lung cancer: patient pathways and interventions...sequential chemo-radiotherapy in non-small cell...
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Lung Cancer: patient pathways and
interventions
Dr Robert Rintoul
Reader in Thoracic Oncology, University of Cambridge
Honorary Consultant Physician, Royal Papworth Hospital
Courtesy of Owlstone Medical
Distribution by stage
Symptoms
Symptomatic patients invariably have advanced disease Cough
Breathlessness
Coughing up blood
Persistent chest infections
Lethargy
Weight loss
Hoarse voice
Chest pains
Many patients with early stage disease have no
symptoms
Risk Factors
Smoking history (80%)
Passive Smoking
Previous asbestos exposure
Age
Family History
Ionizing Radiation
Environmental carcinogens
Radon, chemicals, pollution,
Cambridge Thoracic Oncology
Papworth ‘tertiary’ referral service
Joint Cancer Centre with CUH
Specialist diagnostics/staging
Thoracic surgery
Radiotherapy at CUH
Specialist Mesothelioma Centre
Integrated clinical care and research
CRUK Cambridge Cancer Centre
Popn: 6M
Royal Papworth Thoracic Oncology
1400 referrals per annum:
700 new lung cancers – 40% early stage
80 cases Malignant Pleural Mesothelioma
300 metastatic disease from extra-thoracic primary
320 non-malignant pathology
Each year:
200 undergo surgical resection (Papworth)
110 receive radical (chemo) radiotherapy (CUH)
200 receive palliative chemotherapy (DGHs)
Investigation pathway
CXRUsually performed by primary care
Diagnostic/staging biopsiesBronchoscopy/EBUS/CT guided biopsy
Imaging CT +/- PET-CT
Treatment plan
CT guided biopsy
1 cm GGO
B cell lymphoma
Histology of lung cancer
NSCLC 85%
Squamous 35% (falling)
Adenocarcinoma 40% (rising)
Large cell undifferentiated 10%
SCLC 15% (falling)
Why is accurate staging important?
Choose most appropriate treatment
Predict survival
TNM Classification (8th edition)T
T1
Tumour ≤ 3cm in greatest dimension, surrounded by lung or visceral pelura (1)without bronchoscopic evidence of invasion more proximal than the lobar bronchus (2)
T1a: Tumour ≤ 2cm in greatest dimension
T1b: Tumour > 2cm but ≤ 3cm in greatest dimension
T2
Tumour > 3cm but ≤ 7cm (1) or tumour that-involves main bronchus, ≥ 2cm distal to the carina (2)-invades visceral pleura (3)-associated with atelectasis or obstructive pneumonitis that extends to the hilar region but does not involve the entire lung (4)
T2a: Tumour > 3cm but ≤ 5cm in greatest dimension
T2b: Tumour > 5cm but ≤ 7cm in greatest dimension
Metastasis to ipsilateral peribronchial or hilar nodes
Metastasis to ipsilateral mediastinal or subcarinal nodes
Metastasis to contralateral mediastinal / hilar or scalene / supraclavicular nodes
TNM staging table 8th edition
Treatments
Surgical resection (15%) Stage 1,2
Radical radiotherapy (5-10%) Stage 1,2
Chemoradiotherapy (10-15%) Stage 3a
Palliative treatments (75-80%) Stage 3b, 4 Chemotherapy
Molecularly targeted therapies
Palliative radiotherapy
Active supportive care
Radical radiotherapy options
Useful if patient has limited disease that can be encompassed in a radiotherapy field but,
Does not want an operation
Is not fit for an operation
Limited lung function
Other co-morbidities eg IHD, CVD, PVD
Standard radical radiotherapy 55Gy in 20 fractions over 4 weeks
Stereotactic Ablative Radiotherapy (SABR) 20Gy in 5 fractions
STEREOTACTIC ABLATIVE RADIOTHERAPY
Palliative treatment options
Chemotherapy as primary treatment Not curative; aimed at alleviating symptoms
Improve survival by a few months
Radiotherapy Give 1 or 2 fractions for a specific reason
Haemoptysis, bone pain, brain metastases, skin metastases, SVCO.
Molecular targeted therapies
Squamous cell carcinoma
PDL1 estimation
Non-squamous carcinoma
EGFR sensitizing
EML4-Alk
Ros1
PDL1
Why can’t we offer more patients curative
treatment?
Advanced disease at presentation
Poor performance status/frail
Co-morbidities (IHD, CVA, PVD, Renal impairment)
Poor lung function - COPD
Integrated clinical and research service
Each year 40-50% of Papworth lung cancer patients
enter a clinical study (compared with 10% nationally)
Particular focus on early detection of lung cancer
Cancer Research UK priority
Cambridge designated as an early detection hub
Advanced
disease
1st line
EPIDEMIOLOGY/PREVENTION/SCREENING/QUALITATIVE STUDIES
➢CRUK – Stratified Medicine Programme 2 (Pap, Hinch, Adds, PCH, WSH, Ips, N&N)– Molecular screening programme – retrospective tissue and blood sample [email protected]/[email protected]
➢MesobanK (Pap, Adds) - Tissue, blood and pleural fluid samples in patients with or who are being investigated for Mesothelioma – [email protected]
➢LuCID Breath – (Owlstone) Lung Cancer Indicator Detection study (Pap & PCH) – Exhaled biomarkers in patients with / without lung cancer – [email protected]
➢SPORT (Pap) - Second Primary Lung Cancer Cohort Study – 2-5 yrs post prev treatment with curative intent for stage I- IIIA primary NSCLC- [email protected]
Lung Cancer & Mesothelioma Clinical Trials January 2020
NON SMALL CELL LUNG CANCER MESOTHELIOMASMALL CELL LUNG
CANCER
CANOPY-A (CUH)
Phase 3 rand to
canakinumab (IL1beta
mAb)/placebo post
resection (+/- adj chemo)
for stage II-IIIB NSCLC
et
Any line
Chemothera
py
1st line
** FOR EARLY PHASE STUDIES
PLEASE CONTACT THE EARLY
PHASE TEAM @ ADDENBROOKES
FOR LATEST INFORMATION ON
CURRENT TRIALS
MARS 2 (Pap, PCH)
6 cycles of PemCis vs 6 cycles of
PemCis + (extended) pleurectomy
decortication.
