放疗联合免疫治疗对肺癌脑转移的疗效和安全性的meta分析

Efficacy and Safety of Radiotherapy Combined with Immunotherapy for Brain Metastases from Lung Cancer:A Meta-analysis

背景与目的免疫治疗(immunotherapy,IT)被推荐用于治疗晚期非小细胞肺癌(non-small cell lung cancer,NSCLC),而脑放疗(radiation therapy,RT)是脑转移(brain metastasis,BM)患者的主流治疗方法。本研究旨在调查RT和IT联合使用的疗效及安全性。方法检索时限截至2022年5月1日,在中国知网、万方、PubMed、EMBASE、Cochranc数据库中进行了文献检索。异质性采用I2检验和P值进行判断。发表偏倚采用漏斗图评价。采用纽卡斯尔-渥太华量表(Newcastle Ottawa Scale,NOS)评估纳入研究的质量。采用Stata 16.0软件进行统计分析。结果纳入17篇文献共涉及2,636例患者。在RT+IT组和RT组的比较中,总生存期(overall survival,OS)(HR=0.85,95%CI:0.52-1.38,I^(2)=73.9%,P_(异质性)=0.001)和颅内远距离控制(distant brain control,DBC)(HR=1.04,95%CI:0.55-1.05,I^(2)=80.5%,P_(异质性)<0.001)未发现明显差异,但RT+IT组颅内控制(local control,LC)优于RT组(HR=0.46,95%CI:0.22-0.94,I^(2)=22.2%,P_(异质性)=0.276),发生放射性坏死/治疗相关影像学改变(radionecrosis/treatment related imaging changes,RN/TRIC)风险高于RT组(HR=1.72,95%CI:1.12-2.65,I^(2)=40.2%,P_(异质性)=0.153)。在RT+IT同步治疗组和序贯组的比较中,未发现OS(HR=0.62,95%CI:0.27-1.43,I^(2)=74.7%,P_(异质性)=0.003)和RN/TRIC(HR=1.72,95%CI:0.85-3.47,I^(2)=0%,P_(异质性)=0.388)在两组中存在差异。但同步治疗组DBC优于序贯治疗组(HR=0.77,95%CI:0.62-0.96,I^(2)=80.5%,P_(异质性)<0.001)。结论RT联合IT并未改善NSCLC BM患者的OS,而且还会增加RN/TRIC的风险。此外,相对于RT与IT序贯治疗,RT与IT同步治疗可改善DBC的疗效。

Background and objective Immunotherapy(IT)is recommended for the treatment of advanced non-small cell lung cancer(NSCLC),while brain radiotherapy(RT)is the mainstream treatment for patients with brain metastases(BM).This study aimed to investigate the efficacy and safety of combined use of RT and IT.Methods The date was limited to May 1,2022,and literature searches were carried out in CNKI,Wanfang,PubMed,EMBASE and Cochrane databases.Hetero-geneity was judged using the I^(2)test and P value.Publication bias was assessed using a funnel plot.The quality of included stud-ies was assessed using the Newcastle-Ottawa Scale(NOS).Statistical analysis was performed using Stata 16.0 software.Results A total of 17 articles involving 2,636 patients were included.In the comparison of RT+IT group and RT group,no significant difference was found in overall survival(OS)(HR=0.85,95%CI:0.52-1.38,I^(2)=73.9%,P_(heterogeneity)=0.001)and intracranial distance control(DBC)(HR=1.04,95%CI:0.55-1.05,I^(2)=80.5%,P_(heterogeneity)<0.001),but the intracranial control(LC)in the RT+IT group was better than the RT group(HR=0.46,95%CI:0.22-0.94,I^(2)=22.2%,P_(heterogeneity)=0.276),and the risk of radia-tion necrosis/treatment-related imaging changes(RN/TRIC)was higher than RT(HR=1.72,95%CI:1.12-2.65,I^(2)=40.2%,P_(het erogeneity)=0.153).In the comparison between the RT+IT concurrent group and the sequential group,no significant difference was found in OS(HR=0.62,95%CI:0.27-1.43,I^(2)=74.7%,P_(heterogeneity)=0.003)and RN/TRIC(HR=1.72,95%CI:0.85-3.47,I^(2)=0%,P_(heterogeneity)=0.388)was different between the two groups.However,DBC in the concurrent treatment group was better than that in the sequential treatment group(HR=0.77,95%CI:0.62-0.96,I^(2)=80.5%,Pheterogeneity<0.001).Conclusion RT combined with IT does not improve the OS of NSCLC patients with BM,but also increases the risk of RN/TRIC.In addition,compared with sequential RT and IT,concurrent RT and IT improved the efficacy of DBC.