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Brian O’Sullivan MD, FRCPC Department of Radiation Oncology University of Toronto How would we practice today using optimal human resources, technology and techniques ? “Achieving the Achievable” HEAD AND NECK CANCER Radiation Treatment Program Symposium “The Future of Radiation Treatment in the 21 st Century” 2 – 3 March, Toronto

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Page 1: Future Rt Cco (0sullivan)

Brian O’Sullivan MD, FRCPCDepartment of Radiation Oncology

University of Toronto

How would we practice today using optimal human resources, technology and techniques ?

“Achieving the Achievable”

HEAD AND NECK CANCER

Radiation Treatment Program Symposium“The Future of Radiation Treatment in the 21st Century”

2 – 3 March, Toronto

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Overview / Objectives

• What is optimal practice and how do we deliver it in the present human and technology resource environment ?

• Is their a rationale for using approaches requiring more expertise and intensive resources ?

• How difficult is it to implement comprehensive IMRT for head and neck ?

• Some problems in delivering very precise treatment techniques

• Some non-traditional examples of the use of precision radiotherapy techniques (eg IMRT)

• Additional barriers to practice today that conflict with available options

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Treatment Options in HN SCCEarly stage disease (T1 and small T2)

– Single modality treatment (RT vs surgery)– Usually conservative RT regimens 50/20 f – 66/33 f

Intermediate stage disease (large T2; small T3 ‘exophytic’; N1 some N2s)

– Most usual: Radiotherapy +/- chemotherapy or Cetuximab– RT alone is intensified altered fractionation– If surgery performed the majority also need post-op RT (margins,

# nodes, ECE)

Advanced stage disease (large T3; T4; Some N2s and N3)– Most usual: concurrent Chemo-Radiotherapy or RT-Cetuximab– May use composite primary surgery with neck dissection. And

post-op RT (margins, # nodes, ECE) and often Chemo (margins and ECE)

– Functional and cosmetic deficits should be considered

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Approaches to locally advanced Head and Neck Cancer

• MARCH: Meta-Analysis of Radiotherapy in Carcinomas of Head & Neck (n= 6,515 patients)Altered fractionation radiotherapy (RT) improved survival as compared to standard RT: Absolute benefit 3·4%8% using Hyperfractionated RT with augmented dose

Bourhis et al Lancet 2006

• MACH-NC: Meta-Analysis of Chemotherapy in Head & Neck Cancer (n=17,858)Chemotherapy (CT) added to RT, improved survival by 5% 8% using concurrent chemo-RT

Bourhis et al ASCO 2004

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Postop Radiation +/- Cisplatinum Postop Radiation +/- Cisplatinum

NEJM 2004 Head and Neck 2005

Post-operative Adjuvant Treatment of head and neck Cancer

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Examples of Schedules with or without chemotherapyChallenge Multi-phased Single Phase IMRT is the (2Gy / fraction) (variable target fractions)Radiobiology 7 wk course 7 wk course 6 wk course

PTV1 50 Gy in 25 f 56 Gy in 35 f 54 Gy in 30 f ‘Microscopic’ (Cord shield 40 Gy) (No cord shield)

PTV2 70 Gy in 35 f 70 Gy in 35 f 66 Gy in 30 f‘Gross’

PTV3 60 Gy in 30 f 63 Gy in 35 f 60 Gy in 30f<2 cm node **

*Requires cord shielding, electrons, low neck matching (3 or 4 ‘phases’)

**Intermediate dose (PTV3) especially useful for small nodes at the level of the brachial plexus, or for dubious small nodes in the radiology report

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What is optimal ?• Potential to include the Target Objects properly• Spare as much normal tissue as possible, and especially

normal tissues where function is compromised– Critical neurological tissues– Salivary function– Swallowing mechanism– Mandible

• Options for augmentation (combined modality) are numerous (available skills and resources affect choice)

• Several balances in decision-making re: technique– Balance against resources to accomplish– What drives the decision ?

