SCTS Education day “Radiotherapy in 2016”

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

2. 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)

3. 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

4. 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

5. 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%)

6. 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!

7. 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.....

8. 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.

9. 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

10. 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%!

11. 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)

12. 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

13. 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

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

15. SABR Platforms for delivery

16. Linac VMAT Plan

17. CyberKnife Plan

18. 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)

19. 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

20. 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