立体定向体放射治疗（SBRT）与免疫检查点抑制剂（ICIs）相结合在晚期非小细胞肺癌（NSCLC）患者中正积极探索。然而，对于该场景中的最佳分割和放射疗法靶病变尚知之甚少。本研究调查了接受ICIs的晚期NSCLC患者的SBRT对多种器官病变的影响以及放射治疗剂量分数方案对患者预后的影响。本研究在我们的机构回顾性分析了从2015年12月至2021年9月接受ICIs和SBRT连续治疗的晚期NSCLC患者的病历。患者根据放射治疗部位分组。使用Kaplan-Meier方法记录无进展生存（PFS）和总生存（OS），并使用log-rank（Mantel-Cox）检验比较不同治疗组之间的差异。本研究确定了124例接受ICIs结合SBRT的晚期NSCLC患者。放射治疗部位包括肺部病变（肺组，n=43）、骨转移（骨组，n=24）和脑转移（脑组，n=57）。与脑组相比，肺组的平均PFS（mPFS）显着延长了13.3个月（8.5个月vs.21.8个月，HR=0.51，95％CI：0.28-0.92，P=0.0195），骨组延长了9.5个月，并且患病进展的风险降低了43％（8.5个月vs.18.0个月，HR=0.57，95％CI：0.29-1.13，P=0.1095）。与骨组相比，肺组的mPFS延长了3.8个月。肺组和骨组的平均OS（mOS）长于脑组，死亡风险降低了多达60％，低于脑组。当SBRT与ICIs同时给予时，肺组和脑组的mPFS显着长于骨组（29.6个月vs.16.5个月vs.12.1个月）。当SBRT与每份8-12 Gy结合ICIs时，与骨组和脑组相比，肺组的mPFS显着延长（25.4个月vs.15.2个月vs.12.0个月）。在接受肺部病变SBRT和脑转移的患者中，同时组的mPFS长于SBRT→ICIs组（29.6个月vs.11.4个月，P=0.0003和12.1个月vs.8.9个月，P=0.2559）。在接受<8Gy和8-12 Gy每份的SBRT患者中，同时组的mPFS也长于SBRT→ICIs组（20.1个月vs.5.3个月，P=0.0033和24.0个月vs.13.4个月，P=0.1311）。肺组，骨组和脑组的病情控制率分别为90.7％，83.3％和70.1％。本研究证明了将SBRT用于肺部病变与骨和脑转移搭配ICIs可改善晚期NSCLC患者的预后。这种改善与放射治疗与ICIs结合的顺序和放疗分割方案有关。每份8-12 Gy的放疗分割方案以及以肺部病变为靶向治疗可能是接受ICIs结合SBRT的晚期NSCLC患者的合适选择。© 2023.华中科技大学。

The combination of stereotactic body radiation therapy (SBRT) and immune checkpoint inhibitors (ICIs) is actively being explored in advanced non-small-cell lung cancer (NSCLC) patients. However, little is known about the optimal fractionation and radiotherapy target lesions in this scenario. This study investigated the effect of SBRT on diverse organ lesions and radiotherapy dose fractionation regimens on the prognosis of advanced NSCLC patients receiving ICIs.The medical records of advanced NSCLC patients consecutively treated with ICIs and SBRT were retrospectively reviewed at our institution from Dec. 2015 to Sep. 2021. Patients were grouped according to radiation sites. Progression-free survival (PFS) and overall survival (OS) were recorded using the Kaplan-Meier method and compared between different treatment groups using the log-rank (Mantel-Cox) test.A total of 124 advanced NSCLC patients receiving ICIs combined with SBRT were identified in this study. Radiation sites included lung lesions (lung group, n=43), bone metastases (bone group, n=24), and brain metastases (brain group, n=57). Compared with the brain group, the mean PFS (mPFS) in the lung group was significantly prolonged by 13.3 months (8.5 months vs. 21.8 months, HR=0.51, 95%CI: 0.28-0.92, P=0.0195), and that in the bone group prolonged by 9.5 months with a 43% reduction in the risk of disease progression (8.5 months vs. 18.0 months, HR=0.57, 95%CI: 0.29-1.13, P=0.1095). The mPFS in the lung group was prolonged by 3.8 months as compared with that in the bone group. The mean OS (mOS) in the lung and bone groups was longer than that of the brain group, and the risk of death decreased by up to 60% in the lung and bone groups as compared with that of the brain group. When SBRT was concurrently given with ICIs, the mPFS in the lung and brain groups were significantly longer than that of the bone group (29.6 months vs. 16.5 months vs. 12.1 months). When SBRT with 8-12 Gy per fraction was combined with ICIs, the mPFS in the lung group was significantly prolonged as compared with that of the bone and brain groups (25.4 months vs. 15.2 months vs. 12.0 months). Among patients receiving SBRT on lung lesions and brain metastases, the mPFS in the concurrent group was longer than that of the SBRT→ICIs group (29.6 months vs. 11.4 months, P=0.0003 and 12.1 months vs. 8.9 months, P=0.2559). Among patients receiving SBRT with <8 Gy and 8-12 Gy per fraction, the mPFS in the concurrent group was also longer than that of the SBRT→ICIs group (20.1 months vs. 5.3 months, P=0.0033 and 24.0 months vs. 13.4 months, P=0.1311). The disease control rates of the lung, bone, and brain groups were 90.7%, 83.3%, and 70.1%, respectively.The study demonstrated that the addition of SBRT on lung lesions versus bone and brain metastases to ICIs improved the prognosis in advanced NSCLC patients. This improvement was related to the sequence of radiotherapy combined with ICIs and the radiotherapy fractionation regimens. Dose fractionation regimens of 8-12 Gy per fraction and lung lesions as radiotherapy targets might be the appropriate choice for advanced NSCLC patients receiving ICIs combined with SBRT.© 2023. Huazhong University of Science and Technology.