放疗序贯免疫治疗Ⅲ期非小细胞肺癌的真实世界研究  

A real-world study of radiotherapy sequential immunotherapy for stage III non-small cell lung cancer

作　　者：黄丛秀 王少军[2] 林宇[1] 孙晓革[1] 郁志龙[1] 杨昊 何占彪[1] Huang Congxiu;Wang Shaojun;Lin Yu;Sun Xiaoge;Yu Zhilong;Yang Hao;He Zhanbiao(Department of Radiotherapy,the Affiliated Hospital of Inner Mongolia Medical University,Hohhot010050,China;Department of Medical Oncology,the Affiliated Hospital of Inner Mongolia Medical University,Hohhot010050,China;Radiotherapy Center,Inner Mongolia Branch of Peking University Cancer Hospital,Hohhot010050,China)

机构地区：[1]内蒙古医科大学附属医院放疗科,呼和浩特010050 [2]内蒙古医科大学附属医院肿瘤内科,呼和浩特010050 [3]北京大学肿瘤医院内蒙古医院放疗中心,呼和浩特010050

出　　处：《中华放射肿瘤学杂志》2025年第1期57-64,共8页Chinese Journal of Radiation Oncology

基　　金：内蒙古自治区科技计划项目(2016MKJ0023);内蒙古医科大学附属医院青年探索项目(2022NYFYTS008)。

摘　　要：目的探索真实世界中放疗序贯免疫治疗对不可切除Ⅲ期非小细胞肺癌(NSCLC)患者生存时间和免疫功能的影响。方法收集2021年1月至2022年12月(回顾性队列)和2023年1月至2023年12月(前瞻性队列)于内蒙古医科大学附属医院治疗的84例不可切除的Ⅲ期NSCLC患者的资料。根据患者是否进行序贯免疫治疗,分为联合组(40例)和放疗组(44例),通过标准化死亡比加权法(SMRW)比较两组患者的无进展生存(PFS)期和总生存(OS)期。采用Cox比例风险单因素、多因素回归分析、倾向性评分多模型比较和亚组分析进行两组间疗效稳健性分析,采用E值分析对观察性研究的未测量混杂因素进行敏感性分析。通过协方差分析比较两组患者治疗前后CD4^(+)T细胞百分比、CD8^(+)T细胞百分比、自然杀伤(NK)细胞百分比和CD4^(+)/CD8^(+)T细胞比值。结果84例患者中,男性77例(92%),女性7例(8%);年龄≥65岁42例(50%)。SMRW后变量高度同质化,标准化平均差<0.1。在SMRW调整前后,患者的中位PFS期和OS期,联合组均显著高于放疗组,差异有统计学意义。SMRW调整后,PFS期为17.0比7.0个月,HR=0.260,95%CI为0.130~0.490,P<0.001,OS期为未达到比24.0个月,HR=0.210,95%CI为0.070~0.590,P=0.002。稳健性分析和敏感性分析证实研究结果可靠。治疗后,与放疗组相比联合组的CD4^(+)T细胞百分比、NK细胞百分比和CD4^(+)/CD8^(+)T细胞比值均显著升高,CD8^(+)T细胞百分比显著降低,差异均有统计学意义(均为P<0.05)。结论对于不可手术切除的Ⅲ期NSCLC患者,放疗后序贯免疫治疗可显著改善其生存预后,其中联合化疗生存获益更佳,生存获益的主要机制可能是抗肿瘤免疫功能的改善。Objective To evaluate the effects of sequential immunotherapy with radiotherapy on survival time and immune function in patients with unresectable stage III non-small cell lung cancer(NSCLC)in a real-world study.MethodsData of 84 patients with unresectable stage III NSCLC who were treated at the Affiliated Hospital of Inner Mongolia Medical University from January 2021 to December 2022(retrospective cohort)and from January 2023 to December 2023(prospective cohort)were collected.The patients were divided into the combination group(n=40)and radiotherapy group(n=44)based on whether they received sequential immunotherapy or not.The progression-free survival(PFS)and overall survival(OS)between two groups were compared using standardized mortality ratio weighting(SMRW).Univariate Cox proportional hazards model,multivariate regression analysis,multi-model comparison of propensity score matching and subgroup analysis were emploed to analyze the robustness of clinical efficacy between two groups.E-value analysis was used to analyze the sensitivity of unmeasured confounding factors in observational studies.Additionally,the percentage of CD4^(+)T cells,CD8^(+)T cells and natural killer(NK)cells,and CD4^(+)/CD8^(+)T cell ratio before and after treatment between two groups were compared using analysis of covariance.ResultsAmong 84 patients,77(92%)cases were male and 7(8%)were female.Among them,42(50%)were aged 65 years or older.The variables showed high homogeneity after SMRW,with a standardized mean difference of less than 0.1.In the combination group,the median PFS[17.0 months vs.7.0 months,HR=0.260,95%CI:0.130-0.490,P<0.001]and OS[not reached vs.24.0 months,HR=0.210,95%CI:0.070-0.590,P=0.002]were significantly longer compared to that in the radiotherapy group,with statistically significant differences.The study results were confirmed by robustness and sensitivity analyses.After treatment,patients in the combination group showed a statistically significant increase in the percentage of CD4^(+)T cells and NK cells,and CD4^(+

关 键 词：癌 非小细胞肺 免疫疗法 放射疗法 治疗效果 淋巴细胞亚群 

分 类 号：R734.2[医药卫生—肿瘤]