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Michael Brada Torino 6 March 2015 Perspectives in lung cancer Stereotactic ablative radiation therapy (SABR) in patients with inoperable NSCLC.

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Presentation on theme: "Michael Brada Torino 6 March 2015 Perspectives in lung cancer Stereotactic ablative radiation therapy (SABR) in patients with inoperable NSCLC."— Presentation transcript:

1 Michael Brada Torino 6 March 2015 Perspectives in lung cancer Stereotactic ablative radiation therapy (SABR) in patients with inoperable NSCLC

2 SABR in the context of modern radiotherapy of NSCLC SABR in localised NSCLC uncertaintieswhat is it alternativesefficacy

3 SABR in the context of modern radiotherapy of NSCLC SABR in localised NSCLC uncertaintieswhat is it alternativesefficacy

4 SABR in the context of modern radiotherapy of NSCLC SABR in localised NSCLC uncertaintieswhat is it alternativesefficacy

5 SABR in the context of modern radiotherapy of NSCLC SABR in localised NSCLC

6 Deconstructing SABR  High precision  Conformal  High dose  Hypofractionated High precision localised radiotherapy SABR – what is it?

7 Deconstructing SABR  High precision  Conformal  High dose  Hypofractionated Technology High precision localised radiotherapy SABR – what is it?

8 Requirements of high precision High precision localised radiotherapy for NSCLC  accurate definition of target  accurate delivery

9 staging tumour margin effect of motion Accurate target localisation define tumour extent

10 staging tumour margin effect of motion Accurate target localisation define tumour extent

11 Requirements of high precision High precision localised radiotherapy for NSCLC  accurate definition of target  accurate delivery

12 Localised delivery of SABR multiple non-coplanar fixed fields arcing IMRT (VMAT/RapidArc/Tomotherapy) robotic mounted linac (cyberknife) High precision localised radiotherapy for NSCLC

13 % reported studies% patients Meta-analysis of SABR for stage I NSCLC Technology used for delivery of SABR Linac Cyberknife Linac or Cyberknife Tomotherapy Body GK Linac Cyberknife Linac or Cyberknife Tomotherapy Body GK 76% 86% Solda, Lodge, Ashley, Whitington, Goldstraw & Brada 2013; Radiother Oncol, 109, 1-7 Linac – linear accelerator, GK – gamma knife, Cyberknife – robotic arm mounted small linac

14 2 year local control Meta-analysis of SABR for stage I NSCLC – delivery technology individual datasummary 91% 88% LinacCyberkife Solda, Lodge, Ashley, Whitington, Goldstraw & Brada 2013; Radiother Oncol, 109, 1-7 Linac – linear accelerator, Cyberknife – robotic arm mounted small linac

15 2 year survival Meta-analysis of SABR for stage I NSCLC – delivery technology individual datasummary Solda, Lodge, Ashley, Whitington, Goldstraw & Brada 2013; Radiother Oncol, 109, 1-7 69% 73% Linac – linear accelerator, Cyberknife – robotic arm mounted small linac

16 Deconstructing SABR  High precision  Conformal  High dose  Hypofractionated Biology SABR – what is it?

17 Phase I/II Locally advanced NSCLC increasing RT dose (related to normal lung DVH) Improving lung cancer radiotherapy Radical radiotherapy – dose escalation

18 Dose response in non-small cell lung cancer (NSCLC) Summary of published phase I/II studies (1201 patients, 8 publications) 2 year local progression free survival (corrected for stage distribution) Fenwick model (solid curve) ● conventional fractionation corrected for dose fractionation/time and stage distribution Partridge, Ramos, Sardaro & Brada 2011, Radioth Oncol 99, (1) 6 -11

19 early stage disease Fenwick model (solid curve) localised disease locally advanced disease Dose response in non-small cell lung cancer (NSCLC) Summary of published phase I/II studies including SABR 2 year local progression free survival ● conventional fractionation ∆ hypofractionated SABR Partridge, Ramos, Sardaro & Brada 2011, Radioth Oncol 99, (1) 6 -11

20 Dose response in non-small cell lung cancer (NSCLC) Summary of published phase I/II studies including SABR 2 year local progression free survival (corrected for stage distribution) Fenwick model (solid curve) localised disease locally advanced disease ● conventional fractionation ∆ hypofractionated SABR Partridge, Ramos, Sardaro & Brada 2011, Radioth Oncol 99, (1) 6 -11

21 Tumour size and disease control Werner-Wasik et al 2008 Int. J. Radiation Oncology Biol Phys, 70, (2), 385–390 RTOG 93-11 Phase I/II dose escalation study in NSCLC 45cm 3 ≈ 4.5 cm diameter sphere time (months) % progression free survival smaller tumours ≤45cm 3 larger tumours >45cm 3