• Inclusion of the target • Avoidance of normal tissues• Accomplish both: “Include and avoid”

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PrescribedDose (Gy)

Median MinimumDose to GTV

% IntendedDose

Phase I 40 38.4 96%

Phase II(cord and brainstem shield)

10 7.3 73%

Phase III(chiasm shield)

10 6.5 65%

Phase IV(High Energyboost)

6 4.0 67%

GTV with dose template(outlined using archived MRI restored from DAT )

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Dose coverage issues:

• Surprisingly good outcome historically with RT alone and 2D planning despite inadequate coverage - about 70-75% control in major centres

• Landmark Intergroup 0099 Chemo-RT had very poor control in the control arm

• May have shown us that concurrent chemotherapy can compensate for inadequate coverage in multicentre setting

• Also potentially cure could be higher if local control more optimal; alternatively some of the effect of chemo may disappear

T4 disease with bulk and normal tissue constraints

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• Many of these patients were treated with concurrent chemotherapy

• Need new approaches to improve systemic outcome

IMRT in NPC

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IMRT significantly better than CRT in terms of parotid sparing, and improved QOL (SF36, EORTC)

25% recovery of pre-RT stimulated parotid flow

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• 70-Gy isodose confomed around the PTV for the gross tumor and 59.4 Gy to the ipsilateral neck

• 54 Gy to contralateral neck PTV

• Simultaneously

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Lee at al 2006

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Lee at al 2006

3-yr actuarial CBRT IMRT P-value

Local progression free 85% 95% 0.17

Regional PF 95% 94% 0.90

Locoregional PF 82% 92% 0.18

Distant–free 85% 86% 0.78

Disease-free 76% 82% 0.57

Overall survival 81% 91% 0.10

Treatment-related death 3 0

Tube dependent (2yr) 21% 4% 0.02

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Improved target coverage in numerous sites

Conventional conformal plan in 2/3 phases

Tissue sparing potential of IMRT

Technical deliveryTechnical delivery

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• Without mucosal dose objective

IMRT will treat a larger amount of mucosa with clinically relevant doses compared to conventional RT

• With dose objectives, the reverse is true

up to 30% reduction in the mucosal volume in the high-dose region compared with conventional RT (p < 0.01).

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Caveats about IMRT for Head and Neck CancerPreliminary Results:Extraneous and unusual/unexpected dose deposition:

“Nausea, Vomiting, and Other Unanticipated Toxicities During IMRT for Head and Neck Squamous Cell Carcinoma”

• Headache• Nausea and vomiting• Hair• Eyes and lacrimal glands• Lips• Larynx• Skin• Mucosa

JW Fan, DI Rosenthal et al 2007: ASTRO / ASCO / AHNS Palm Spring

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“Labored swallowing, prolonged eating times, and the limitedrange of foods that can be swallowed lead to disruptionof relationships and social isolation.”

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Eisbruch et al IJROBP 60(5) 1425,2004

Pretreatment 3 months post XRT/chemo

Standard IMRT Sparing IMRT

50 Gy

50 Gy

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Conclusions:

• Saliva production is affected significantly by radiation,

• but with doses <25–30 Gy, recovery is substantial and returns to pretreatment levels 2 years after RT.

N = 142

• Saliva flow rates +/- stimulation

• 18 months after radiation therapy

• mean doses of 0, 20, 30, and 40 Gy, respectively.

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3 Eras of IMRT Provision at PMH (Full inverse planning)

0

50

100

150

200

250

300

Jan-01 Jan-02 Jan-03 Jan-04 Jan-05 Jan-06

Num

ber o

f pat

ient

s

HesitationImplementation

Accomplisment

600 / yr

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Building an IMRT Factory, Courtesy of Stephen Breen

• ICRU 62• Descriptive

•R2CTV56• Retrospective

audit

• General• Documented• Adapted by

plannersExperience-driven

•Contours (all)•Plan (Physics)•Daily Imaging•(RT unit)

Product:High-volume

Head & Neck IMRT Programme

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Quality Assurance StepsCT Sim

Contours

Planning

Treatment

Volumes AppropriateNomenclature ConsistentProtocols

PatientPositioning

Coverage Doses acceptable

Delivery Acceptable (measurement or secondary calculation)

