Lung Cancer: patient pathways and interventions...Sequential Chemo-radiotherapy in Non-Small Cell...

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 -d.rassl@nhs.net/phn-tr.CambridgeSMP2@nhs.net

➢MesobanK (Pap, Adds) - Tissue, blood and pleural fluid samples in patients with or who are being investigated for Mesothelioma – robert.rintoul@nhs.net

➢LuCID Breath – (Owlstone) Lung Cancer Indicator Detection study (Pap & PCH) – Exhaled biomarkers in patients with / without lung cancer – robert.rintoul@nhs.net

➢SPORT (Pap) - Second Primary Lung Cancer Cohort Study – 2-5 yrs post prev treatment with curative intent for stage I- IIIA primary NSCLC- robert.rintoul@nhs.net

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

NSCLCogary.doherty2@nhs.n

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

Robert.rintoul@nhs.net

streece@nhs.net

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,

david.gilligan@nhs.net

CamBMT2 (CUH; Early Phase**)

Rand phase 2 afatinib

penetration into cerebal mets for

pts undergoing neurosurgical

resection +/- prior low-dose

targeted RT.

richard.baird@addenbrookes.nhs.

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.

scp46@medschl.cam.ac.uk

****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

abigail.hollingdale@nhs.net

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.

robert.rintoul@nhs.net

pasupathy-rajah.sivasothy@nhs.net (CUH &

PCH)

Trapped

lung

Boehringer Ingelheim 1199.223

study (WSH)

Non-interventional biomarker

study in patients with NSCLC

(Adenocarcinoma) eligible for

treatment with Nintedanib

danpatterson@nhs.net

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

richard.baird@addenbrookes.nhs.uk

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

kent.yip@nhs.net

SARON (CUH)

Stereotactic Ablative Radiotherapy for

Oligometastatic Non-small Cell Lung

Cancer. A Randomised Phase III Trial

alexander.martin@nhs.net

ADSCaN (CUH)

A Randomised Phase II study of

Accelerated, Dose escalated,

Sequential Chemo-radiotherapy in

Non-Small Cell Lung Cancer

david.gilligan@nhs.net

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+.

david.gilligan@nhs.net

1st Line

CONFIRM (CUH) – DUE TO CLOSE

Phase III, mesothelioma after

first-line treatment, randomised

to nivolumab or placebo.

gary.doherty2@nhs.net

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

Richard.baird@addenbrookes.nhs.uk

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.

David.gilligan1@nhs.net

CHIRON (CUH, Pap)

Tumour-infiltrating lymphocytes

directed against clonal neoantigens.

Ph1/2a. Resectable (primary) NSCLC

in stage IV patients, PS0-1, ALK-,

EGFR WT

gary.doherty2@nhs.net

ATRiUM (CUH; Early Phase**)

A Phase I Study of gemcitabine and the ATR

inhibitor AZD6738

duncan.Jodrell@addenbrookes.nhs.uk

To discuss open systemic

treatment trials for patients at

CUH, please contact Gary

Doherty before formal referral

to ensure a suitable trial is

available

(gary.doherty2@nhs.net)

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%