直肠癌新辅助免疫治疗相关不良反应分析:一项全国多中心回顾性研究  

Adverse events of neoadjuvant immunotherapy for rectal cancer:a nationwide multicenter retrospective study

作　　者：邱小原 孙丽婷 王晨童 姚宏伟[2] 王权[3] 周爱萍[4] 吴小剑[5] 张卫 周雷[7] 周皎琳[1] 林国乐[1] QIU Xiao-yuan;SUN Li-ting;WANG Chen-tong(Department of General Surgery,Peking Union Medical College Hospital,Peking Union Medical College,Chinese Academy of Medical Sciences,Beijing 100730,China;不详)

机构地区：[1]中国医学科学院北京协和医学院,北京协和医院基本外科,北京100730 [2]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 [3]吉林大学第一医院胃肠外科,吉林长春130021 [4]中国医学科学院肿瘤医院肿瘤内科,北京100021 [5]中山大学附属第六医院结直肠肛门外科,广东广州510655 [6]海军军医大学第一附属医院(上海长海医院)肛肠外科,上海200433 [7]中日友好医院胃肠外科,北京100029

出　　处：《中国实用外科杂志》2024年第7期787-792,共6页Chinese Journal of Practical Surgery

基　　金：中央高水平医院临床科研专项项目(No.2022-PUMCH-C-005);中国医学科学院医学与健康科技创新工程项目(No.2022-I2M-C&T-B-032)。

摘　　要：目的分析直肠癌病人接受新辅助免疫检查点抑制剂(ICIs)治疗发生免疫相关不良反应(irAEs)情况,并探讨其管理策略。方法回顾性分析2020年9月至2024年3月全国7家中心收治的100例接受新辅助免疫治疗后发生irAEs的直肠癌病人的临床资料。收集并分析基线资料、新辅助治疗方案、irAEs诊断及治疗情况、手术情况及随访资料。结果新辅助治疗期间,irAEs的总发作次数为141次,32例(32%)病人发生irAEs次数>1次。irAEs主要发生在内分泌系统、肝脏、皮肤、胃肠道和骨关节与肌肉,分别为41次、33次、29次、17次和7次,中位发生时间分别为31、18、12、32.5、29 d。Ⅰ、Ⅱ级irAEs发生131次(92.9%),经保守治疗、对症处理后好转;≥Ⅲ级的irAEs发生10次(7.1%),经多学科综合治疗协作组(MDT)评估后,予糖皮质激素、免疫抑制剂等治疗后好转,其中7例病人永久停止ICIs治疗,3例病人继续ICIs治疗。irAEs严重程度与是否联合放疗无关(P=0.858)。5例(5%)病人出现延迟性irAEs。新辅助治疗后3例(3%)临床完全缓解病人行等待观察策略,97例(97%)病人行手术治疗。发生手术相关并发症11例(11.3%)。术后中位随访时间为12个月,97例(97%)病人无病生存,1例(1%)病人出现肿瘤复发,2例(2%)病人出现肿瘤远处转移。结论直肠癌新辅助免疫治疗中存在发生1次或多次irAEs的可能,且内分泌系统、肝脏和皮肤是最常受累的系统或器官。多数irAEs可通过对症治疗缓解。对于发生≥Ⅲ级irAEs的病人,应通过MDT讨论制定诊疗计划,且多数病人需永久停用ICIs。另外,irAEs严重程度与是否联合放疗无关,经过治疗后的irAEs并不影响病人手术安全,但须警惕irAEs延迟发生。To analyze the immune-related adverse events(irAEs)and their management strategies in patients with rectal cancer receiving neoadjuvant immune checkpoint inhibitors(ICIs)therapy.Methods We conducted a retrospective study,including 100 rectal cancer patients who underwent irAEs after neoadjuvant immune therapy between September 2020 and March 2024 at seven centers nationwide.Baseline data,neoadjuvant treatment regimens,irAEs diagnosis and treatment,surgical outcomes,and follow-up information were collected.Results During neoadjuvant treatment,there were a total of 141 episodes of irAEs,with 32 patients(32%)experiencing more than one irAE.irAEs mainly occurred in the endocrine system,liver,skin,gastrointestinal tract,and musculoskeletal system,with 41,33,29,17and 7 times,respectively,and the median time of irAEs occurrence in each system was 31,18,12,32.5 and 29 days,respectively.Grade I andⅡirAEs occurred 131 times(92.9%),which could be managed with conservative treatment and symptomatic management.Grade III and above irAEs occurred 10 times(7.1%),and after evaluation by a multi-disciplinary team(MDT),applying treatment such as glucocorticoids,immunosuppressants,and so on,ameliorated irAEs.Among them,7 patients permanently discontinued ICIs treatment,and 3 patients continued ICIs treatment.The severity of irAEs was not associated with whether patients received combined radiotherapy(P=0.858).Delayed irAEs occurred in 5 cases(5%).3 patients(3%)with clinical complete remission after neoadjuvant treatment opted for Watch&Wait strategy,while 97 patients(97%)underwent surgical treatment.11 cases(11.3%)had surgery-related complications.The median follow-up time after surgery was 12 months.Among the cases,97 patients(97%)achieved disease-free survival,1 patient(1%)experienced tumor recurrence,and 2 patients(2%)developed distant metastases.Conclusion There is a possibility of one or multiple irAEs occurring in neoadjuvant immunotherapy for rectal cancer,with the endocrine system,liver,and skin being the most commonly aff

关 键 词：直肠癌 免疫治疗 免疫检查点抑制剂 免疫相关不良反应 

分 类 号：R6[医药卫生—外科学]