Lung Cancer : Lung Cancer : Lung Cancer : Lung Cancer : Improving - PowerPoint PPT Presentation

Lung Cancer : Lung Cancer : Lung Cancer : Lung Cancer : Improving the Cure Rate Improving the Cure Rate with Radiation with Radiation ith R di ti ith R di ti Andrea Andrea Bezjak Bezjak , MDCM, MSc, FRCPC The Addie MacNaughton Chair in Thoracic Radiation Oncology

Outline of Presentation Outline of Presentation Outline of Presentation Outline of Presentation • Management of Lung Cancer –Changes in the past 20 yrs –Evidence of progress –Evidence of progress –Contribution of RT to improving cure rate of lung cancer lung cancer –Current efforts at improving cure even further

Back in 1988 Back in 1988 Back in 1988…. Back in 1988….

Back in 1988 Back in 1988 Back in 1988…. Back in 1988….

Back in 1988… Back in 1988… Back in 1988 Back in 1988

Management of Lung Cancer in 1988 Management of Lung Cancer in 1988 g g g g • Lung ca is systemic disease – needs better systemic treatment t i t t t • Best to use only one modality

Back in 1988 Back in 1988 Back in 1988… Back in 1988… The Tools The Tools: Diagnosis = CT, mediastinoscopy RT planning = RT planning Planning CT Correction for lung tissue g Fluoroscopy RT treatment = Cobalt or Linac F/U F/U = CXR CXR no MRIs

Traditional RT Treatment Plans Traditional RT Treatment Plans Traditional RT Treatment Plans Traditional RT Treatment Plans

RT alone vs chemoRT RT alone vs chemoRT for stage III NSCLC for stage III NSCLC for stage III NSCLC for stage III NSCLC –Dillman et al NEJM 1992 Dillman et al NEJM 1992 • Sequential chemotherapy and RT –Schaake-Koning et al NEJM 1992 Schaake Koning et al NEJM 1992 • Concurrent daily or weekly cisplatin –And many others…..

Dillman et al NEJM 1992 Dillman et al NEJM 1992 Dillman et al NEJM 1992 Dillman et al NEJM 1992

Schaake Schaake- -Koning et al 1992 Koning et al 1992 Overall Survival Overall Survival Overall Survival Overall Survival

Schaake Schaake- -Koning et al 1992 Koning et al 1992 Local Local-Recurrence Free Survival Local Local-Recurrence Free Survival Recurrence Free Survival Recurrence Free Survival

Locally Advanced NSCLC-1990s Locally Advanced NSCLC-1990s Sequential Chemo-RT Improves Survival q p Compared to RT Alone 2YR O 2YR Overall Survival ll S i l Trial Pts. RT CTRT Finnish Fi i h 238 238 17% 17% 19% 19% NCCTG 107 16% 21% CALGB CALGB 155 155 13% 13% 26% 26% IGR-French 331 14% 21%

Long Term Survival Comparison between Long Term Survival Comparison between Sequential and Concurrent Chemoradiation Sequential and Concurrent Chemoradiation q Therapy Therapy RTOG 9410 RTOG 9410 WJLCG WJLCG 21 21 19 19 % 21 % 21 % 17 19 % 19 % 17 r OS r OS OS OS 15 15 % 5 yr % 5 yr % 4 yr % 4 yr 13 13 13 13 11 11 % 9 9 9 9 % 12 % 12 % 9 % 9 % 7 7 5 5 Sequential Concurrent Sequential Concurrent

Survival Comparison between Sequential Survival Comparison between Sequential and Concurrent Chemoradiation Therapy and Concurrent Chemoradiation Therapy and Concurrent Chemoradiation Therapy and Concurrent Chemoradiation Therapy 24 22 22 P < 0.05 (Kruskal P < 0.05 (Kruskal- -Wallis Test) Wallis Test) WJLCG 20 ival GLOT 17 ( 17 (n=709) 17 (n=709) 17 ( 709) 709) an surv 18 CZECH LAMP 16 16 media 14 (n=716) 14 (n=716) RTOG 9410 14 BROCAT BROCAT 12 10 10 Sequential Concurrent

Survival Improvement in Stage III Survival Improvement in Stage III NSCLC since 1980’s NSCLC since 1980’s NSCLC since 1980’s NSCLC since 1980’s 17.7 17 7 17 7 17.7 19 CALBG Finsih 17 IGR IGR l survival 13.8 13.8 15 NCCTG WJLCG 13 GLOT GLOT edian s CZECH 9.8 9.8 11 LAMP RTOG 9410 RTOG 9410 9 9 m MUNICH 7 ECOG 2597 5 1980's 1990's 2000's

Early Toxicity Comparison between Early Toxicity Comparison between Sequential and Concurrent Chemoradiation Sequential and Concurrent Chemoradiation q 30 Therapy Therapy 25 25 23% 23% G3/4) WJLCG 20 20 agitis (G GLOT CZECH 15 Esopha LAMP LAMP 10 RTOG 9410 % E BROCAT 4% 4% 5 0 Sequential Concurrent

Early and Late Toxicity Comparison between Early and Late Toxicity Comparison between Sequential and Concurrent Chemoradiation Sequential and Concurrent Chemoradiation Sequential and Concurrent Chemoradiation Sequential and Concurrent Chemoradiation Therapy in RTOG 9410 Therapy in RTOG 9410 is is 45 45 monitis s monitis umonit umonit 40 40 35 35 Pneu Pneu Pneu Pneu 30 30 25 25 20 20 15 15 10 10 10 10 5 5 0 0 Sequential Conc D Conc BID Sequential Conc D Conc BID Early Toxicity Early Toxicity Late Toxicity Late Toxicity

Improving Cure Rates Improving Cure Rates Improving Cure Rates Improving Cure Rates • Is improved survival only due to Is improved survival only due to chemotherapy? • Can improved survival also be achieved by improvements in RT?? by improvements in RT??

