Introduction: Intracranial metastases are a common cause of morbidity and mortality in patients with advanced NSCLC, and are frequently managed with radiation therapy (RT). The safety of cranial RT in the setting of treatment with immune checkpoint inhibitors (ICIs) has not been established. Methods: We identified patients with advanced NSCLC with brain metastases who received cranial RT and were treated with or without programmed cell death 1/programmed death ligand 1 inhibitors between August 2013 and September 2016. RT‐related adverse events (AEs) were retrospectively evaluated and analyzed according to ICI treatment status, cranial RT type, and timing of RT with respect to ICI. Results: Of 163 patients, 50 (31%) received ICIs, whereas 113 (69%) were ICI naive. Overall, 94 (58%), 28 (17%), and 101 (62%) patients received stereotactic radiosurgery, partial brain irradiation, and/or whole brain RT, respectively. Fifty percent of patients received more than one radiation course. We observed no significant difference in rates of all‐grade AEs and grade 3 or higher AEs between the ICI‐naive and ICI‐treated patients across different cranial RT types (grade ≥3 AEs in 8% of ICI‐naive patients versus in 9% of ICI‐treated patients for stereotactic radiosurgery [p = 1.00] and in 8% of ICI‐naive patients versus in 10% of ICI‐treated patients for whole brain RT [p = 0.71]). Additionally, there was no difference in AE rates on the basis of timing of ICI administration with respect to RT. Conclusions: Treatment with an ICI and cranial RT was not associated with a significant increase in RT‐related AEs, suggesting that use of programmed cell death 1/programmed death ligand 1 inhibitors in patients receiving cranial RT may have an acceptable safety profile. Nonetheless, additional studies are needed to validate this approach.

中文翻译：

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非小细胞肺癌联合 PD-1 通路抑制和颅内放射治疗的安全性

简介：颅内转移是晚期 NSCLC 患者发病率和死亡率的常见原因，经常通过放射治疗 (RT) 进行治疗。头颅放疗在免疫检查点抑制剂 (ICIs) 治疗中的安全性尚未确定。方法：我们确定了 2013 年 8 月至 2016 年 9 月期间接受颅骨放疗并接受或不接受程序性细胞死亡 1/程序性死亡配体 1 抑制剂治疗的晚期 NSCLC 脑转移患者。根据 ICI 治疗状态、颅内放疗类型和放疗时间对 ICI 进行分析。结果：在 163 名患者中，50 名 (31%) 接受了 ICI，而 113 (69%) 名未接受 ICI。总体而言，94 (58%)、28 (17%)、和 101 (62%) 名患者分别接受了立体定向放射外科手术、部分脑部照射和/或全脑放疗。50% 的患者接受了不止一个放射疗程。我们观察到，不同颅骨放疗类型的 ICI 初治和 ICI 治疗患者之间的所有级别 AE 和 3 级或更高级别 AE 的发生率没有显着差异（8% 的 ICI 初治患者和 9% 的 3 级 AE接受 ICI 治疗的立体定向放射外科患者 [p = 1.00] 和 8% 的 ICI 初治患者与 10% 的 ICI 治疗患者进行全脑放疗 [p = 0.71]）。此外，根据 ICI 给药的时间，相对于 RT，AE 发生率没有差异。结论：ICI 和颅内放疗与放疗相关 AE 的显着增加无关，表明在接受颅内放疗的患者中使用程序性细胞死亡 1/程序性死亡配体 1 抑制剂可能具有可接受的安全性。尽管如此，还需要更多的研究来验证这种方法。