Importance The association between quality of surgery and overall survival in patients affected by localized gastrointestinal stromal tumors (GIST) is not completely understood.

Objective To assess the risk of death with and without imatinib according to microscopic margins status (R0/R1) using data from a randomized study on adjuvant imatinib.

Design, Setting, and Participants This is a post hoc observational study on patients included in the randomized, open-label, phase III trial, performed between December 2004 and October 2008. Median follow-up was 9.1 years (IQR, 8-10 years). The study was performed at 112 hospitals in 12 countries. Inclusion criteria were diagnosis of primary GIST, with intermediate or high risk of relapse; no evidence of residual disease after surgery; older than 18 years; and no prior malignancies or concurrent severe/uncontrolled medical conditions. Data were analyzed between July 17, 2017, and March 1, 2020.

Interventions Patients were randomized after surgery to either receive imatinib (400 mg/d) for 2 years or no adjuvant treatment. Randomization was stratified by center, risk category (high vs intermediate), tumor site (gastric vs other), and quality of surgery (R0 vs R1). Tumor rupture was included in the R1 category but also analyzed separately.

Main Outcomes and Measures Primary end point of this substudy was overall survival (OS), estimated using Kaplan-Meier method and compared between R0/R1 using Cox models adjusted for treatment and stratification factors.

Results A total of 908 patients were included; 51.4% were men (465) and 48.6% were women (440), and the median age was 59 years (range, 18-89 years). One hundred sixty-two (17.8%) had an R1 resection, and 97 of 162 (59.9%) had tumor rupture. There was a significant difference in OS for patients undergoing an R1 vs R0 resection, overall (hazard ratio [HR], 2.05; 95% CI, 1.45-2.89) and by treatment arm (HR, 2.65; 95% CI, 1.37-3.75 with adjuvant imatinib and HR, 1.86; 95% CI, 1.16-2.99 without adjuvant imatinib). When tumor rupture was excluded, this difference in OS between R1 and R0 resections disappeared (HR, 1.05; 95% CI, 0.54-2.01).

Conclusions and Relevance The difference in OS by quality of surgery with or without imatinib was associated with the presence of tumor rupture. When the latter was excluded, the presence of R1 margins was not associated with worse OS.

Trial Registration ClinicalTrials.gov Identifier: NCT00103168

重要性 局限性胃肠道间质瘤（GIST）影响的患者的手术质量与总体生存之间的关系尚未完全了解。

目的 使用随机辅助研究的伊马替尼研究数据，根据微观边界状态（R0 / R1）评估有或无伊马替尼的死亡风险。

设计，背景和参与者 这是一项针对2004年12月至2008年10月之间进行的随机，开放标签，III期临床试验患者的事后观察性研究。中位随访时间为9.1年（IQR，8-10年） ）。该研究在12个国家的112家医院中进行。纳入标准为原发性GIST的诊断，具有中等或高复发风险；没有手术后残留疾病的证据；年满18岁；且无先前的恶性肿瘤或并发的严重/无法控制的医疗状况。分析了2017年7月17日至2020年3月1日之间的数据。

干预措施 术后患者被随机分配接受伊马替尼（400 mg / d）治疗2年或不接受辅助治疗。根据中心，风险类别（高危与中危），肿瘤部位（胃与其他）和手术质量（R0与R1）对随机分组。肿瘤破裂被包括在R1类别中，但也被单独分析。

主要结果和措施 该子研究的主要终点是总生存期（OS），使用Kaplan-Meier方法进行估计，并使用针对治疗和分层因素调整的Cox模型在R0 / R1之间进行比较。

结果 共纳入908例患者。男性为51.4％（465），女性为48.6％（440），中位年龄为59岁（18-89岁）。162例（17.8％）切除了R1，162例中有97例（59.9％）发生了肿瘤破裂。接受R1 vs R0切除的患者，总体（危险比[HR]，2.05； 95％CI，1.45-2.89）和治疗组（HR，2.65； 95％CI，1.37-3.75）在OS上存在显着差异含伊马替尼辅助药物和HR，1.86; 95％CI，1.16-2.99（不含伊马替尼辅助药物）。当排除肿瘤破裂时，R1和R0切除之间的OS差异消失（HR，1.05； 95％CI，0.54-2.01）。

结论和相关性 在有或没有伊马替尼的情况下，手术质量所致的OS差异与肿瘤破裂的存在有关。当排除后者时，R1余量的存在与较差的操作系统无关。

试验注册 ClinicalTrials.gov标识符：NCT00103168