22 Dose response in non-small cell lung cancer (NSCLC) Summary of published phase I/II studies including SABR 2 year local progression free survival (corrected for stage distribution) Fenwick model (solid curve) localised disease locally advanced disease ● conventional fractionation ∆ hypofractionated SABR Partridge, Ramos, Sardaro & Brada 2011, Radioth Oncol 99, (1) 6 -11

23 Local control vs dose in SABR v an Baardwijk et al 2012 Radioth Oncol 105, 145–149 Dose comparison of SABR & accelerated RT freedom from local progression at 3 years local control in stage I NSCLC

24 SABR in the context of modern radiotherapy of NSCLC  accurate definition of tumour extent  dose fractionation Current uncertainties

25 Deconstructing SABR  High precision  Conformal  High dose  Hypofractionated High precision localised radiotherapy SABR – what is it?

26 Deconstructing SABR  High precision  Conformal  High dose  Hypofractionated High precision localised radiotherapy SABR – what it is NOT stereotactic ablative

27 SABR in the context of modern radiotherapy of NSCLC SABR in localised NSCLC uncertaintieswhat is it alternativesefficacy

28 SABR in the context of modern radiotherapy of NSCLC SABR in localised NSCLC uncertaintieswhat is it alternativesefficacy

29 Local progression free survival (%) local control survival Survival (%) Endpoints of efficacy of SABR in stage I NSCLC SABR for stage I NSCLC Tumour control Verstegen et al 2011 Radiother Oncol 101, 250–254 VU Amsterdam 591 patients ➞ histol. verified ➞ histol. unverified

30 Endpoints of efficacy of SABR in stage I NSCLC 6.9.13 22.1.15 Tumour control SABR for stage I NSCLC

31 Endpoints of efficacy of SABR in stage I NSCLC Local progression free survival (%) Verstegen et al 2011 Radiother Oncol 101, 250–254 SABR for stage I NSCLC local control survival Survival (%) Tumour control Survival VU Amsterdam 591 patients ➞ histol. verified ➞ histol. unverified

32 SABR in the context of modern radiotherapy of NSCLC SABR in localised NSCLC uncertaintieswhat is it alternativesefficacy survival quality of life

33 SABR and quality of life (QOL) Laagerwaard et al 2012 J Thor Oncol, 7, (7); 1148-1194 Quality of life after SABR (EORTC QLQ C30) Change in global QOL score

34 Management options in localised NSCLC Surgery Conventional radiotherapy SABR Radiofrequency ablation Alternatives

35 Management options in localised NSCLC Surgery Conventional radiotherapy SABR Radiofrequency ablation Alternatives

36 SABR for localised NSCLC Meta-analysis of published results January 2006 – June 2012 published SABR studies in early stage NSCLC data on 2 yr survival & local control no. studies (patients) systematic review45 (3201) Solda, Lodge, Ashley, Whitington, Goldstraw & Brada 2013 Radiother Oncol, 109, 1-7

37 SABR for localised NSCLC Meta-analysis of published results January 2006 – June 2012 2456 initial search 756 duplicates removed 134 clinical studies 837770676257 NSCLC analysable early stage available outcome information 2 year survival available staging available Solda, Lodge, Ashley, Whitington, Goldstraw & Brada 2013 Radiother Oncol, 109, 1-7

38 2456 initial search 756 duplicates removed 134 clinical studies 837770676257 NSCLC analysable early stage available outcome information 2 year survival available staging available manuscript 57 45 duplicates removed Meta-analysis of published results January 2006 – June 2012 SABR for localised NSCLC Solda, Lodge, Ashley, Whitington, Goldstraw & Brada 2013 Radiother Oncol, 109, 1-7

39 Meta-analysis of SABR for stage I NSCLC 2 year local control individual datasummary Solda, Lodge, Ashley, Whitington, Goldstraw & Brada 2013 Radiother Oncol, 109, 1-7

40 Meta-analysis of published results January 2006 – June 2012 SABR for localised NSCLC Comparative group IASLC cohort 1990 - 2000 Groome et al 2009 Survival (%) IA IB IASLC – International Association for the Study of Lung Cancer

41 2 year survival Meta-analysis of SABR for stage I NSCLC individual data 3201 patients summary 70% 68% SABRsurgery Solda, Lodge, Ashley, Whitington, Goldstraw & Brada 2013 Radiother Oncol, 109, 1-7

42 Management options in localised NSCLC Surgery Conventional radiotherapy SABR Radiofrequency ablation Alternatives

43 Comparison of surgery & SABR in stage I NSCLC propensity matched – SABR vs lobectomy SEERS - Medicare 2001 – 07 10,923 patients with stage IA & IB NSCLC, aged >65 Shirvani et al 2013 Int J Radiation Oncol Biol Phys, 84, (5), 1060-1070

