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 yr 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. 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

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 ± (52 – 100)
24 months ± (32 – 91)
36 months ± (32 – 91)
60 months ± (18 – 77.5)
Cause-specific survival (%)
12 months ± (88 – 96)
24 months ± (53.5–88)
36 months ± ( )
60 months ± (40 –78)
Local control (%)
12 months ± (85.3 – 96)
24 months ± (67.9 – 96)
36 months ± (57 – 95)
48 months ± (n/a)
60 months ± (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