Impact of upfront randomization for postoperative treatment on quality of surgery in the CRITICS gastric cancer trial

Y H M Claassen,C J H Van De Velde,A K Trip,M Verheij,H Putter,H H Hartgrink,E P M Jansen,J L Dikken,N C T Van Grieken,J W Van Sandick,A Cats,M I Van Berge Henegouwen,J P B M Braak,W O De Steur,W M Meershoek-Klein Kranenbarg

doi:10.1007/s10120-018-0875-1

Y H M Claassen, C J H Van De Velde + Show 13 more

Open Access

https://doi.org/10.1007/s10120-018-0875-1

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Abstract

BackgroundPreoperative randomization for postoperative treatment might affect quality of surgery. In the CRITICS trial (ChemoRadiotherapy after Induction chemotherapy In Cancer of the Stomach), patients were randomized before treatment to receive chemotherapy prior to a D1 + gastrectomy (removal of lymph node station (LNS) 1–9 + 11), followed by either chemotherapy (CT) or chemoradiotherapy (CRT). In this analysis, the influence of upfront randomization on the quality of surgery was evaluated.MethodsQuality of surgery was analyzed in both study arms using surgicopathological compliance (removal of ≥ 15 lymph nodes), surgical compliance (removal of the indicated LNS), and surgical contamination (removal of LNS that should be left in situ). Furthermore, the ‘Maruyama Index of Unresected disease’ (MI) was evaluated in both study arms, and validated with overall survival.ResultsBetween 2007 and 2015, 788 patients with gastric cancer were included in the CRITICS study of which 636 patients were operated with curative intent. No difference was observed between the CT and CRT group regarding surgicopathological compliance (74.8% vs 70.9%, P = 0.324), surgical compliance (43.2% vs 39.2%, P = 0.381), and surgical contamination (59.4% vs 59.9%, P = 0.567). Median MI was 1 in both groups (range CT 0–88 and CRT 0–136, P = 0.700). A MI below 5 was associated with better overall survival (CT: P = 0.009 and CRT: P = 0.013).ConclusionSurgical quality parameters were similar in both study arms in the CRITICS gastric cancer trial, indicating that upfront randomization for postoperative treatment had no impact on the quality of surgery. A Maruyama Index below five was associated with better overall survival.

Highlights

Timing of randomization in multimodality trials is often a point of debate
In the CRITICS trial, gastric cancer patients were randomized before start of the treatment between adjuvant chemotherapy (CT) and adjuvant chemoradiotherapy (CRT) after preoperative chemotherapy and surgery
No significant differences were observed between the CT and the CRT group with regard to a number of surgical quality parameters

Summary

Introduction

Timing of randomization in multimodality trials is often a point of debate. This is illustrated by the criticism on the timing of randomization in the Intergroup 0116 trial where randomization for adjuvant chemoradiotherapy versus no adjuvant treatment was done after surgery [1]. As the results of the Intergroup 0116 trial and the MAGIC trial were not directly comparable due to differences in study design and eligibility criteria, the CRITICS trial (ChemoRadiotherapy after Induction chemotherapy In Cancer of the Stomach) was initiated In this multicenter trial, patients with resectable gastric cancer were treated with three cycles of preoperative chemotherapy and surgery with an adequate lymph node dissection, followed by either three cycles of chemotherapy (CT) or concurrent chemoradiotherapy (CRT). In the CRITICS trial (ChemoRadiotherapy after Induction chemotherapy In Cancer of the Stomach), patients were randomized before treatment to receive chemotherapy prior to a D1 + gastrectomy (removal of lymph node station (LNS) 1–9 + 11), followed by either chemotherapy (CT) or chemoradiotherapy (CRT) In this analysis, the influence of upfront randomization on the quality of surgery was evaluated. A Maruyama Index below five was associated with better overall survival

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