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This H&N structure nomenclature, contouring guidelines and terminology system was implemented to:

• facilitate multidisciplinary communication between radiation oncologists, planners and physicists

• facilitate quality assurance review of H&N planning

• enable the automation of complex programming tasks within our planning system

• facilitate audit of outcomes

Slide: courtesy John Kim

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GTV CTV70 CTV56

Corresponding PTVs Corresponding PTVs PTV70 PTV70 PTV56PTV56(Planners role)(Planners role)

The Primary The Primary –– the Radiation Oncologistthe Radiation Oncologist’’s Role is to s Role is to Contour the Gross Objects and the Putative microscopic Contour the Gross Objects and the Putative microscopic

risk area and label risk area and label appropriartelyappropriartely

T4a N2c M0 Tongue Base CancerT4a N2c M0 Tongue Base Cancer

Slide: courtesy John Kim

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Rretro

RCTV56R2A3

RretroCTV70

R2A3CTV70

The NeckThe NeckRight neck shown onlyRight neck shown only

Corresponding PTVsCorresponding PTVs RretroPTV70 RPTV56RretroPTV70 RPTV56R2A3PTV70R2A3PTV70

T4a N2c M0 Tongue Base CancerT4a N2c M0 Tongue Base CancerSlide: courtesy John Kim

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Daily Online Setup Correction

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Cone-beam CT Images of the Head & Neck

ConeCone--beam CT datasets fully 3D.beam CT datasets fully 3D.

Permit arbitrary reformatting for interpretation. Permit arbitrary reformatting for interpretation.

WellWell--suited to imagesuited to image--guidance applications.guidance applications.

Exquisite anatomical detail possibleExquisite anatomical detail possible

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Random Uncertainty: weekly cone beam studies

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Planning CT sim Day 1 Day 7

Day 14 Day 21 Day 35

Daily Cone beam images can:

1. Track response

2. Determine dose received

3. Guide adaptation

4. Determine PTVsData from David HwangSimilar data on spinal cordMehrdad Vakilha

NCI – All Ireland - Nov 2006

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Evaluation of a Semi-Automated Segmentation Method for Delineation of Organs at Risk andLymph Node Target Volumes in Head and Neck Radiotherapy PlanningMichael KausPhilips Radiation Oncology Systems, Madison, WI

J. Kim, B. O'Sullivan, A. Mansouri, S. Breen, L. A. Dawson, D. A. JaffrayRadiation Medicine Program, Princess Margaret Hospital, University Health Network University of Toronto, Toronto, ON, Canada

ASTRO 2006

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The potential clinical benefits

A population-based semi-automated segmentation– assist physician contouring of complex

H&N cases– improve efficiency of contouring tasks– facilitate implementation of image-

guided and adaptive RT

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• Ultrasonography used to measure difference (R vs L) in carotid wall thickness (intima-media thickness) in 42 unilaterally irradiated parotid cancer patients.

• 5 had a vascular ischaemic event (3 TIA, 2 infarction) at a median of 11 years (range 5.9–13.1 years) following RT.

• In 4 of these 5, it occurred in the area of the irradiated carotid artery. The mean difference in IMT was 1.1 mm.

• One patient developed cerebral infarction contra-lateral to the side of RT and showed no difference in IMT (0 mm).

Is treating T1 Larynx with IMRT reasonable ?

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Is treating T1 Larynx with IMRT reasonable ?

• Where the target is not compromised• Where normal tissues can be spared• Why not place the dose where you want it ?• Potential gains: carotid protection; arytenoid protection

50 Gy 50 Gy

Traditional Volume (IMRT planned) Optimal Volume (IMRT planned)

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Is treating BCC with IMRT reasonable ?

• Where the target is not compromised• Where normal tissues can be spared• Why not place the dose where you

want it ?• Potential gains: Eye preservation

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Patient is ANED at 5 years. Has a small cataract

Is treating BCC with IMRT reasonable ?

