胃癌术前免疫治疗的疗效及安全性初探:一项回顾性病例系列研究

Efficacy and safety after preoperative immunotherapy for gastric cancer:a retrospective case series study

目的探讨胃癌术前免疫治疗的有效性及安全性。方法采用回顾性病例系列的研究方法,按照纳入、排除标准,收集2019年4月至2021年11月间在北京大学肿瘤医院胃肠肿瘤中心一病区行手术治疗的胃癌病人的临床资料,评估术前免疫治疗后病人治疗不良事件的发生率及严重不良事件的发生率;术后恢复情况,包括肛门排气时间、排便时间、流食时间、半流食时间、术后住院时间;术后并发症的发生率及严重并发症的发生率;以及客观缓解率(objective response rate,ORR),疾病控制率(disease control rate,DCR),病理完全缓解(pathological complete response,pCR),显著病理缓解(major pathological response,MPR)等指标。结果共纳入52例病人。术前治疗安全性方面,34例(65.4%)病人发生Ⅰ~Ⅱ级不良事件,Ⅲ级以上不良事件发生率为7.7%(4/52)。术后恢复方面,病人术后中位首次肛门排气时间为3.5 d(1~8 d);中位首次排便时间为5 d(2~11 d);中位首次进流食时间为4 d(2~10 d);中位首次进半流食时间为6.5 d(5~18 d);中位术后住院时间为11 d(3~60 d)。手术安全性方面,21例(40.3%)病人发生术后并发症,2例(3.8%)病人发生Ⅲ级以上并发症。疗效评价方面,免疫治疗后的ORR为34.6%(18/52),DCR为94.2%(49/52),R0切除率为90.4%(47/52),MPR病人19例(36.5%),pCR病人12例(23.1%),其中错配修复缺陷(mismatch repair deficient,dMMR)或微卫星高度不稳定(microsatellite instability-high,MSI-H)病人的pCR率为30.0%(3/10),错配修复正常(mismatch repair proficient,pMMR)或微卫星稳定(microsatellite stability,MSS)病人的pCR率为23.7%(9/38)。结论胃癌术前行免疫治疗具有较好的有效性及安全性,未显著增加手术风险,同时可获得较为理想的病理缓解率,可能是胃癌围术期安全、有效、可行的治疗模式。其有效性及安全性仍需大规模对照研究进行进一步验证。

Objective To explore the efficacy and safety of preoperative immunotherapy for gastric cancer.Methods A retrospective case series was constructed on the basis of the inclusion and exclusion criteria.Clinical data were reviewed for 52 surgical patients of gastric cancer from April 2019 to November 2021.The incidence of adverse events and serious adverse events after immunotherapy,postoperative recovery parameters including time to initial flatus&defecation,time to fluid&semi-fluid diet,postoperative hospital stay,incidence of postoperative complications,serious complications and therapeutic efficacy parameters including objective response rate(ORR),disease control rate(DCR),pathological complete response(pCR)and major pathological response(MPR)were evaluated.Results In terms of safety of preoperative immunotherapy,34 patients(65.4%)had gradeⅠ-Ⅱadverse events and the incidence of serious adverse events was 7.7%(4/52).In terms of postoperative recovery,the median time to initial flatus was 3.5(1-8)days,time to initial defecation 5(2-11)days,time of fluid diet 4(2-10)days and time to semi-fluid diet 6.5(5-18)days.The median postoperative hospital stay was 11(3-60)days.In terms of surgical safety,postoperative complications occurred in 21 patients(40.3%)and gradeⅢor higher complications in 2 patients(3.8%).In terms of efficacy evaluation,ORR after immunotherapy was 34.6%(18/52),DCR 94.2%(49/52)and R0 resection rate 90.4%(47/52).The rate of MPR and pCR was 36.5%(19/52)and 23.1%(12/52)respectively.The rate of pCR in patients with dMMR or MSI-H was 30.0%(3/10)and those with pMMR or MSS 23.7%(9/38).Conclusion Preoperative immunotherapy for gastric cancer has an acceptable efficacy and safety.Without a higher surgical risk,it yields a relatively ideal pathological response rate.It may be a safe,effective and feasible perioperative treatment for gastric cancer.Large-scale controlled studies are still required for further verifying its efficacy and safety.