Optimal Therapy Sequence for Stage II-III Proximal Gastric Adenocarcinoma: Chemoradiation and Surgery
This study explores the optimal sequence of therapies for patients with Stage II-III adenocarcinoma of the proximal stomach, specifically focusing on chemoradiation followed by surgery. The findings from various trials, including INT.0116 and SCOPE1, highlight the significant survival benefits of postoperative chemoradiation compared to surgery alone. The analysis reveals local failure rates and acute toxicities associated with treatment, emphasizing the importance of multimodal approaches in managing this challenging cancer type. Preoperative chemotherapy also shows promise in improving outcomes.
Optimal Therapy Sequence for Stage II-III Proximal Gastric Adenocarcinoma: Chemoradiation and Surgery
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Presentation Transcript
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 CMTSURGERY 3-Year Survival (%) 40 30** Local Failure (%) 19 29
INT 0116 – 10.3 Yr Median F/U Smalley et al JCO 2012
Acute Toxicity – INT 0116 % Toxicity 33 Gr 3-4 Diarrhea 54 Gr 3-4 Neutropenia 1 Death • 65% Completed all therapy • 17% Stopped for toxicity
Postop S1 (ACTS-GC) · 1059 pts, Stage II/III · D2 resection S1 Wks 1-4, q 6 weeks x 1 yr · Gr 3+ toxicity < 5% % 5-Yr % LR SurvivalFailureHR Surgery only 61 8 0.669 Postop S1 72 13 0.572 Sasaco et al JCO 2011
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 RT Zhang IJROBP 1998 370 pts, clinically resectable disease % 5-Yr % Failure %R0 SurvivalLocalLN Surgery 62 20 47 55 40 Gy 80* 30* 33 31
Phase III Preop CT +/- CMT for GE Junction Adeno · 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 Stahl et al JCO 2009
Phase III Preop CT +/- CMT for GE Junction Adeno Induction Induction ChemotherapyChemoRTP # Entered 49 45 % R0 Resection 70 72 - % Mortality 4 10 - % pCR 2 16 0.03 3-Yr Survival 28 47 0.07 % 3-Yr Local Fail 41 24 0.06
Preop CMT for Gastric RTOG 9904 • 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 JCO 2006
CROSS Study Group Surgery ∙ 368 pts ∙ 75% Adeno ∙ T1N1 or ∙ T2-3N0-1 Preop paclitaxel/carboplat Concurrent 41.4 Gy (1.8 Gy/d) ∙ pCR: 29% (adeno: 23% vs. 49% SCC), 4% mortality R0% 5-Yr S Preop` 92 59 Surg 69 48 p<0.003 p=0.001 Van Hagen NEJM 2012
CROSS I + II Trials 422 Pts, 374 underwent surgery 75% adeno F/U: 45 M median, 24 M min #%LR%PS%DF Preop 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 50Gy/CDDP/Cape 50 Gy/CDDP/Cape + Cetuximab ∙ 258 Pts, Stage I-III ∙ (97% stage II,III) ∙ 25% Adeno ∙ Stopped early – met futility % 2-Yr Median % Gr 3+ CetuximabSurvivalSurvivalNon-heme Toxicity Yes 41 22 m 79 No 56 25 m 63
Conclusions • Postop CMT increases survival • Overlap between GE junction and gastric • Preop CMT improves survival (CROSS) • Preop RT fields are smaller (no postop bed)
