晚期非小细胞肺癌免疫治疗的失败模式及联合放疗的预后

The failure mode after immunotherapy and clinical prognosis of combined radiotherapy for metastatic non-small cell lung cancer

目的探讨晚期非小细胞肺癌(NSCLC)一线免疫治疗后的失败模式及联合放疗对患者预后的影响.方法回顾性分析2017年1月至2021年12月于天津医科大学肿瘤医院接受一线免疫检查点抑制剂(ICI)治疗的220例晚期NSCLC患者资料,收集患者的基线特征、一线治疗方案、失败原因及部位、放疗目的、部位及处方剂量.主要观察指标是总生存(OS)期.采用Kaplan-Meier法进行生存分析,采用log-rank检验比较生存情况.结果共纳入晚期NSCLC患者220例,其中65例(29.5%)初诊呈现寡转移状态.在72例接受放疗的患者中,胸部放疗29例(40%)、转移灶放疗53例(74%).全组患者中位随访时间为25.6个月.截至末次随访,140例患者已出现病情进展,其中84例(38.2%)患者呈现寡进展状态.在已出现病情进展且能够明确进展部位的120例患者中,62例(51.7%)患者一线免疫治疗失败原因为原有病灶出现进展(主要在胸腔内),34例(28.3%)患者的治疗失败源于新转移灶的出现,其余24例(20.0%)为同时出现原有病灶进展和新发远处转移.在接受一线免疫治疗联合局部放疗的72例患者中,17例(24%)接受了计划性放疗,另17例(24%)的放疗为挽救性,其余38例(53%)放疗的目的是缓解症状.患者预后因放疗目的不同而呈现显著差异(P=0.030),未接受放疗的患者中位OS期为29.1个月,接受计划性放疗的患者为未达到,行挽救性放疗的患者为28.7个月,而为缓解症状行局部放疗的患者仅为19.0个月.结论一线免疫治疗的主要失败原因为原有病灶出现进展,肿瘤进展的主要部位为胸腔内.针对胸腔内病灶的局部治疗有在一线免疫治疗的基础上进一步为晚期NSCLC患者带来生存获益的趋势.

Objective To analyze the failure mode after immunotherapy and the prognostic significance of combined radiotherapy for advanced non-small cell lung cancer(NSCLC).Methods Clinical data of 220 advanced NSCLC patients receiving immune checkpoint inhibitors(ICI)as the first-line therapy in Tianjin Medical University Cancer Institute and Hospital from January 2017 to December 2021 were retrospectively analyzed.The baseline characteristics,the first-line treatment regimen,modes and locations of failure,radiotherapy purpose,location and prescription dose of all patients were collected.The main parameter was the overall survival(OS).Survival analysis was conducted by Kaplan-Meier method.Survival comparison was performed by log-rank test.Results A total of 220 patients were enrolled in the study in which 65 cases(29.5%)exhibited a state of oligometastasis.Among 72 patients who received radiotherapy,29 cases(40%)received chest radiotherapy and 53 cases(74%)received metastatic radiotherapy.The median follow-up time was 25.6 months.Up to the last follow-up,disease progression had been observed in 140 patients,with 84 patients(38.2%)of them demonstrating a state of oligometastasis.Among 120 patients with disease progression and confirmed location of progression,62 patients(51.7%)failed in first-line immunotherapy because of the primary lesion progression(mainly in the chest cavity),34 patients(28.3%)due to the appearance of new metastases,and the remaining 24 patients(20.0%)due to primary lesion progression and new distant metastases.Among 72 patients treated with the first-line immunotherapy combined with local radiotherapy,17 patients(24%)received planned radiotherapy,another 17 patients(24%)received salvage radiotherapy,and the remaining 38 patients(53%)received radiotherapy to relieve symptoms.The prognosis of patients significantly differed according to the purpose of radiotherapy(P=0.030).The median OS of patients who did not receive radiotherapy was 29.1 months,those who received planned radiotherapy did not reach the median OS,and the median OS of those who received salvage radiotherapy was 28.7 months,and the median OS of those who received local radiotherapy to relieve symptoms was only 19.0 months.Conclusions The progression of primary lesions is the main failure mode of the first-line immunotherapy.Chest cavity is the main location of tumor progression.Local radiotherapy for intrathoracic lesions may improve the survival benefit further for advanced NSCLC patients after the first-line immunotherapy.