Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts.
Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts.
J Thorac Oncol. 2018 Apr;13(4):550-558. doi: 10.1016/j.jtho.2018.01.012. Epub 2018 Jan 31.
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.
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.
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.
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.
颅内转移是晚期 NSCLC 患者发病率和死亡率的常见原因，常采用放射治疗（RT）进行治疗。在接受免疫检查点抑制剂（ICI）治疗的情况下，颅部 RT 的安全性尚未确定。
我们确定了 2013 年 8 月至 2016 年 9 月期间接受颅部 RT 治疗且接受或未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 合并脑转移患者。根据 ICI 治疗情况、颅部 RT 类型以及 ICI 与 RT 的时间关系，回顾性评估和分析 RT 相关不良事件（AE）。
在 163 例患者中，50 例（31%）接受了 ICI，113 例（69%）为 ICI 初治。总体而言，94 例（58%）、28 例（17%）和 101 例（62%）患者分别接受了立体定向放射外科手术、部分脑照射和/或全脑 RT。50%的患者接受了不止一次放疗。在不同的颅部 RT 类型中，ICI 初治和 ICI 治疗患者的所有分级 AE 发生率和 3 级或更高 AE 发生率均无显著差异（3 级或更高 AE 发生率在立体定向放射外科手术中分别为 ICI 初治患者的 8%和 ICI 治疗患者的 9%[p=1.00]，在全脑 RT 中分别为 ICI 初治患者的 8%和 ICI 治疗患者的 10%[p=0.71]）。此外，根据 ICI 与 RT 时间关系，AE 发生率也无差异。
ICI 治疗联合颅部 RT 并未导致 RT 相关 AE 显著增加，提示在接受颅部 RT 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。然而，仍需要更多的研究来验证这种方法。
