Department of Surgical Oncology, Leiden University Medical Center, Leiden, the Netherlands.
Department of Radiation Oncology, the Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands.
Ann Oncol. 2021 Mar;32(3):360-367. doi: 10.1016/j.annonc.2020.11.004. Epub 2020 Nov 20.
The Intergroup 0116 and the MAGIC trials changed clinical practice for resectable gastric cancer in the Western world. In these trials, overall survival improved with post-operative chemoradiotherapy (CRT) and perioperative chemotherapy (CT). Intention-to-treat analysis in the CRITICS trial of post-operative CT or post-operative CRT did not show a survival difference. The current study reports on the per-protocol (PP) analysis of the CRITICS trial.
The CRITICS trial was a randomized, controlled trial in which 788 patients with stage Ib-Iva resectable gastric or esophagogastric adenocarcinoma were included. Before start of preoperative CT, patients from the Netherlands, Sweden and Denmark were randomly assigned to receive post-operative CT or CRT. For the current analysis, only patients who started their allocated post-operative treatment were included. Since it is uncertain that the two treatment arms are balanced in such PP analysis, adjusted proportional hazards regression analysis and inverse probability weighted analysis were used to minimize the risk of selection bias and to estimate and compare overall and event-free survival.
Of the 788 patients, 478 started post-operative treatment according to protocol, 233 (59%) patients in the CT group and 245 (62%) patients in the CRT group. Patient and tumor characteristics between the groups before start of the post-operative treatment were not different. After a median follow-up of 6.7 years since the start of post-operative treatment, the 5-year overall survival was 57.9% (95% confidence interval: 51.4% to 64.3%) in the CT group versus 45.5% (95% confidence interval: 39.2% to 51.8%) in the CRT group (adjusted hazard ratio CRT versus CT: 1.62 (1.24-2.12), P = 0.0004). Inverse probability weighted analysis resulted in similar hazard ratios.
After adjustment for all known confounding factors, the PP analysis of patients who started the allocated post-operative treatment in the CRITICS trial showed that the CT group had a significantly better 5-year overall survival than the CRT group (NCT00407186).
Intergroup 0116 和 MAGIC 试验改变了西方世界可切除胃癌的临床实践。在这些试验中，术后放化疗（CRT）和围手术期化疗（CT）改善了总生存率。CRITICS 试验的意向治疗分析显示，术后 CT 或术后 CRT 之间没有生存差异。本研究报告了 CRITICS 试验的方案分析结果。
CRITICS 试验是一项随机对照试验，纳入了 788 例可切除胃或食管胃腺癌的 Ib-Iva 期患者。在开始术前 CT 之前，来自荷兰、瑞典和丹麦的患者被随机分配接受术后 CT 或 CRT。对于本次分析，仅纳入开始接受分配的术后治疗的患者。由于在这种方案分析中，两个治疗臂的平衡情况不确定，因此使用调整后的比例风险回归分析和逆概率加权分析来最小化选择偏倚的风险，并估计和比较总生存率和无事件生存率。
在 788 例患者中，有 478 例根据方案开始了术后治疗，CT 组 233 例（59%），CRT 组 245 例（62%）。在开始术后治疗前，两组患者和肿瘤特征无差异。在开始术后治疗后中位随访 6.7 年后，CT 组的 5 年总生存率为 57.9%（95%置信区间：51.4%至 64.3%），而 CRT 组为 45.5%（95%置信区间：39.2%至 51.8%）（CRT 与 CT 的调整风险比：1.62（1.24-2.12），P=0.0004）。逆概率加权分析得出了相似的风险比。
在调整了所有已知的混杂因素后，CRITICS 试验中开始接受分配的术后治疗的患者的方案分析显示，CT 组的 5 年总生存率显著优于 CRT 组（NCT00407186）。
