术前程序性细胞死亡蛋白-1抑制剂联合化疗用于免疫治疗敏感型局部进展期胃癌或食管胃结合部腺癌患者的近期疗效和安全性分析  

Analysis of the efficacy and safety of preoperative programmed death protein-1 inhibitor combined with chemotherapy in immunotherapy-sensitive patients with locally advanced gastric cancer or adenocarcinoma of the esophagogastric junction

作　　者：李英杰[1] 袁鹏[2] 翟建宁 姚云峰[1] 谭禄馨 李忠武[3] 张晓燕[4] 武爱文[1] Li Yingjie;Yuan Peng;Zhai Jianning;Yao Yunfeng;Tan Luxin;Li Zhongwu;Zhang Xiaoyan;Wu Aiwen(Gastrointestinal Cancer Center,Unit III,State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers,Beijing Key Laboratory of Carcinogenesis and Translational Research,Peking University Cancer Hospital&Institute,Beijing 100142,China;Department of Endoscopy,State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers,Beijing Key Laboratory of Carcinogenesis and Translational Research,Peking University Cancer Hospital&Institute,Beijing 100142,China;Department of Pathology,State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers,Beijing Key Laboratory of Carcinogenesis and Translational Research,Peking University Cancer Hospital&Institute,Beijing 100142,China;Department of Radiology,State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers,Beijing Key Laboratory of Carcinogenesis and Translational Research,Peking University Cancer Hospital&Institute,Beijing 100142,China)

机构地区：[1]北京大学肿瘤医院暨北京市肿瘤防治研究所胃肠肿瘤中心三病区,消化系肿瘤整合防治全国重点实验室,恶性肿瘤转化研究北京市重点实验室,北京100142 [2]北京大学肿瘤医院暨北京市肿瘤防治研究所内镜中心,消化系肿瘤整合防治全国重点实验室,恶性肿瘤转化研究北京市重点实验室,北京100142 [3]北京大学肿瘤医院暨北京市肿瘤防治研究所病理科,恶性肿瘤发病机制及转化研究教育部重点实验室,北京100142 [4]北京大学肿瘤医院暨北京市肿瘤防治研究所医学影像科,消化系肿瘤整合防治全国重点实验室,恶性肿瘤转化研究北京市重点实验室,北京100142

出　　处：《中华胃肠外科杂志》2024年第7期684-693,共10页Chinese Journal of Gastrointestinal Surgery

基　　金：北京市医管中心临床医学发展专项“扬帆”计划重点培育项目(ZYLX202116);北京大学肿瘤医院科学研究基金项目(PY202327)。

摘　　要：目的:评估术前程序性细胞死亡蛋白-1(PD-1)抑制剂联合CapeOx(奥沙利铂+卡培他滨)或SOX(奥沙利铂+替吉奥)化疗方案治疗免疫治疗敏感型局部进展期胃癌(LAGC)或食管胃结合部腺癌(AEG)的近期疗效和安全性。方法:采用描述性病例系列研究方法,回顾性纳入2021年8月1日至2024年1月31日期间,在北京大学肿瘤医院胃肠肿瘤中心三病区治疗前经内镜活检证实为免疫治疗敏感的LAGC或AEG患者,包括PD-L1综合阳性评分(CPS)≥5、微卫星高度不稳定(MSI-H)/错配修复缺陷(dMMR)和Epstein-Barr病毒编码RNA(EBER)阳性3种类型患者,术前均给予PD-1抑制剂联合CapeOx或SOX作为新辅助或转化治疗策略。排除免疫系统疾病、发生远处转移及人表皮生长因子受体-2阳性患者。主要观察指标为病理完全缓解、临床完全缓解、主要病理缓解、R 0切除率、手术转化率以及治疗安全性[包括免疫相关不良事件(irAE)和手术并发症情况]。 结果:共纳入39例患者,男28例,女11例;中位年龄62(44~79)岁。全组患者中,14例最初被认为不可切除者经治疗后均转化为可根治性切除(手术转化率:14/14);其余25例患者中23例行根治性手术切除,另外2例达到临床完全缓解并接受“去手术策略”,选择等待观察。全组37例(94.9%)患者接受了根治性切除术,R 0切除率为100%(37/37),病理完全缓解率为48.6%(18/37),主要病理缓解率为62.2%(23/37)。24例CPS≥5(非MSI-H/dMMR和非EBER阳性)患者中,有11例达到病理完全缓解;1例CPS=95的患者达到临床完全缓解。8例MSI-H/dMMR患者中,6例达到病理完全缓解,1例临床完全缓解。7例EBER阳性患者中,有1例达到病理完全缓解。13例患者术前活检标本与术后手术标本(不包括主要病理缓解患者)CPS评分差异有统计学意义[(7.769±5.570)比(15.538±16.870), t=2.287, P=0.041]。全组39例患者术前免疫治疗耐受良好,9例(23.1%)出现Ⅰ~Ⅱ级irAE,未发生Ⅲ~Ⅳ级irAEObjective To evaluate the short-term efficacy and safety of a preoperative combination of programmed cell death protein-1(PD-1)inhibitor with either oxaliplatin+capecitabine(CapeOx)or oxaliplatin+tegafur gimeracil oteracil potassium(SOX)in the treatment of locally advanced immunotherapy-sensitive gastric cancer(LAGC)or adenocarcinoma of the esophagogastric junction(AEG).Methods The cohort of this retrospective descriptive case series comprised patients with LAGC or AEG whose cancers had been determined to be immunotherapy-sensitive by endoscopic biopsy before treatment in the Gastrointestinal Cancer Center,Unit III,Peking University Cancer Hospital and Institute from 1 August 12021 to 31 January 2024.Patients with any one of the following three characteristics were immunotherapy-sensitive:(i)PD-L1 combined positive score(CPS)≥5;(ii)microsatellite instability-high(MSI-H)/mismatch repair deficiency(dMMR);or(iii)Epstein-Barr virus-encoded RNA(EBER)positivity.All study patients received PD-1 inhibitors combined with CapeOx or SOX as a neoadjuvant or conversion treatment strategy before surgery.Patients with immune system diseases,distant metastases,or human epidermal growth factor receptor 2 positivity were excluded.Factors analyzed included pathological complete response,clinical complete response,major pathological response,R0 resection rate,surgical conversion rate,and safety of the treatment,including immune-related adverse events(irAEs)and surgical complications.Results The study cohort comprised 39 patients(28 men and 11 women)of median age 62(range 44–79)years.After the above-described preoperative treatment,radical resection of the 14 tumors that were initially considered unresectable was achieved(surgical conversion rate:14/14).Twenty-three of the remaining 25 patients underwent radical resection.The last two patients achieved clinical complete responses and opted for a"non-surgical strategy"(watch and wait).Overall,37 patients(94.9%)underwent radical resection,with an R0 resection rate of 100%(37/37),pa

关 键 词：胃肿瘤 局部进展期 食管胃结合部肿瘤 程序性细胞死亡蛋白-1抑制剂 新辅助治疗 转化治疗 病理完全缓解率 临床完全缓解率 

分 类 号：R735.2[医药卫生—肿瘤]