基于多中心真实世界数据的结直肠癌联合免疫治疗的新辅助治疗安全性及其疗效  

Multicenter real-world study on safety and efficacy of neoadjuvant therapy in combination with immunotherapy for colorectal cancer

作　　者：刘新志 熊振 肖斌毅 于冠宇 李英杰[1] 姚云峰[1] 陶凯雄[2] 丁培荣[3] 张卫 武爱文[1] Liu Xinzhi;Xiong Zhen;Xiao Yibin;Yu Guangyu;Li Yingjie;Yao Yunfeng;Tao Kaixiong;Ding Peirong;Zhang Wei;Wu Aiwen(Gastrointestinal Cancer Center,Unit III,Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education),Peking University Cancer Hospital&Institute,Beijing 100142,China;Department of Colorectal Surgery,Sun Yat-sen University Cancer Center,Guangzhou 510060,China Department of Gastrointestinal Surgery,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430022,China;Department of Colorectal Surgery,Sun Yat-sen University Cancer Center,Guangzhou 510060,China;Department of Colorectal Surgery,Changhai Hospital,Navy Medical University,Shanghai 200433,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恶性肿瘤发病机制及转化研究教育部重点实验室胃肠肿瘤中心三病区,北京100142 [2]华中科技大学同济医学院附属协和医院胃肠外科,武汉430022 [3]中山大学肿瘤防治中心结直肠外科,广州510060 [4]海军军医大学附属长海医院肛肠外科,上海200433

出　　处：《中华胃肠外科杂志》2022年第3期219-227,共9页Chinese Journal of Gastrointestinal Surgery

基　　金：国家自然科学基金(82173156);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)。

摘　　要：目的通过总结分析国内多中心、真实世界的大样本数据,为联合免疫治疗的新辅助治疗对结直肠癌患者的临床应用提供借鉴和依据。方法本研究为回顾性、多中心、病例系列研究。回顾性收集2017年1月至2021年10月期间,北京大学肿瘤医院(55例)、华中科技大学同济医学院附属协和医院(19例)、中山大学肿瘤防治中心(13例)和海军军医大学附属长海医院(7例)共计94例患者联合新辅助免疫治疗的结直肠癌患者资料,其中男性48例,女性46例;中位年龄58岁。直肠癌81例,结肠癌13例(2例为结肠双原发癌);肿瘤TNM分期:Ⅱ期12例,Ⅲ期82例;肿瘤高分化46例,中分化37例,低分化11例。26例(27.7%)为错配修复缺陷(dMMR)和微卫星高度不稳定(MSI-H),行单纯免疫治疗,主要为程序性死亡蛋白-1(PD-1);68例(72.3%)为错配修复正常(pMMR)和微卫星稳定(MSS),行免疫联合新辅助治疗,主要为CapeOx(卡培他滨+奥沙利铂)联合PD-1+长程或短程放疗,或PD-1联合细胞毒T淋巴细胞相关抗原4(CTLA-4)。按美国国立癌症研究所通用毒性标准3.0版分析评价新辅助联合免疫治疗期间的不良反应;了解手术情况并按照Clavien-Dindo分级标准评价手术并发症;联合新辅助免疫治疗的疗效评估包括以下指标:主要病理学缓解(MPR),定义为新辅助治疗诱导的肿瘤消退在病理上残留肿瘤≤10%;病理完全缓解(pCR)定义为新辅助治疗诱导的肿瘤消退患者在病理上未见残留肿瘤;肿瘤评效为疾病控制率(DCR),即完全缓解(CR)、部分缓解(PR)和疾病稳定(SD)患者在全组中所占的比例;客观缓解率(ORR),为CR+PR。结果全组94例患者接受新辅助联合免疫治疗的中位周期数为4(1~10)个,免疫相关不良反应发生率为37.2%(35/94),包括皮肤相关不良反应35例(37.2%)、甲状腺功能异常21例(22.3%)和免疫性肠炎8例(8.5%),其中Ⅲ级不良反应占1.1%。末次新辅助联合免疫治疗至手术的中位时间�Objective To provide reference and evidence for clinical application of neoadjuvant immunotherapy in patients with colorectal cancer through multicenter large-scale analysis based on real-world data in China.Methods This was a retrospective multicenter case series study.From January 2017 to October 2021,data of 94 patients with colorectal cancer who received neoadjuvant immunotherapy in Peking University Cancer Hospital(55 cases),Union Hospital of Tongji Medical College of Huazhong University of Science and Technology(19 cases),Sun Yat-sen University Cancer Center(13 cases)and Changhai Hospital of Navy Medical University(7 cases)were retrospectively collected,including 48 males and 46 females.The median age was 58 years.Eighty-one cases were rectal cancer and 13 cases were colon cancer(2 cases of double primary colon cancer).Twelve cases were TNM staging II and 82 cases were stage III.Forty-six cases were well differentiated,37 cases were moderately differentiated and 11 cases were poorly differentiated.Twenty-six patients(27.7%)with mismatch repair defects(dMMR)and microsatellite instability(MSI-H)were treated with immunotherapy alone,mainly programmed cell death protein-1(PD-1);sixty-eight cases(72.3%)with mismatch repair proficient(pMMR)and microsatellite stability(MSS)were treated with immune combined with neoadjuvant therapy,mainly CapeOx(capecitabine+oxaliplatin)combined with PD-1 antibody plus long-or short-course radiotherapy,or PD-1 antibody combined with cytotoxic T lymphocyte associated antigen 4(CTLA-4)antibody.Analysis and evaluation of adverse events during neoadjuvant immunotherapy were performed according to the National Cancer Institute Common Toxicity Standard version 3.0;the surgical complications were evaluated according to the Clavien-Dindo grading standard;the efficacy evaluation of neoadjuvant immunotherapy included the following indicators:major pathological remission(MPR)was defined as tumor regression induced by neoadjuvant therapy in pathology residual tumor≤10%;pathological complete

关 键 词：结直肠癌 新辅助治疗 免疫治疗 并发症 病理缓解 免疫检查点抑制剂 

分 类 号：R735.34[医药卫生—肿瘤]