Updated Analysis of SWOG-Directed Intergroup Study 0116: A Phase III Trial of Adjuvant Radiochemotherapy Versus Observation After Curative Gastric Cancer Resection
Updated Analysis of SWOG-Directed Intergroup Study 0116: A Phase III Trial of Adjuvant Radiochemotherapy Versus Observation After Curative Gastric Cancer Resection
复制标题
DOI：
10.1200/jco.2011.36.7136
复制
发表时间：
2012-07-01
影响因子：
45.3
通讯作者：
Macdonald, John S.
中科院分区：
文献类型：
--
作者：
Smalley, Stephen R.;Benedetti, Jacqueline K.;Macdonald, John S.
目的尽管多项随机试验使用术后化疗或更积极的外科手术，但胃癌手术切除的生存率仍不理想。我们对手术后局部区域失败 (LRF) 中度风险的患者进行了术后放化疗的随机 III 期试验。我们最初报告了 4 年中位随访结果。本次更新中位随访时间超过 10 年，提供了有关失败模式和继发恶性肿瘤的数据，并探讨了选定的子集分析。 患者和方法 总共，559 名原发灶 >= T3 和/或淋巴结阳性胃癌患者在 R0 切除后被随机分配接受观察组与放化疗组。在放疗之前、期间和之后给予氟尿嘧啶和亚叶酸。对所有 LRF 部位进行放射治疗，剂量为 45 Gy。结果总生存期 (OS) 和无复发生存期 (RFS) 数据表明术后放化疗持续带来巨大益处。 OS 的风险比 (HR) 为 1.32（95% CI，1.10 至 1.60；P = .0046）。 RFS 的 HR 为 1.51（95% CI，1.25 至 1.83；P < .001）。辅助放化疗显着减少了总体复发和局部复发。接受放疗的患者中有 21 名出现第二恶性肿瘤，而接受观察的患者有 8 名出现第二恶性肿瘤 (P = .21)。子集分析显示，大多数子集都具有强大的治疗益处，但具有弥漫性组织学的患者除外，这些患者表现出最小的非显着治疗效果。 结论 Intergroup 0116 (INT-0116) 表明辅助放化疗具有强大的持续益处。考虑到 RFS 和 OS 改善的幅度，包括第二恶性肿瘤在内的毒性似乎是可以接受的。 LRF 的减少可能占总体复发减少的大部分。辅助放化疗仍然是治疗原发 T3 或更大淋巴结和/或阳性淋巴结的根治性切除胃癌的合理标准疗法。
PurposeSurgical resection of gastric cancer has produced suboptimal survival despite multiple randomized trials that used postoperative chemotherapy or more aggressive surgical procedures. We performed a randomized phase III trial of postoperative radiochemotherapy in those at moderate risk of locoregional failure (LRF) following surgery. We originally reported results with 4-year median follow-up. This update, with a more than 10-year median follow-up, presents data on failure patterns and second malignancies and explores selected subset analyses.Patients and MethodsIn all, 559 patients with primaries >= T3 and/or node-positive gastric cancer were randomly assigned to observation versus radiochemotherapy after R0 resection. Fluorouracil and leucovorin were administered before, during, and after radiotherapy. Radiotherapy was given to all LRF sites to a dose of 45 Gy.ResultsOverall survival (OS) and relapse-free survival (RFS) data demonstrate continued strong benefit from postoperative radiochemotherapy. The hazard ratio (HR) for OS is 1.32 (95% CI, 1.10 to 1.60; P = .0046). The HR for RFS is 1.51 (95% CI, 1.25 to 1.83; P < .001). Adjuvant radiochemotherapy produced substantial reduction in both overall relapse and locoregional relapse. Second malignancies were observed in 21 patients with radiotherapy versus eight with observation (P = .21). Subset analyses show robust treatment benefit in most subsets, with the exception of patients with diffuse histology who exhibited minimal nonsignificant treatment effect.ConclusionIntergroup 0116 (INT-0116) demonstrates strong persistent benefit from adjuvant radiochemotherapy. Toxicities, including second malignancies, appear acceptable, given the magnitude of RFS and OS improvement. LRF reduction may account for the majority of overall relapse reduction. Adjuvant radiochemotherapy remains a rational standard therapy for curatively resected gastric cancer with primaries T3 or greater and/or positive nodes.