Post on 06-Feb-2016
description
What is the optimal sequence of therapies for stage II-III
adenocarcinoma of the proximal stomach? -
Chemoradiation followed by surgery
Bruce Minsky
INT 0116 Adjuvant Gastric Trial
• T3 and/or N1-2 (85%)• 20% GEJ• 54% D0
5-FU/LV x 4 + 45 Gy
Surgery alone
CMT SURGERY3-Year Survival (%) 40 30**Local Failure (%) 19 29
INT 0116 – 10.3 Yr Median F/U
Smalley et al JCO 2012
Postop RT Fields
Acute Toxicity – INT 0116
% Toxicity33 Gr 3-4 Diarrhea54 Gr 3-4 Neutropenia1 Death
• 65% Completed all therapy• 17% Stopped for toxicity
Postop S1 (ACTS-GC)
Sasaco et al JCO 2011
· 1059 pts, Stage II/III· D2 resection S1 Wks 1-4, q 6 weeks x 1 yr· Gr 3+ toxicity < 5%
% 5-Yr % LRSurvival Failure HR
Surgery only 61 8 0.669
Postop S1 72 13 0.572
Upper GI Adenocarcinomas
• Overlap of GE Junction and Gastric (Siewert II and III)
• 20% GE junction in INT 0116
• Preop CMT for GE junction
Adjuvant Preop RTZhang IJROBP 1998
370 pts, clinically resectable disease
% 5-Yr % Failure%R0 Survival Local LN
Surgery 62 20 47 55
40 Gy 80* 30* 33 31
Phase III Preop CT +/- CMT for GE Junction Adeno
Stahl et al JCO 2009
· 119/126 eligible pts T3-4Nx GE junction (Siewert I-III)
FU/LV/CDDP X 2.5
FU/LV/CDDP VP-16/CDDP X 2.5 30 Gy (2 Gy/d)
Surgery
Surgery
Phase III Preop CT +/- CMT for GE Junction Adeno
Induction Induction Chemotherapy ChemoRT P
# Entered 49 45% R0 Resection 70 72 -% Mortality 4 10 -% pCR 2 16 0.033-Yr Survival 28 47 0.07% 3-Yr Local Fail 41 24 0.06
Preop CMT for Gastric
• 43 pts • EUS T2-3 and/or N1-2, lap negative• 5FU/LV/CDDP x 2 then 45 Gy/5FU/Paclitaxel• 36 had surgery (7 POD), 50% D2• 26% pCR• 21% Gr 4 toxicity• 23 M median survival
RTOG 9904
JCO 2006
CROSS Study Group
Van Hagen NEJM 2012
∙ 368 pts∙ 75% Adeno∙ T1N1 or∙ T2-3N0-1
Surgery
Preop paclitaxel/carboplatConcurrent 41.4 Gy (1.8 Gy/d)
∙ pCR: 29% (adeno: 23% vs. 49% SCC), 4% mortality
R0 % 5-Yr SPreop` 92 59Surg 69 48
p<0.003p=0.001
CROSS I + II Trials
422 Pts, 374 underwent surgery75% adenoF/U: 45 M median, 24 M min
# %LR %PS %DFPreop 34 14 35
p<0.001 p<0.001 p=0.025
Surg 14 4 29
5% LR (1% isolated) in the RT field
Oppedijk et al, JCO 2014
SCOPE1: CMT+ Cetuximab
∙ 258 Pts, Stage I-III ∙ (97% stage II,III)∙ 25% Adeno
50Gy/CDDP/Cape
50 Gy/CDDP/Cape + Cetuximab
∙ Stopped early – met futility
% 2-Yr Median % Gr 3+Cetuximab Survival Survival Non-heme ToxicityYes 41 22 m 79
No 56 25 m 63
RTOG 1010
Conclusions
• Postop CMT increases survival
• Overlap between GE junction and gastric
• Preop CMT improves survival (CROSS)
• Preop RT fields are smaller (no postop bed)