pMMR局部进展期中低位直肠癌行新辅助放化疗联合替雷利珠单克隆抗体的探索研究  

Exploration of neoadjuvant chemoradiotherapy combined with tislelizumab for proficient mismatch repair locally advanced mid-low rectal cancer

作　　者：高加勒 张潇 杨正阳 庞凯 吴国聪[1] 邓薇[1] 白志刚[1] 张洁[1] 徐瑞[1] 陈光勇[1] 李文竹[1] 张宏[1] 姚宏伟[1] 张忠涛[1] GAO Jia-le;ZHANG Xiao;YANG Zheng-yang(Department of General Surgery,Bejing Friendship Hospital,Capital Medical University,&National Clinical Research Center for Digestive Diseases,Bejing 100050,China;不详)

机构地区：[1]首都医科大学附属北京友谊医院普通外科国家消化系统疾病临床医学研究中心,北京100050

出　　处：《中国实用外科杂志》2022年第8期913-919,共7页Chinese Journal of Practical Surgery

基　　金：国家重点研发计划资助(No.2017YFC0110904);北京市临床重点专科基金卓越项目(No.2018-118);首都卫生发展科研重点项目(No.2018-1-1111);首都医科大学结直肠肿瘤临床诊疗与研究中心基金(No.1192070313);首都医科大学附属北京友谊医院科研启动基金(No.YYQDKT2016-5)。

摘　　要：目的 探索长程放化疗联合替雷利珠单克隆抗体作为错配修复基因蛋白无缺失型(pMMR)局部进展期中低位直肠癌病人新辅助治疗方案的安全性和有效性。方法 前瞻性分析2021年4月至2021年12月首都医科大学附属北京友谊医院11例临床分期为cT3-4N0M0或cT1-4N+M0接受全直肠系膜切除手术且术前行新辅助放化疗联合替雷利珠单克隆抗体治疗的pMMR中低位直肠癌病人临床资料。研究主要终点为病理完全缓解,同时分析药物不良反应发生率,手术安全性,术后并发症发生率以及病理组织学改变。结果 11例病人均完成放化疗,10例病人接受3次替雷利珠单克隆抗体治疗,1例接受2次替雷利珠单克隆抗体治疗。1例(9.1%)病人出现3级免疫性肠炎的不良反应。保肛手术率为100.0%。1例病人术后出现Clavien-DindoⅡ级吻合口漏。所有病人肿瘤均为pMMR,共有6例(54.5%)病人达到病理完全缓解,3例(27.3%)达到主要病理缓解,客观缓解率达100.0%。6例病理完全缓解的病人中,有2例(18.2%)达到临床完全缓解。结论 pMMR局部进展期中低位直肠癌病人行长程放化疗联合靶向程序性细胞死亡受体-1(PD-1)抗体治疗具有良好的安全性和有效性,并不增加手术的并发症发生率,后续需要更大样本的研究进行进一步的验证。ObjectiveTo explore the safety and efficacy of long-course chemoradiotherapy combined with tislelizumab as neoadjuvant therapy for patients with proficient mismatch repair(pMMR)locally advanced mid-low rectal cancer.MethodsThe clinical data of pMMR locally advanced mid-low rectal cancer patients with clinical stage cT3-4N0M0or cT1-4N+M0 who underwent total mesorectal resection followed by neoadjuvant chemoradiotherapy combined with tislelizumab enrolled at Beijing Friendship Hospital affiliated to Capital Medical University from April 2021 to December2021 were prospectively analyzed. The primary endpoint of the study was pathological complete response, and theincidence of adverse drug reactions, surgical safety,postoperative complication rate, and histopathologicalchanges were analyzed.ResultsAll the patientscompleted chemoradiotherapy, 10 patients received 3 cycles of tislelizumab, and 1 patient received 2 cycles. One patient had the Grade 3 adverse reactionof immune-related colitis(9.1%). Sphincter-preserving surgery was performed in all patients(100%). One patient developed Clavien-Dindo IIanastomotic leakage after surgery. All the patients hadp MMR tumors. A total of 6 patients achieved pathological complete response(54.5%), and 3 patients achieved majorpathological response(27.3%), with an objective response rate of 100.0%. Among the 6 patients with pathologicalcomplete response, 2 patients achieved clinical complete response(18.2%).ConclusionChemoradiotherapy combinedwith PD-1 antibody therapy in patients with p MMR locally advanced mid-low rectal cancer has good safety andeffectiveness, and does not increase the complication rate of surgery. Follow-up studies with larger samples are needed tobe further verified.

关 键 词：直肠癌 新辅助治疗 免疫检查点抑制剂 

分 类 号：R6[医药卫生—外科学]