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 ith R di ti ith R di ti with Radiation with Radiation

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

t i t t t systemic treatment

• 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 CXR F/U = 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 Recurrence Free Survival Local Local-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 ll S i l 2YR Overall Survival Trial Pts. RT CTRT Fi i h 238 17% 19% Finnish 238 17% 19% NCCTG 107 16% 21% CALGB 155 13% 26% CALGB 155 13% 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

19 21

WJLCG WJLCG

19 21

RTOG 9410 RTOG 9410 %

13 15 17

OS OS 19 % 19 %

13 15 17

r OS r OS 21 % 21 %

9 11 13

% 5 yr % 5 yr

9 11 13

% 4 yr % 4 yr %

5 7 9

% 9 % 9 %

5 7 9

12 % 12 %

Sequential Concurrent Sequential Concurrent

Survival Comparison between Sequential Survival Comparison between Sequential and Concurrent Chemoradiation Therapy and Concurrent Chemoradiation Therapy

22 24

and Concurrent Chemoradiation Therapy and Concurrent Chemoradiation Therapy

20 22

ival

WJLCG GLOT

17 ( 709) 17 ( 709)

P < 0.05 (Kruskal P < 0.05 (Kruskal-

• Wallis Test)

Wallis Test)

16 18

an surv

CZECH LAMP

17 (n=709) 17 (n=709)

14 16

media

RTOG 9410 BROCAT

14 (n=716) 14 (n=716)

10 12 BROCAT 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 19

l

CALBG Finsih IGR

17.7 17.7

13 15

survival

IGR NCCTG WJLCG GLOT

13.8 13.8

9 11

edian s

GLOT CZECH LAMP RTOG 9410

9.8 9.8

7 9

m

RTOG 9410 MUNICH 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

25 30

q Therapy Therapy

20 25

G3/4)

WJLCG GLOT

23% 23%

15 20

agitis (G

CZECH LAMP

10

Esopha

LAMP RTOG 9410

5

% E

BROCAT

4% 4%

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

45

is is

45

s

35 40

umonit umonit

35 40

monitis monitis

25 30

Pneu Pneu

25 30

Pneu Pneu

10 15 20 10 15 20 5 10 5 10

Sequential Conc D Conc BID

Early Toxicity Early Toxicity

Sequential Conc D Conc BID

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 O 12

• Overall treatment duration 12 days
• 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 16 5 mo 13 mo – median survival 16.5 mo 13 mo – 2 yr OS 30% 21% 3 yr OS 20% 13% – 3 yr OS 20% 13% B t lt f ll Best results for squamous cell

Saunders et all, CHART vs 60/30

CHART Conventional RT

Saunders et all, CHART vs 60/30

CHART Conventional 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 – in 2008 in 2008 Currently Currently in 2008… in 2008…

The Tools: Di i CT di ti Diagnosis = CT, mediastinoscopy, 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 – in 2008 in 2008 Currently Currently in 2008… in 2008…

The Tools: Di i CT di ti Diagnosis = CT, mediastinoscopy, 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 s p ira tio n W a v e fo rm fro m

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 P M R e s p ira to ry G a tin g S ys te m

E x h a la tio n In h a la tio n “Im a g e a c q u ire d ” sig n a l to R P M X -ra y o 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 h ird c o u c h p o s itio n sig n a l to R P M sys te m

T ins u T ins u P a n P a n

Phase Encoding & Image Acquisition

Currently Currently – in 2008 in 2008 Currently Currently in 2008… in 2008…

The Tools: Di i CT di ti Diagnosis = CT, mediastinoscopy, 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

• rgans at risk
• rgans at risk
• Allows dose escalation

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

Currently Currently – in 2008 in 2008 Currently Currently in 2008… in 2008…

The Tools: Di i CT di ti Diagnosis = CT, mediastinoscopy, 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)

Cone Beam CT image Cone Beam CT image On treatment unit just before RT On treatment unit, just before RT

Current Efforts at Improving Cure Rate Current Efforts at Improving Cure Rate Current Efforts at Improving Cure Rate Current Efforts at Improving Cure Rate

• SBRT for early stage lung ca

SBRT for early stage lung ca

• RT dose escalation/margin reduction

Adaptive RT planning

• Adaptive RT planning
• Combination of RT with novel agents

Stereotactic RT for early stage NSCLC in Stereotactic RT for early stage NSCLC in pts who are not surgical candidates pts who are not surgical candidates pts who are not surgical candidates pts who are not surgical candidates SBRT doses = 60 G /3 f 60 Gy /3 fr 48 Gy/ 4 fr

Lung SBRT Program Lung SBRT Program at PMH at PMH at PMH at PMH

• Lung SBRT program developed fall 2004

Lung SBRT program developed fall 2004

• Current SBRT protocols:

SBRT for T1T2 peripheral tumors in inoperable pts – SBRT for T1T2 peripheral tumors in inoperable pts – SBRT for lung metastases RTOG phase II study for operable pts with – RTOG phase II study for operable pts with peripheral tumors Phase I/II dose escalation study for central tumors – Phase I/II dose escalation study for central tumors to open soon

Current Efforts at Improving Cure Rate Current Efforts at Improving Cure Rate Current Efforts at Improving Cure Rate Current Efforts at Improving Cure Rate

• RT dose escalation for N2

RT dose escalation for N2

– RTOG 0617 phase III study of 60 Gy/30 fr vs 74 Gy/37 fr with concurrent CarboPaclitaxel +/- y Cetuximab – 2 x 2 study design y g

RTOG/Intergroup 0617 study RTOG/Intergroup 0617 study RTOG/Intergroup 0617 study RTOG/Intergroup 0617 study

Current Efforts at Improving Cure Rate Current Efforts at Improving Cure Rate Current Efforts at Improving Cure Rate Current Efforts at Improving Cure Rate

• RT dose escalation for N2

RT dose escalation for N2

– RTOG 0617 phase III study of 60 Gy/30 fr vs 74 Gy/37 fr (w CarboPaclitaxel) +/- Cetuximab y ( )

• New combinations of drugs w RT

– Phase II study of Pemetrexed Platinum RT – Phase II study of Pemetrexed Platinum RT

• Role of PET scan in staging and planning

Ph III t d f PET PET (PETSTART) – Phase III study of PET vs no PET (PETSTART)

Conclusion Conclusion Conclusion Conclusion

• Progress has been made
• Higher RT doses improve local control and

survival

• Individual pts have better outcomes now

than 20 yrs ago

• Population-level statistics will not reflect

improvements until earlier diagnosis and t k i iti ti f t t t i prompt work-up initiation of treatment is universally instituted

Lung Cancer : Lung Cancer : Lung Cancer : Lung Cancer : Improving the Cure Rate Improving the Cure Rate ith R di ti ith R di ti with Radiation with Radiation

Andrea Bezjak Andrea Bezjak, MD, MSc, FRCPC The Addie MacNaughton Chair in Thoracic Radiation Oncology