SCTS Education day “Radiotherapy in 2016” Dr Steven Watkins Consultant Clinical Oncologist

Overview Quick basics of Radiotherapy Combination Chemotherapy and Radiotherapy in Stage III disease Radiotherapy in Small Cell lung cancer Ablative radiotherapy in non operable Stage I-IIA New/Current Trials and the Commissioning through Evaluation program (CtE)

Basics of Radiotherapy (RT) 66Gy/30# or 55Gy/20#: what exactly does that mean? Palliative, neo-adjuvant, adjuvant and radical Conformal vs IMRT vs IGRT vs Stereotactic/VMAT/CK

Stage III: ChemoRT vs RT Concurrent ChemoRT (Cis/Vin or Cis/Etop plus 66Gy/33#) Standard of care in appropriate patients 2010 Meta analysis of concurrent chemoRT vs sequential chemo then RT showed 13% reduction in risk of death and 4.5% overall survival benefit (15.1 vs 10.6 5yr OS) Added toxicities (oesphagitis/pnuemonitis), therefore patient selection is important

Stage III: ChemoRT vs RT CHART – 54Gy/36#(3x/day) over 12 days, published 1999, 2 yr survival 29% vs 20% compared to RT alone RT alone in pts not fit enough for above: Historic 5yr OS 10% (though this includes earlier stages) Although a recent study (2015), though small numbers (83) showed pts over 60 yrs old tx with RT alone (total dose over 60Gy) due to being unfit for combination tx had actuarial 2 yr OS of 39% and 3 yr OS of 23% (CSS for lung ca, 2yr 57% and 3 yr 47%)

Palliative RT Still has significant role; 40-50% of all Lung cancer patient initially managed with RT, 90% is with palliative intent (RCR College Guidance 2006) 36-39Gy/12-13# High dose palliative 30Gy/10# 20Gy/5# 17Gy/2# Single 10Gy/# Assessment of PS and tx aims is key!

Small Cell Lung Cancer Limited stage Small Cell Lung Carcinoma (i.e. encompassable in a radical RT field) Concurrent Cis/Etop chemo with RT (starting within 30 days of chemo, i.e. Cycle 2) standard of care. Turrisi paper NEJM 1999: concurrent chemo plus 45Gy/30# (twice daily RT vs once daily) started with cycle 2, improved OS at 2yrs 47% vs 41% and 3 yrs 26% vs 16% Standard of care until.....

Small Cell Lung Cancer CONVERT Trial: chemo as above but standard arm 45Gy/30# twice daily tx vs 66Gy/33# once daily reported at ASCO 2016 od RT non inferior to bd RT plus chemo 2 yr survival 56% vs 51% (bd vs od, non sig), better than reported in previous studies. Toxicities of tx less than previously reported secondary to modern RT techniques. Chemo RT with Cis/Etop plus 66Gy/33# new standard off care.

Small Cell Lung Cancer Prophylactic Cranial Irradiation (PCI) 1999 Study (NEJM - Auperin) 5.4% 3yr survival benefit with PCI in Limited stage disease 2007 Study (NEJM – Slotman) PCI in extensive stage disease, 1 yr reduction in brain mets form 40.4% to 14.6% with subsequent survival improvement

Small Cell Lung Cancer Consolidation thoracic RT in extensive stage SCLCa 2015 (Lancet – Slotman) 30Gy/10# post chemo plus PCI, 1 yr survival no difference (33% vs 28%), however 2 yr survival 13% vs 3%!

Stereotactic Ablative Body Radiotherapy (SABR) Higher dose per fraction and less fractions to T1 and small T2 tumours 2yr local control rates of over 80% Option for non-surgical candidates In future may be an acceptable alternative to surgery for some patients? (SABRTooth Trial: SABR vs Surg in high risk pts –feasibility study recruiting)

UK/NICE SABR Guidelines MDT confirmed diagnosis of NSCLC based on findings of positive histology, positive PET scan or growth on serial CT scan Clinical stages of T1 N0 M0 or T2 (≤5cm) N0 M0 or T3 (≤5cm) N0 M0 Radiologically N2 (CT or PET) but confirmed negative on EBUS or Mediastinoscopy Not suitable for surgery because of medical co-morbidity, lesion is technically inoperable or patient declines surgery after surgical assessment

UK/NICE SABR Guidelines (cont) WHO performance status 0-2 Age ≥ 18 years Peripheral lesions outside a 2cm radius of main airways and proximal bronchial tree. This is defined as 2cm from the bifurcation of the second order bronchus e.g. where the right upper lobe bronchus splits; THE NO FLY ZONE

UK/NICE SABR Guidelines (cont) Bronchus Intermedius RUL Bronchus RLL Bronchus LUL Bronchus LLL Bronchus L Lingula Bronchus RML Bronchus Zone of proximal bronchial tree, the “No Fly Zone”, as defined in RTOG 0236 protocol

SABR Platforms for delivery

Linac VMAT Plan

CyberKnife Plan

Evidence for SABR Studies with Mean ± SD Median available data (range) (range) Overall survival (%) 12 months 15 82.8 ± 11.4 83.0 (52 – 100) 24 months 21 64.5 ± 15.5 65.4 (32 – 91) 36 months 18 57.7 ± 16.0 55.9 (32 – 91) 60 months 9 45.3 ± 20.1 47.0 (18 – 77.5) Cause-specific survival (%) 12 months 7 93.7 ± 2.7 94.0 (88 – 96) 24 months 15 77.3 ± 9.9 82.0 (53.5–88) 36 months 14 72.0 ± 11.9 70.0 (53 - 90.5) 60 months 7 56.9 ± 16.2 50.0 (40 –78) Local control (%) 12 months 8 91.8 ± 3.5 92.0 (85.3 – 96) 24 months 11 86.9 ± 9.7 88.0 (67.9 – 96) 36 months 11 80.6 ± 13.6 84.0 (57 – 95) 48 months 1 89.0 ± 0.0 89.0 (n/a) 60 months 1 86.0 ± 0.0 86.0 (n/a)

Toxicity from Radiotherapy Skin Soreness E45, Aqueous Cream Fatigue Rest, course of steroids Cough Course of steroids, inhalers if wheezy Oesophagitis PPI, Soft Diet, Dietician input Rib Fracture

New trials and CtE CORE – about to open Conventional Care or Radioablation in the treatment of Extracranial metastases (Breast, prostate and NSCLCa) SARON – likely to open late 2016/early 2017 Stereotactic Ablative Radiotherapy for Oligometastatic Non-small Cell Lung Cancer Control Arm: standard treatment alone (platinum-based doublet chemotherapy) Experimental Arm: standard treatment plus radical RT to primary and SABR and/or SRS to metastases Commissioning Through Evaluation (CtE) – NHS Program SABR in various oligometastatic situations including lung and adrenal gland from any primary