44 Management options in localised NSCLC Surgery Conventional radiotherapy SABR Radiofrequency ablation Alternatives

45 Zheng et al 2014 Int J Radiation Oncol Biol Phys; 90, (3), 603-611, Comparison of surgery & SABR in stage I NSCLC meta-analysis of published studies 40 SABR studies (4850 pts) and 23 surgery studies (7071 patients) surgery IA SABR IA SABR IB surgery IB survival

46 Zheng et al 2014 Int J Radiation Oncol Biol Phys; 90, (3), 603-611, Comparison of surgery & SABR in stage I NSCLC meta-analysis of published studies 40 SABR studies (4850 pts) and 23 surgery studies (7071 patients) survival and operability (lobectomy) (limited lung resection)

47 Zheng et al 2014 Int J Radiation Oncol Biol Phys; 90, (3), 603-611, Comparison of surgery & SABR in stage I NSCLC meta-analysis of published studies 40 SABR studies (4850 pts) and 23 surgery studies (7071 patients) survival and age (lobectomy) (limited lung resection)

48 Comparison of surgery & SABR in stage I NSCLC propensity matched – SABR vs lobectomy SEERS - Medicare 2001 – 07 10,923 patients with stage IA & IB NSCLC, aged >65 Shirvani et al 2013 Int J Radiation Oncol Biol Phys, 84, (5), 1060-1070

49 Comparison of surgery & SABR in stage I NSCLC propensity matched – SABR vs sublobar resection SEERS - Medicare 2001 – 07 10,923 patients with stage IA & IB NSCLC, aged >65

50 Management options in localised NSCLC Surgery Conventional radiotherapy SABR Radiofrequency ablation Alternatives

51 Dose response in non-small cell lung cancer (NSCLC) Summary of published phase I/II studies including SBRT 2 year local progression free survival (corrected for stage distribution) Fenwick model (solid curve) localised disease locally advanced disease ● conventional fractionation ∆ hypofractionated SBRT Partridge, Ramos, Sardaro & Brada 2011, Radioth Oncol 99, (1) 6 -11

52 Local control vs dose in SABR van Baardwijk et al 2012 Radioth Oncol 105, 145–149 Dose comparison of SABR & accelerated RT freedom from local progression at 3 years local control in stage I NSCLC

53 Shirvani et al 2013 Int J Radiation Oncol Biol Phys, 84, (5), 1060-1070 Comparison of conventional RT & SABR in stage I NSCLC propensity matched – SABR vs conventional RT SEERS - Medicare 2001 – 07 10,923 patients with stage IA & IB NSCLC, aged >65

54 Management options in localised NSCLC Surgery Conventional radiotherapy SABR Radiofrequency ablation Alternatives

55 Alternatives to SABR in localised NSCLC radiofrequency ablation (RFA) Simon et al 2012 Europ J Radiol 81, 4167 survival probability 2 yrs 82 patients stages I, II, III (9%) (Brown University, Providence) 62%

56 Alternatives to SABR in localised NSCLC radiofrequency ablation & comorbidity CCI – Charleson Comorbidity Index CCI = 5+ CCI = 3-4 CCI = 1-2 survival probability Simon et al 2012 Europ J Radiol 81, 4167

57 RFASABR 5 year local control58 – 68%83 – 90% 3 year survival47 – 74%38 – 85% morbidity33 – 100%3 – 38% Renaud et al 2013 Interactive CardioVascular and Thoracic Surgery 16, 68–73 Comparison of RFA & SABR in NSCLC review of literature RFA – radiofrequency ablation SABR – stereotactic ablative body radiotherapy

58 SABR in the context of modern radiotherapy of NSCLC SABR in localised NSCLC uncertaintieswhat is it alternativesefficacy

59 Deconstructing SABR  High precision  Conformal  High dose  Hypofractionated High precision localised radiotherapy Technology Biology SABR – what is it? Renaud et al 2013 Interactive CardioVascular and Thoracic Surgery 16, 68–73

60 Deconstructing SABR  High precision  Conformal  High dose  Hypofractionated High precision localised radiotherapy Technology Biology SABR – future “The end of the beginning or the beginning of the end?” Brada, Pope & Baumann 2015 Radiotherapy & Oncology (epub)

61 Lung cancer in England and Wales I II III IV nk Stage distribution of lung cancer CR UK cancer statistics - England & Wales 2012

62 Perspectives in lung cancer Stereotactic ablative radiation therapy (SABR) in patients with inoperable NSCLC Michael Brada BSc, MB ChB, FRCP, FRCR, DSc Professor of Radiation Oncology University of Liverpool Department of Molecular and Clinical Cancer Medicine & Department of Radiation Oncology Clatterbridge Cancer Centre NHS Foundation Trust Bebington, Wirral, CH63 4JY michael.brada@liverpool.ac.uk

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