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The Role of PET:• Staging / assessment• Prediction (probably

need more than FDG)• Determination of

Response

Pre-chemo RT

• 8 wks post chemo-RT

• Anatomic imaging negative

• Neck dissection positive in 4 nodes

• ANED 3 years later

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Observer variability CT, CECT, PETCET • Do observers draw the same volumes on

CT and CT-PET?– 8 observers (6 RO, 2 NR)– 10 H&N patients– GTVs on CECT, CT-PET, CT– Involved nodes

Findings:

• Specialty makes no difference

• We cannot confirm the perception that FDG-PET reduces uncertainty in primary tumor target volume delineation

• Differences are small, overwhelmed by inter-observer differences

• Lymph node delineation may be facilitated

• Suspicion – PET aids concurrence

CECT PETCT

De Silva S et al ASTRO 2005 and 2006

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A Phase III Study of Radiotherapy ± Cetuximab (C225) in Patients with Locally Advanced HNSCC

Bonner et al NEJM 2006

Months

Local-Regional Control

Prob

abili

ty

RT + C

RT

RT+C21190

36 m69%56%

RT213105

19 m59%48%

PatientsEventsMedian1-Year2-YearLog rank p 0.02

Months

Survival

Pro

babi

lity

RT + C

RT

RT+C21193

54 m62%57%

RT213117

28 m55%44%

PatientsEventsMedian2-Year3-YearLog rank p 0.02

Subgroup analyses (HR):

• 26% rc’d once-daily fractionation = 1.01

• 18% twice-daily fractionation = 0.74

• 56% concomitant boost radiotherapy = 0.64.

RT RT-E

Any Gd 3-4 Any Gd 3-4

Skin 91 18 97 34Mucositis 93 52 91 54Dysphagia 63 30 64 25

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How should we practice ?

• Use Level 1 evidence based ev evidence for dose fractionation regimen

• Concerning Technique– Do not compromise on the targets– Spare the normal tissues when this is possible

• Place the dose where you want it and where it needs to go

• Often that means IMRT in complex Head and Neck cancers

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Planning & Treatment Team• Radiation Oncology

– A. Bayley, B. Cummings, L Dawson, J. Kim, B. O’Sullivan, J. Ringash, J. Waldron

• Physicists– S. Breen, J. Borg, A. Damyanovich, B. Zhang

• Team 1 Planners– J.Roussos, M.Ryan, D.Sajac, I Kaminsky, S.Pillay, S.Pizzale,

C.Rocca, L.Chau, P. Rakaric, S.Singh, M.Glinnyi, J.Giovinazzo

• Therapists (33)– S.Singh, S. Pizzale, I.Kaminsky, C. Rocca, L.Chau, P. Rakaric

C.Bradley, E.Borodina, C.Cerase, C.Chow, C.Dupuis, M.Engel, C.Field, A.Fung, J.Giovinazzo, M.Glinnyi, B.Guibord,, S.Hua, S.Huang, J.Loudon, L.Johnson, K.Man, D.Marshall, , E.Mettrick,G.Parlan, S.Pillay, F.Sie , W.So, A.Sperdutti, M.Tamerou, W.Tang, V.Truong, G.Wu

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Additional Key Team Members

Image Management

David JaffrayMichael Sharpe Jeff SiewerdsenBern NorrlingerTing Jun ZhangDoug MoseleyAnna KirilovaKristy Brock

Medical Imaging

Ann KellerEugene Yu

RMP IT Infrastructure

Terry MichaelsonStuart Rose and team

Medical OncologyLillian SiuEric Chen

Translational Science

Fei-Fei LiuCarlo BastianuttoAngelo HuiSizanne Kame-Reid

Pathology

Bayardo Perez- Ordonez

The Susan Grange Family Bartley-Smith/Wharton Fund of the PMH Foundation

CARO/ACURA Fellowship ProgramElekta Oncology SystemsVarian Medical Systems

Head and Neck Surgery

Pat GullaneRalph GilbertJon IrishDale BrownIan WitterickJerry FreemanPeter Neligan

Nursing, Nutrition, Psycho-social

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