CHART for stage III NSCLC CHART for stage III NSCLC CHART for stage III NSCLC CHART for stage III NSCLC • 54 Gy/1.2 Gy per fraction tid (6-8 hrs apart) 54 Gy/1.2 Gy per fraction tid (6 8 hrs apart) • Started on a Monday • Pts treated continuously (including Sat and Pts treated continuously (including Sat and Sunday) till next Friday • Overall treatment duration 12 days O 12 • No chemo given

RCT of CHART vs Conventional RT RCT of CHART vs Conventional RT RCT of CHART vs Conventional RT RCT of CHART vs Conventional RT • Saunders et al, Lancet 1997 • 54 Gy/1.2 Gy tid/12 d vs 60 Gy/30 fr/ 6 w • Almost 600 pts p • Results: CHART 60 Gy/30fr – median survival – median survival 16.5 mo 16 5 mo 13 mo 13 mo – 2 yr OS 30% 21% – 3 yr OS 3 yr OS 20% 20% 13% 13% B Best results for squamous cell t lt f ll

Saunders et all, CHART vs 60/30 CHART Conventional RT

Saunders et all, CHART vs 60/30 Conventional CHART RT

Belani et al, JCO 2005

Belani et al, JCO 2005

Belani et al, JCO 2005

Outline of Presentation Outline of Presentation Outline of Presentation Outline of Presentation • Management of Lung Cancer –Changes in the past 20 yrs –Evidence of progress –Evidence of progress –Contribution of RT to improving cure rate of lung cancer lung cancer –Current efforts at improving cure even further

Management of Lung Cancer in 2008 Management of Lung Cancer in 2008 • Multi-modality approach • N2 = chemo RT or in selected cases chemoRT surgery • N3 = chemoRT

Currently Currently Currently Currently – in 2008 in 2008 in 2008… in 2008… The Tools: Diagnosis = CT, mediastinoscopy, Di i CT di ti EBUS, PET RT planning = 4D CT, PET CT IMRT RT treatment = Image guidance CBCT F/U = CXR, CTs consideration of salvage Rx consideration of salvage Rx

Target Definition using FDG PET Target Definition using FDG PET Target Definition using FDG PET Target Definition using FDG PET

Currently Currently Currently Currently – in 2008 in 2008 in 2008… in 2008… The Tools: Diagnosis = CT, mediastinoscopy, Di i CT di ti EBUS, PET RT planning = 4D CT, PET CT IMRT RT treatment = Image guidance CBCT F/U = CXR, CTs consideration of salvage Rx consideration of salvage Rx

4D-CT planning scan 4D CT planning scan Block (with 2 Markers) place on Patient Block (with 2 Markers) place on Patient RPM System on GE Scanner R e tro s p e c tiv e 4 D -C T im a g in g R e s p ira tio n W a v e fo rm fro m R e s p ira tio n W a v e fo rm fro m R P M R e s p ira to ry G a tin g S ys te m In h a la tio n E x h a la tio n “Im a g e a c q u ire d ” sig n a l to R P M sig n a l to R P M sys te m X -ra y o n T h ird c o u c h p o s itio n F irs t c o u ch p o sitio n S e c o n d c o u c h p o s itio n T ins u T ins u P a n P a n Phase Encoding & Image Acquisition

Currently Currently Currently Currently – in 2008 in 2008 in 2008… in 2008… The Tools: Diagnosis = CT, mediastinoscopy, Di i CT di ti EBUS, PET RT planning = 4D CT, PET CT IMRT RT treatment = Image guidance CBCT F/U = CXR, CTs consideration of salvage Rx consideration of salvage Rx

IMRT (Intensity Modulated RT) IMRT (Intensity Modulated RT) IMRT (Intensity Modulated RT) IMRT (Intensity Modulated RT) • Multiple fields Multiple fields • Intensity across field varies • Thus, dose to the target can be more Thus dose to the target can be more precisely planned, while avoiding organs at risk organs at risk • Allows dose escalation

Conventional 3D treatment planning Conventional 3D treatment planning Conventional 3D treatment planning Conventional 3D treatment planning

Currently Currently Currently Currently – in 2008 in 2008 in 2008… in 2008… The Tools: Diagnosis = CT, mediastinoscopy, Di i CT di ti EBUS, PET RT planning = 4D CT, PET CT IMRT RT treatment = Image guidance CBCT F/U = CXR, CTs consideration of salvage Rx consideration of salvage Rx

Limitations of Traditional Portal Imaging Portal Imaging Portal image from RT unit DRR of the field Based on Planning CT

Planning CT Planning CT Green line outlines tumor (GTV) ( ) Blue line outlines PTV (GTV + margin)