放疗联合PD-1抑制剂治疗驱动基因阴性非小细胞肺癌脑转移患者的疗效分析  

Prognostic analysis of radiotherapy combined with PD-1 inhibitors in patients with driver-gene negative non-small cell lung cancer and brain metastases

作　　者：张献文 孙谦 蔡丰 赵梦蝶 宋世龙 陈如君 江浩 ZHANG Xianwen;SUN Qian;CAI Feng;ZHAO Mengdie;SONG Shilong;CHEN Rujun;JIANG Hao(Department of Radiotherapy,the First Affiliated Hospital of Bengbu Medical University,Bengbu,Anhui 233004,China)

机构地区：[1]蚌埠医科大学第一附属医院放疗科,安徽蚌埠233004

出　　处：《中华全科医学》2024年第12期2016-2019,2157,共5页Chinese Journal of General Practice

基　　金：国家自然科学基金项目(82403993);蚌埠医学院自然科学重点项目(2021byzd159);安徽省临床医学研究转化专项项目(202304295107020078)。

摘　　要：目的观察颅脑放疗(RT)与程序性死亡受体1(PD-1)抑制剂联合治疗在驱动基因阴性非小细胞肺癌(NSCLC)伴脑转移(BMs)患者中的疗效及不良反应,探讨其临床应用价值。方法收集2021年1月—2023年7月蚌埠医科大学第一附属医院接受RT的90例NSCLC伴BMs患者,根据是否联合PD-1抑制剂治疗分为放疗组(40例)和联合组(50例)。采用Kaplan-Meier方法和Cox回归模型评估颅内近期疗效、颅内局部无进展生存(iLPFS)、颅内远处无进展生存(iDPFS)和总生存(OS)。结果随访至2024年7月,放疗组和联合组的颅内客观缓解率(iORR)分别为45.0%(18/40)和72.0%(36/50,P=0.009);放疗组和联合组中位iLPFS、iDPFS、OS分别11个月(95%CI:8.77~13.23)、14个月(95%CI:7.69~20.31)、14个月(95%CI:11.98~16.02)和22个月(95%CI:18.23~25.77)、21个月(95%CI:13.24~28.76)、21个月(95%CI:17.63~24.37),差异均有统计学意义(P<0.05)。单因素与多因素分析显示,联合PD-1抑制剂治疗是影响iLPFS与iDPFS的独立预后因素。分层分析显示,放疗尽早介入,尤其是放疗与PD-1抑制剂同步治疗(≤2周)的患者具有更优的iLPFS(P=0.007)和iDPFS(P=0.027),但OS差异无统计学意义(P=0.385)。2组患者不良反应均可耐受。结论RT联合PD-1抑制剂治疗,尤其是RT与PD-1抑制剂同时应用(≤2周)可提高驱动基因阴性NSCLC伴BMs患者的iLPFS、iDPFS,有利于改善OS。Objective Observation of the efficacy and adverse reactions of combined treatment of cranial radiation therapy(RT)and programmed death-1(PD-1)inhibitors in patients with driver gene negative non-small cell lung cancer(NSCLC)with brain metastases(BMs),and exploration of its clinical application value.Methods A total of 90 NSCLC BM patients who received RT at the First Affiliated Hospital of Bengbu Medical University from January 2021 to July 2023 were included.They were divided into the radiotherapy group(40 cases)and the combination group(50 cases),based on whether they were treated with PD-1 inhibitors.Kaplan-Meier method and Cox regression model were used to evaluate intracranial short-term efficacy,intracranial local progression free survival(iLPFS),intracranial distant progression free survival(iDPFS),and overall survival(OS).Results By July 2024,the intracranial objective response rate(iORR)was 45.0%and 72.0%in the radiotherapy group and the combination group,respectively(P=0.009).The median iLPFS,iDPFS,and OS for the radiotherapy group were 11 months(95%CI:8.77-13.23),14 months(95%CI:7.69-20.31),and 14 months(95%CI:11.98-16.02),respectively.In the combination group,the corresponding medians were 22 months(95%CI:18.23-25.77),21 months(95%CI:13.24-28.76),and 21 months(95%CI:17.63-24.37),respectively,with statistically significant differences(P<0.05).Univariate and multivariate analysis showed that combined PD-1 inhibitor therapy is an independent prognostic factor for iLPFS and iDPFS.Stratified analysis showed that early intervention of RT,especially when synchronized with PD-1 inhibitors(≤2 weeks),resulted in significantly improved iLPFS(P=0.007)and iDPFS(P=0.027),though no statistically significant difference was observed in OS(P=0.385).Both groups of patients tolerated adverse reactions.Conclusion The combination therapy of RT and PD-1 inhibitors,especially when administered simultaneously(≤2 weeks),improves iLPFS and iDPFS in patients with driver gene-negative NSCLC BMs,contributing to improved OS.

关 键 词：非小细胞肺癌 脑转移 放疗 程序性死亡受体1抑制剂 

分 类 号：R734.2[医药卫生—肿瘤] R730.58[医药卫生—临床医学]