立体定向放疗联合贝伐珠单抗及PD-1免疫治疗对非小细胞肺癌脑转移的疗效分析

Analysis of the efficacy of stereotactic radiotherapy combined with bevacizumaband PD - 1 immunotherapy on brain metastases of non - small cell lung cancer

目的:探讨立体定向放疗(stereotactic radiotherapy, SRT)联合贝伐珠单抗及程序性死亡受体1(programmed cell death-1,PD-1)免疫治疗方案在晚期非鳞非小细胞肺癌(non-squamous non-small cell lung cancer, ns-NSCLC)脑转移(brain metastases, BM)患者中的疗效和不良事件(adverse event, AE)。方法:回顾性收集中国人民解放军联勤保障部队第九〇四医院和江南大学附属医院于2019年5月至2021年12月收治的119例ns-NSCLC BM患者的临床资料,并继续随访。根据疗法分为3组:SP组:SRT+化疗;SBIP组:SRT+贝伐珠单抗+PD-1抑制剂免疫治疗+化疗;SBI组:SRT+贝伐珠单抗+PD-1抑制剂免疫治疗。比较各组的短期疗效、生存期及AE。进行亚组分析探索,并对试验进行危险因素分析。结果:SBIP组、SBI组在疾病控制率(disease control rate, DCR)、无进展生存期(progress-free survival, PFS)和总生存期(overall survival, OS)上差异无统计学意义,但均优于SP组,差异有统计学意义,SBI组在AE分级上与SBIP组有统计学差异,且AE发生率低于SBIP组。年龄、分化程度、治疗方案、体力状态(performance status, PS)评分、脑膜转移、程序性死亡受体配体1(programmed cell death-ligand 1,PD-L1)表达水平、确诊BM时肺原发灶直径为ns-NSCLC BM患者预后的独立危险因素。在亚组分析中,表皮生长因子受体(epidermal growth factor receptor, EGFR)阳性组与阴性组在OS上差异无统计学意义。结论:SRT联合贝伐珠单抗和免疫治疗能有效提升ns-NSCLC BM患者的疗效,且AE较少,安全性更高。

Objective:To investigate the efficacy and adverse reactions of stereotactic radiotherapy(SRT)combined with bevacizumab and programmed cell death-1(PD-1)inhibitor immunotherapy in patients with brain metastases(BM)from advanced non-squamous non-small cell lung cancer(ns-NSCLC).Methods:Clinical data of 119 patients with non-squamous non-small cell lung cancer brain metastasis treated at the 904th Hospital of the Joint Logistics Support Force of PLA and the Affiliated Hospital of Jiangnan University from May 2019 to December 2021 were retrospectively collected and followed up.They were divided into 3 groups according to therapies:Group SP: SRT + chemotherapy, group SBIP: SRT + chemotherapy + bevacizumab + PD - 1 inhibitor immunotherapy, groupSBI: SRT + bevacizumab + PD - 1 inhibitor immunotherapy. The short - term efficacy, survival period, and adversereactions of each group were compared pairwise. Risk factor analysis was performed on the trial. Results: There wasno statistically significant difference in disease control rate ( DCR) ,progress - free survival ( PFS) ,and overallsurvival ( OS) between group SBIP and group SBI,but both were superior to group SP. Group SBI had a significantdifference in adverse reaction grading compared to group SBIP,and the incidence of adverse reactions was lowerthan that of group SBIP. Age,differentiation grade,performance status ( PS) score,meningeal metastasis,programmedcell death - ligand 1( PD - L1) expression level and biggest size of lung cancer were independent riskfactors for patients in ns - NSCLC BM. In subgroup analyses, the difference in OS between the epidermal growthfactor receptor( EGFR) positive and negative groups was not statistically significant. Conclusion: Stereotactic radiotherapycombined with antiangiogenic targeted therapy and immunotherapy can effectively improve the efficacy ofpatients in ns - NSCLC with brain metastasis,with few adverse reactions and high safety,which is worthy of clinicalpromotion and application.