中国实用外科杂志 ›› 2022, Vol. 42 ›› Issue (08): 913-919.DOI: 10.19538/j.cjps.issn1005-2208.2022.08.13

• 论著 • 上一篇    下一篇

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

高加勒,张    潇,杨正阳,庞    凯,吴国聪,邓    薇,白志刚,张    洁,徐    瑞,陈光勇,李文竹,张    宏,姚宏伟,张忠涛   

  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
  • 出版日期:2022-08-01 发布日期:2022-08-12

  • Online:2022-08-01 Published:2022-08-12

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-Dindo Ⅱ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。

关键词: 直肠癌, 新辅助治疗, 免疫检查点抑制剂

Abstract: Exploration of neoadjuvant chemoradiotherapy combined with tislelizumab for proficient mismatch repair locally advanced mid-low rectal cancer        GAO Jia-le, ZHANG Xiao, YANG Zheng-yang, et al. Department of General Surgery,Beijing Friendship Hospital,Capital Medical University,& National Clinical Research Center for Digestive Diseases,Beijing 100050, China
Corresponding authors:ZHANG Zhong-tao, E-mail:zhangzht@ccmu.edu.cn;YAO Hong-wei, E-mail:yaohongwei@ccmu.edu.cn
GAO Jia-le  and ZHANG Xiao are the first authors who contributed equally to the article
Abstract    Objective    To 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. Methods    The clinical data of pMMR locally advanced mid-low rectal cancer patients with clinical stage cT3-4N0M0 or 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 December 2021 were prospectively analyzed. The primary endpoint of the study was pathological complete response, and the incidence of adverse drug reactions, surgical safety, postoperative complication rate, and histopathological changes were analyzed. Results    All the patients completed chemoradiotherapy, 10 patients received 3 cycles of tislelizumab, and 1 patient received 2 cycles. One patient had the Grade 3 adverse reaction of immune-related colitis (9.1%). Sphincter-preserving surgery was performed in all patients (100%). One patient developed Clavien-Dindo II anastomotic leakage after surgery. All the patients had pMMR tumors. A total of 6 patients achieved pathological complete response (54.5%), and 3 patients achieved major pathological response (27.3%), with an objective response rate of 100.0%. Among the 6 patients with pathological complete response, 2 patients achieved clinical complete response (18.2%). Conclusion    Chemoradiotherapy combined with PD-1 antibody therapy in patients with pMMR locally advanced mid-low rectal cancer has good safety and effectiveness, and does not increase the complication rate of surgery. Follow-up studies with larger samples are needed to be further verified.

Key words: rectal neoplasm, neoadjuvant therapy, immune checkpoint inhibitor