目的 探讨颅脑放疗（RT）联合免疫治疗对非小细胞肺癌（NSCLC）伴脑转移患者的疗效及程序性死亡配体1(PDL1)表达水平对其预后的影响。方法 回顾性收集2019年1月—2024年12月在内蒙古自治区人民医院接受RT联合免疫治疗的NSCLC脑转移患者，按治疗时序分为同步组（放疗与免疫治疗启动间隔≤2周）和序贯组（放疗结束后>2周启动免疫治疗），根据肿瘤比例评分（TPS）值将PD-L1分为阳性组（≥1%组）和阴性组（<1%组）。比较4个亚组的颅内局部控制率（i LC）、颅内无进展生存期（i PFS）、总生存期（OS）及神经毒性（放射性坏死、免疫相关脑炎）发生率，采用Cox回归分析生存预后因素，采用Logistic回归分析神经毒性风险因素。结果 共纳入46例患者，同步组26例，序贯组20例；PD-L1阳性组20例，阴性组26例。同步治疗组中位OS显著优于序贯组（28.20个月vs 24.95个月，P=0.012）。PD-L1阳性+同步组OS达34.70个月，但该亚组神经毒性发生率较高（55.6%）。结论 放疗与免疫治疗同时应用（≤2周）可提高NSCLC伴脑转移患者的iLC、iPFS及OS。放疗与免疫治疗的时序与PD-L1表达存在协同关联，PD-L1阳性患者可能获益更多但面临神经毒性风险。本研究为临床优化免疫联合放疗策略、平衡疗效与毒性提供了探索性证据。

Objective To investigate the efficacy of cranial radiotherapy(RT) combined with immunotherapy in patients with nonsmall cell lung cancer(NSCLC) and brain metastases, and to explore the prognostic impact of programmed death-ligand 1(PD-L1) expression levels. Methods NSCLC patients with brain metastases who received cranial radiotherapy combined with immunotherapy was retrospectively enrolled from Inner Mongolia People's Hospital from January 2019 to December 2024. Patients were divided into the concurrent group(interval between immunotherapy and radiotherapy ≤ 2 weeks) and the sequential group(immunotherapy initiated > 2 weeks after radiotherapy completion) according to the treatment sequence. Based on the tumor proportion score(TPS), PD-L1 expression was divided into the positive group(≥ 1%) and the negative group(< 1%). The intracranial local control rate(iLC), intracranial progression-free survival(iPFS), overall survival(OS), and incidence of neurotoxicity(radiation necrosis, immune-related encephalitis) were compared among the four subgroups. Cox regression analysis was used to identify prognostic factors for survival, and Logistic regression analysis was applied to analyze risk factors for neurotoxicity. Results A total of 46 patients were enrolled, including 26 in the concurrent group and 20 in the sequential group; Twenty in the PD-L1 positive group and 26 in the PD-L1 negative group. The median OS in the concurrent treatment group was significantly superior to that in the sequential group(28.20 months vs 24.95 months, P = 0.012). The OS of the PD-L1 positive + concurrent subgroup reached 34.70 months, but the incidence of neurotoxicity in this subgroup was higher(55.6%). Conclusion Concurrent administration of radiotherapy and immunotherapy(≤ 2 weeks) can improve iLC, iPFS, and OS in NSCLC patients with brain metastases. There is an interaction between the timing of radiotherapy and immunotherapy and PD-L1 expression. Patients with positive PD-L1 may benefit more but face an increased risk of neurotoxicity. This study provides exploratory evidence for clinically optimizing the strategy of immunoradiotherapy and balancing efficacy and toxicity.

R965

北京肿瘤防治研究会“CAPTRA-Lung科研基金”项目(CAPTRA-Lung2022001); 中央引导地方科技发展资金项目(2024ZY0152); 内蒙古自治区医师协会临床医学研究和临床新技术推广项目(YSXH2024KYD03); 北京肿瘤防治研究会“CAPTRA-Lung科研基金”项目(CAPTRA-Lung2022002)