Allan Price NHS Lothian, Edinburgh, UK

Transcription

1 Allan Price NHS Lothian, Edinburgh, UK Radiotherapy Dose Volume Timing Technique PCI Surgery Systemic agents 1

2 Study Dose Time Induction CT Ann Arbor Gy Duke Gy RTOG 77.4 Gy 74 Gy w 5-6 w Not stated 7 w No Yes Volume Toxicity 23% IF Acute lung 2 phase Late lung IF IF Late lung MSK 84 Gy 9 w 16% 2 phase Late lung NKI 74.3 Gy 6 w 18% IF Acute lung Study n Dose Time Chemotherapy Toxicity RTOG Gy NCCTG Gy 7.5 w Weekly CT 1/9 acute lung w Weekly CT 1/6 acute lung UNC Gy w Induction & weekly CT 24% late 2

3 RTOG 0617 Arm A 60 Gy 30 fx 6 w + concomitant weekly carboplatin /paclitaxel + 2 cycles sequential carboplatin / paclitaxel Arm B 74 Gy 37 fx 7.5 w + concomitant weekly carboplatin / paclitaxel + 2 cycles sequential carboplatin / paclitaxel Arm C 60 Gy 30 fx 6 w + concomitant weekly carboplatin / paclitaxel /cetuximab + 2 cycles sequential carboplatin / paclitaxel /cetuximab Arm D 74 Gy 37 fx 7.5 w + concomitant weekly carboplatin / paclitaxel /cetuximab + 2 cycles sequential carboplatin / paclitaxel /cetuximab 203 participants 102 centres Study CT Volume Nodal failure Ann Arbor 24% IF 6% RTOG 15% IF <10% MAASTRO 16% IF 7% NKI 18% IF 7% 3

4 Auperin, 2007 Radiotherapy v sequential chemoradiotherapy OS HR 0.88 ( ) LRP HR 1.18 ( ) DP HR 0.73 ( ) Radiotherapy v concomitant chemoradiotherapy OS HR 0.88 ( ) LRP HR 0.87 ( ) DP HR 0.95 ( ) Sequential v concomitant chemoradiotherapy OS HR 0.83 ( ) LRP HR 0.76 ( ) DP HR 1.04 ( ) EORTC guidelines Tumour motion CT scanning PET scanning Target volume generation Dose calculations Treatment delivery OAR dose constraints 4

5 Tumour motion Image-guided set-up Breath-holding Planning studies suggest lower OAR dose Not all can comply Tracking Predictive But movement and respiration irregular Gating Phantom studies suggest benefit But which target? External or internal marker? Fast CT Slow CT 4D CT 5

6 Does it make volumes more accurate? Yes Van Baardwijk 2007 PET-based auto-contouring and pathology 23 patients Correlation maximum diameter, r = 0.9 Smaller GTV with auto-contouring Less inter-observer variation with autocontouring RT in Stage III NSCLC - PET Does it make volumes more accurate? Yes Schaefer 2008 Contrast-oriented algorithm including Threshold SUV Mean SUV in RoI Background uptake Difference 8 PET- & CT-PTVs mm 6

7 Does it make volumes more accurate? No Faria patients Contoured with CT and CT-PET 18 altered PTV, 12 smaller, 6 larger Impossible to accurately distinguish cancer from non-cancer soft tissue RT in Stage III NSCLC - PET Does it make volumes more accurate? No Stroom patients Contoured using CT-PET Histopathological confirmation 4 GTV too large, mean 53% 1 GTV too small, 40% 7

8 Does it make volumes more accurate? No Sura local relapses 13 (50%) marginal relapse Visual incorporation of PET data for GTV delineation might be inadequate What is the target? Windowing? Spicules? Size-significant but PET/EBUS ve nodes? Node or station? Skip or contiguous spread? Pre- or post-chemotherapy? Expansion from GTV to CTV to PTV? OAR margins? Planning algorithms? 8

9 Hitting the target Increase complexity, increase errors IMRT Gating Breath-holding Tracking techniques OBI Pre-treatment Local control Lung V20 MLD ILD Heart We don t know Signal vs noise Spinal cord 45-48Gy Oesophagus Acute manageable Late very rare Bronchi 74 Gy 9

10 Series N at risk % brain metastases SWOG database, CMT NSCLC stage IIIA/B SAKK CT-S pn2 NSCLC German multicentre, CT-RT-S IIIA NSCLC UPenn, CTRT-S IIIA NSCLC % (20% brain only) 75 17% 51 35% 53 23% Edinburgh, CTRT IIIA/B % Series n RT dose Brain failure no RT (%) Brain failure RT (%) VALG Gy 10 fx 13 6 RTOG Gy 10 fx 19 9 Umsawasdi Gy 10 fx 27 4 SWOG Gy 15 fx 11 1 Pottgen Gy 15 fx 27 9 RTOG Gy 15 fx

11 Clear evidence of reduction in cerebral metastases Survival benefit not confirmed Trials difficult because of competing risks and competing questions Next IPD meta-analysis? 1990s Intergroup 0139 EORTC GLCCG The world has changed Staging Surgery Radiotherapy How to identify subset which benefits without compromising (majority?) who do not? 11

12 Chemotherapy Pemetrexed Docetaxel Etoposide Vinorelbine Biologicals EGFR TKI Cetuximab Vaccines Anti-MUC1 12