Inc PS0-1, disease confined to 1
hemi-thorax. Exc FEV1 or
Tlco<20%, cardiac, renal or liver
co-morbidities
MATRIX (CUH, Pap) – Phase II multi-
arm, genetic marker-directed, non-
comparative. Inc: NSCLC stage III/IV,
failed ≥1 lines, in SMP2, measureable
disease Exc: Other ca ≤3 yrs,
CamBMT2 (CUH; Early Phase**)
Rand phase 2 afatinib
penetration into cerebal mets for
pts undergoing neurosurgical
resection +/- prior low-dose
targeted RT.
uk
STARTRK2 (CUH; Early
Phase**):Phase 2 of entrectanib
(ALK,ROS1,NTRK1/2/3 inhibitor).
ANY line, ANY histology. PROVEN
alteration in ALK, ROS1, NTRK.
Known rearrangements based on
local testing is ok.
****NTRK1/2/3 ONLY (ALK/ ROS
closed)**** Screening includes
Foundation Medicine genomic
testingResectable brain
mets
Advanced disease
subsequent lines
LLCG Study 15
gemcitabine/carboplatin and
hydroxychloroquine versus
carboplatin/etoposide in stage
IV small cell lung cancer, PS 0-
2
MesoTRAP (Pap, CUH & PCH)
A pilot & feasibility study comparing VAT-PD
with IPC in patients with trapped lung due to
MPM to address recruitment and randomisation
uncertainties and sample size requirements for
a Phase III trial.
[email protected] (CUH &
PCH)
Trapped
lung
Boehringer Ingelheim 1199.223
study (WSH)
Non-interventional biomarker
study in patients with NSCLC
(Adenocarcinoma) eligible for
treatment with Nintedanib
PATRIOT (CUH; Early Phase**)
A Phase I Study to assess the Tolerability, Safety
and Biological Effects of a Specific Ataxia
Telangiectasia and Rad3-Related (ATR) Inhibitor
(AZD6738) as a Single Agent and in Combination
with Palliative Radiation Therapy in Patients with
Solid Tumours
CROWN: Lorlatinib vs
Crizotinib in locally
advanced / metastatic Alk+
NSCLC (Ipswich)
INC: PS 0-2, FFPE tissue
available EXC: Some MSCC,
RT<2/52, major surgery<4/52,
significant ILD, other ca <3yrs,
active infection
SARON (CUH)
Stereotactic Ablative Radiotherapy for
Oligometastatic Non-small Cell Lung
Cancer. A Randomised Phase III Trial
ADSCaN (CUH)
A Randomised Phase II study of
Accelerated, Dose escalated,
Sequential Chemo-radiotherapy in
Non-Small Cell Lung Cancer
Curative
intent/Non
surgical
Atomic Meso (CUH)
Non- Epithelioid.
Phase 2/3 Study in patients with
MPM with Low ASS1 expression to
assess ADI-PEG 20 with PemCis.
Inc: Histo proven Biphasic or
Sarcomatoid, chemo naïve, PS 0-
1, Exc: Rt in 2 weeks prior,
Symptomatic brain/spinal cord
mets, HIV+.
1st Line
CONFIRM (CUH) – DUE TO CLOSE
Phase III, mesothelioma after
first-line treatment, randomised
to nivolumab or placebo.
2nd/3rd line
Basket of Baskets (CUH; Early
Phase**)
Phase II, atezolizumab, advanced
solid tumours. Inc Histo/cyto
confirmation, PS0-1, measureable
disease. Exc. Brain mets, untreated
MSSC
2nd and Sub
lines
Beat Meso (CUH)
Phase III RCT Atezoliumab plus
Bevacizumab and standard
chemo vs Bevacizumab and
standard chemo in advanced MPM
inc: histo confirmed (all
subtypes), non surgical, PS0-1,
life exp >3/12.
CHIRON (CUH, Pap)
Tumour-infiltrating lymphocytes
directed against clonal neoantigens.
Ph1/2a. Resectable (primary) NSCLC
in stage IV patients, PS0-1, ALK-,
EGFR WT
ATRiUM (CUH; Early Phase**)
A Phase I Study of gemcitabine and the ATR
inhibitor AZD6738
To discuss open systemic
treatment trials for patients at
CUH, please contact Gary
Doherty before formal referral
to ensure a suitable trial is
available
1 and 5 yr lung cancer survival Cambridge and
Peterborough Sustainability and Transformation Partnership
Office of National Statistics 2018
Survival data on patients followed up to 2015
Of 44 STPs in England
6th highest 1 year survival – 34.5%
2nd highest 5 year survival – 12.2%