中国实用外科杂志

中国实用外科杂志

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晚期胃癌免疫检查点抑制剂联合手术治疗临床疗效分析：一项多中心回顾性研究v

王恒越1，陈    杰2，王书昌3，罗天航4，黄    陈5，张子臻3，郑    瑞4，方    圆5，马君俊1，张鲁阳1，李树春1，林中俊1，赵恩昊3，刘凤林2，臧    潞1   

  1. 1上海交通大学医学院附属瑞金医院普通外科，上海市微创外科临床医学中心，上海200025；2复旦大学附属肿瘤医院胃外二科，上海 200032；3上海交通大学医学院附属仁济医院胃肠外科，上海200127；4海军军医大学附属长海医院胃肠外科，上海200433；5上海交通大学医学院附属第一人民医院胃肠外科，上海200080
  • 出版日期:2025-04-01

  • Online:2025-04-01

摘要： 目的    探讨应用免疫检查点抑制剂联合手术治疗胃癌或食管胃结合部腺癌(AEG)的疗效及安全性。
方法    回顾性分析2021年5月至2023年8月上海市5家大型三甲医院收治的112例应用免疫检查点抑制剂+化疗联合或不联合靶向治疗进行转化治疗的胃癌或AEG手术病人的临床资料，其中cⅣA期43例，cⅣB期69例。免疫治疗药物均为程序性死亡受体1抑制剂，化疗方案主要为SOX方案（奥沙利铂+替吉奥）、XELOX方案（奥沙利铂+卡培他滨）等，靶向治疗药物包括曲妥珠单抗和阿帕替尼。观察指标有治疗相关不良反应、手术情况及相关并发症、转化治疗后的疗效评价以及预后生存情况。结果    112例病人治疗相关不良反应主要为骨髓抑制、疲乏等，其中Ⅲ级及以上治疗相关不良反应占30.4%（34/112）；免疫相关不良反应主要为皮疹和甲状腺功能减退症，发生率为19.6%（22/112）。术前治疗周期为4（4，6）个。R0手术切除率为82.1%（92/112）。手术相关并发症发生率为14.3%（16/112），主要为吻合口漏、乳糜漏等，其中Clavien-Dindo分级Ⅰ～Ⅱ级并发症13例（11.6%），Ⅲ级并发症3例（2.7%），无Ⅳ级及以上并发症。客观缓解率为79.5%（89/112），病理完全缓解率为20.5%（22/112），主要病理缓解率为44.6%（50/112）。中位随访时间为22.6（95%CI 19.8-25.4）个月，中位总生存期为37.3（95%CI 20.6-54.0）个月，中位无进展生存期为22.5（95%CI 15.8-29.2）个月。1年、2年总生存率分别为86.6%、65.0%，1年、2年无进展生存率分别为73.2%、44.9%。结论    接受免疫检查点抑制剂联合手术治疗的晚期胃癌或AEG病人预后良好，且治疗相关不良反应及手术并发症的发生率均处于可接受范围。

关键词: 胃癌, 食管胃结合部腺癌, 免疫检查点抑制剂, 手术治疗

Abstract: To explore the efficacy and safety of applying immune checkpoint inhibitors combined with surgery in patients with stage Ⅳ gastric cancer or esophagogastric junction adenocarcinoma. Methods    The clinical data of 112 patients with gastric cancer or esophagogastric junction adenocarcinoma who were treated with immune checkpoint inhibitors before surgery at 5 centers in Shanghai between May 2021 and August 2023 were retrospectively analyzed. The study cohort comprised 43 patients with stage cⅣA and 69 patients with stage cⅣB. All patients received immune checkpoint inhibitors targeting the programmed cell death-1. Chemotherapy regimens mainly included SOX, XELOX regimen,  etc. Targeted therapeutic drugs include trastuzumab and apatinib. Observation indicators include treatment-related adverse events, operation conditions and operation-related complications, the short-term efficacy, and the prognosis. Results    In the whole group of 112 patients, the main treatment-related adverse events were bone marrow suppression and fatigue, among which grade Ⅲ and above adverse events accounted for 30.4% (34/112), and the main immune-related adverse events were rash and hypothyroidism with an incidence of immune-related adverse events was 19.6% (22/112). The median treatment period before surgery was 4 (4,6) , and the R0 resection rate reached 82.1% (92/112). The incidence of surgery-related complications was 14.3% (16/112), mainly including anastomotic leakage and chylous leakage. There were 13 cases with grade Ⅰ to Ⅱ complications (11.6%), 3 cases with grade Ⅲ complications (2.7%), and no case with grade Ⅳ or above complications. In the whole group, ORR was 79.5% (89/112), pCR rate was 20.5% (22/112), and MPR  rate was 44.6% (50/112). The median follow-up time of the whole group was 22.6 (95%CI 19.8-25.4) month, the median overall survival (OS) was 37.3 (95%CI 20.6-54.0) months, and the median progression free survival (PFS) was 22.5  (95%CI 15.8-29.2) months. The 1- and 2-year OS rates were 86.6% and 65.0%. The 1- and 2-year PFS rates were 73.2% and 44.9%. Conclusion    For patients with stage Ⅳ gastric cancer or adenocarcinoma of esophagogastric junction, preoperative application of immune checkpoint inhibitors combined with surgery has a good therapeutic effect and prognosis. The incidence of treatment-related adverse reactions and surgery-related complications are acceptable.

Key words: gastric cancer, adenocarcinoma of esophagogastric junction, immune checkpoint inhibitor, surgical treatment