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 99

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Scoccianti Radiother Oncol 2012

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 100

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 101

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 102

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 103

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 104

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 105

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 106

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Page 88: SRO Tutorial Palliative Care 04.05.2012 Palliative Radiotherapy · 2018-02-22 · SRO Tutorial Palliative Care – Palliative Radiotherapy 30 Jacqueline Vock, Universitätsklinik

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 88

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Entscheidungshilfe

Poor prognosis consider stent

otherwise brachytherapy

Steyerberg Gastrointest Endosc 2005

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 90

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 98

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 99

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Scoccianti Radiother Oncol 2012

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 100

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 101

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 102

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 103

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 104

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 105

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 106

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Page 89: SRO Tutorial Palliative Care 04.05.2012 Palliative Radiotherapy · 2018-02-22 · SRO Tutorial Palliative Care – Palliative Radiotherapy 30 Jacqueline Vock, Universitätsklinik

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 89

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Thanks

Questions

Discussion

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 90

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 98

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 99

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Scoccianti Radiother Oncol 2012

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 100

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 101

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 102

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 103

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 104

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 105

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 106

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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SRO Tutorial Palliative Care ndash Palliative Radiotherapy 90

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

References

Palliative care

bull Nccn guidelines palliative care wwwnccnorg

bull Nccn guidelines adult cancer pain wwwnccnorg

Pall RT in general

bull Palliative radiation therapy Konski Semin Oncol 2005 32(2) 156-64

bull Too much too little or just the right amount finding the balance in palliative

radiotherapy Jones Curr Probl Cancer 2011 35 325-36

bull Palliative radiotherapy ndash new approaches Van Oorschot Sem Rad Oncol 2011 38 443-

9

bull Palliative radiotherapy tailored to life expectancy in end-stage cancer patients reality or

myth Gripp Cancer 2010 July 1 3251-6

bull Myth we can tailor palliative care to match life expectancy Reality no we canlsquot Hartsell

Cancer 2010 July 1 3078-9

bull Palliative radiotherapy ndash when is it worth it and when is it not Lutz Cancer J 2010

16(5) 473-82

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 98

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 99

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Scoccianti Radiother Oncol 2012

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 100

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 101

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 102

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 103

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 104

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 105

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 106

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Page 91: SRO Tutorial Palliative Care 04.05.2012 Palliative Radiotherapy · 2018-02-22 · SRO Tutorial Palliative Care – Palliative Radiotherapy 30 Jacqueline Vock, Universitätsklinik

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 91

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Bone metastasis

bull Palliative radiotherapy for bone metastases an ASTRO evidence-based guideline Lutz

IJROBP 2011 79 965-76

bull Update on the systematic review of palliative radiotherapy trials for bone metastases

Chow Clin Oncol (R Coll Radiol) 2012 24(2) 112-24

bull Palliative radiotherapy practice within Western European countries impact of the

radiotherapy financing system Lievens Radiother Oncol 2000 56 289-295

bull Differences in palliative radiotherapy for bone metastases within Western European

countries Lievens Radiother Oncol 2000 56(3)297-303

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 98

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 99

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Scoccianti Radiother Oncol 2012

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 100

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 101

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 102

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 103

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 104

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 105

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 106

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Page 92: SRO Tutorial Palliative Care 04.05.2012 Palliative Radiotherapy · 2018-02-22 · SRO Tutorial Palliative Care – Palliative Radiotherapy 30 Jacqueline Vock, Universitätsklinik

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 92

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Neuropathic pain

bull Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic

pain due to bone metastases (Trans-Tasman Radiation Oncology Group TROG 9605)

Roos Radiother Oncol 2005 75(1)54-63

Metastatic spinal cord compression

bull Direct decompressive surgical resection in the treatment of spinal cord compression

caused by metastatic cancer a randomised trial Patchell Lancet 2005 366 643-8

bull 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression Results

of a phase III randomized multicentre Italian trial Maranzano Radiother Oncol 2009 92

174-9

bull Final results of a prospective study comparing the local control of short-course and long-

course radiotherapy for metastatic spinal cord compression Rades IJROBP 2011

79(2) 524-30

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 98

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 99

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Scoccianti Radiother Oncol 2012

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 100

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 101

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 102

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 103

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 104

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 105

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 106

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Page 93: SRO Tutorial Palliative Care 04.05.2012 Palliative Radiotherapy · 2018-02-22 · SRO Tutorial Palliative Care – Palliative Radiotherapy 30 Jacqueline Vock, Universitätsklinik

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 93

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Brain metastases

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic

brain tumors A randomized study of doses of 4 8 and 16 mg per day

bull Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy

Oncology Group (RTOG) brain metastases trials Gaspar IJROBP 1997 37(4) 745-51

bull Diagnosis-specific prognostic factors indexes and treatment outcomes for patients with

newly diagnosed brain metastases a multi-institutional analysis of 4259 patients

Sperduto IJROBP 2010 77 655-61

bull Treatment of brain metastases review of phase III randomized controlled trials

ScocciantiRicardi Radiother Oncol 2012 102 168-79

bull Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es)

an ASTRO evidence-based guideline Practical Radiation Oncology 2012 in press

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 98

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 99

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Scoccianti Radiother Oncol 2012

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 100

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 101

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 102

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 103

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 104

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 105

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 106

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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SRO Tutorial Palliative Care ndash Palliative Radiotherapy 94

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Hemorrhage

bull Palliative radiotherapy for cervical carcinoma a systematic review Van Lonkhuijzen

Radiother Oncol 98(3)287-91

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull A comparison of two radiotherapy regimens for the treatment of symptoms from

advanced bladder cancer Srinivasan Clin Oncol (R Coll Radiol) 1994 6(1)11-3

Dysphagia

bull Palliative radiation therapy for advanced gastrointestinal cancer Murakami Digestion

2008 77 Suppl 129-35

bull Stent insertion or endoluminal brachytherapy as palliation of patients with advanced

cancer of the esophagus and gastroesophageal junction Results of a randomized

prospective trial Bergquist et al Goumlteborg in Diseases of the Esophagus 2005 18

131-139

bull Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia

from oesophageal cancer multicentre randomised trial Homs Lancet 2004 264 1497-

504

bull Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer a

prognostic model to guide treatment selection Steyerberg Gastrointest Endosc 2005

62 333-40

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 98

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 99

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Scoccianti Radiother Oncol 2012

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 100

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 101

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 102

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 103

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 104

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 105

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 106

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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SRO Tutorial Palliative Care ndash Palliative Radiotherapy 95

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Lung

bull Palliative thoracic radiotherapy for lung cancer a systematic review Fairchild J Clin

Oncol 2008 26 4001-11

bull Palliative thoracic radiotherapy in lung cancer an ASTRO evidence-based clinical

practice guideline Rodrigues Practical Radiation Oncology 2011 1 60-71

bull Palliative endobronchial brachytherapy for non-small cell lung cancer (Review) Cardona

The Cochrane Collaboration 2008

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 98

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 99

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Scoccianti Radiother Oncol 2012

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 100

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 101

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 102

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 103

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 104

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 105

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 106

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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SRO Tutorial Palliative Care ndash Palliative Radiotherapy 96

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 98

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 99

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Scoccianti Radiother Oncol 2012

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 100

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 101

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 102

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 103

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 104

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 105

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 106

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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SRO Tutorial Palliative Care ndash Palliative Radiotherapy 97

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

bull Neurology 1994 Apr44(4)675-80

bull Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain

tumors a randomized study of doses of 4 8 and 16 mg per day

bull Vecht CJ Hovestadt A Verbiest HB van Vliet JJ van Putten WL

bull Source

bull Department of Neuro-Oncology Dr Daniel den Hoed Cancer Center Rotterdam The Netherlands

bull Abstract

bull The purpose of this study was to determine whether lower doses of dexamethasone for treatment of

brain tumor edema are as effective as the conventional dose of 16 mgd We consecutively executed

two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores

of 80 or less In the first series we compared 8 mg dexamethasone per day versus 16 mgd in the

second series 4 mgd versus 16 mgd Standardized evaluation of quality of life and side effects took

place at days 0 7 28 and 56 We randomized a total of 96 patients and evaluated eighty-nine The

Karnofsky score improved in the 8-mg group which had improvement of 80 +- 101 (mean +- SD)

points at day 7 versus 73 +- 142 points in the 16-mg group In the second series the 4-mg group

had improvement of 67 +- 113 points at day 7 and 71 +- 182 points at day 28 versus 91 +- 124

and 56 +- 185 points in the 16-mg group Toxic effects occurred more frequently in the 16-mg group

(p lt 003) We conclude that administration of 4 mg dexamethasone per day for treatment of

brain tumor edema results in the same degree of improvement as does administration of 16

mgd after 1 week of treatment in patients who have no signs of impending herniation Toxic

effects are dose-dependent and during a 4-week period occurred more frequently in patients using

16 mgd(ABSTRACT TRUNCATED AT 250 WORDS)

Role of steroids

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 98

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 99

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Scoccianti Radiother Oncol 2012

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 100

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 101

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 102

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 103

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 104

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 105

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 106

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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SRO Tutorial Palliative Care ndash Palliative Radiotherapy 98

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Gaspar IJROBP 1997

GPA (general prognostic

assessment)

age KPS n BM

extracran dis

Sperduto IJROBP 2008

Sperduto IJROBP 2010

Prognostic indices

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 99

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Scoccianti Radiother Oncol 2012

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 100

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 101

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 102

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 103

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 104

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 105

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 106

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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SRO Tutorial Palliative Care ndash Palliative Radiotherapy 99

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

Scoccianti Radiother Oncol 2012

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 100

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 101

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 102

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 103

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 104

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 105

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 106

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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SRO Tutorial Palliative Care ndash Palliative Radiotherapy 100

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 101

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 102

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 103

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 104

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 105

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 106

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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SRO Tutorial Palliative Care ndash Palliative Radiotherapy 101

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 102

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 103

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 104

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 105

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 106

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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SRO Tutorial Palliative Care ndash Palliative Radiotherapy 102

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SRO Tutorial Palliative Care ndash Palliative Radiotherapy 103

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 104

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 105

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 106

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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SRO Tutorial Palliative Care ndash Palliative Radiotherapy 104

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 105

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

SRO Tutorial Palliative Care ndash Palliative Radiotherapy 106

Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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SRO Tutorial Palliative Care ndash Palliative Radiotherapy 105

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Jacqueline Vock Universitaumltsklinik fuumlr Radio-Onkologie

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