Harvard Medical School, Boston, Massachusetts; Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts.
Harvard Medical School, Boston, Massachusetts; Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts.
Int J Radiat Oncol Biol Phys. 2018 Jul 1;101(3):624-629. doi: 10.1016/j.ijrobp.2018.02.175. Epub 2018 Mar 22.
Despite the emerging role of programmed cell death-1 (PD-1) pathway inhibitors for patients with advanced lung cancer, a paucity of data are available on the activity of these agents among patients with brain metastases. We investigated the outcomes of PD-1 pathway inhibitors and stereotactic radiosurgery (SRS) for the treatment of patients with brain metastases from lung cancer.
We retrospectively reviewed the medical records of non-small-cell lung cancer patients with brain metastases consecutively treated with PD-1 pathway inhibitors and SRS at our institution from 2012 to 2017. Overall survival (OS), distant brain failure (DBF), and local control (LC) were assessed using Kaplan-Meier estimates and Cox regression models.
We identified 37 patients treated with SRS to 85 lesions (90.6% intact and 9.4% resected) and a median total of 7 doses of PD-1 pathway inhibitors (83.8% nivolumab, 10.8% atezolizumab, 5.4% pembrolizumab). Most lesions were treated with 18 Gy in a single fraction (n = 61; 71.8%). Patients treated with concurrent SRS and PD-1 pathway inhibitors had longer OS and reduced rates of DBF compared with patients treated with SRS before or after PD-1 pathway inhibitor therapy (1-year OS, 87.3% vs 70.0% vs 0%, P = .008; 1-year DBF, 38.5% vs 65.8% vs 100%, P = .042). LC was favorable among lesions treated with SRS concurrent with or after PD-1 pathway inhibitor therapy compared with before PD-1 pathway inhibitor therapy (1-year LC, 100% vs 72.3%, P = .016). Three lesions transiently enlarged after SRS and then had partially or completely resolved on follow-up imaging. Four patients required steroids for SRS-associated toxicity. No patient experienced grade ≥ 4 toxicity.
Concurrent treatment with SRS and PD-1 pathway inhibitors was associated with favorable OS and locoregional disease control. This combination of therapy was well tolerated and merits further evaluation in larger cohorts in a prospective setting.
尽管程序性细胞死亡-1（PD-1）通路抑制剂在晚期肺癌患者中的作用日益凸显，但关于这些药物在脑转移患者中的疗效的数据却很少。我们研究了 PD-1 通路抑制剂联合立体定向放射外科（SRS）治疗肺癌脑转移患者的疗效。
我们回顾性分析了 2012 年至 2017 年在我院接受 PD-1 通路抑制剂联合 SRS 治疗的非小细胞肺癌脑转移患者的病历。采用 Kaplan-Meier 估计和 Cox 回归模型评估总生存期（OS）、远处脑失败（DBF）和局部控制（LC）。
我们共纳入 37 例患者，共 85 个病灶（90.6%为完整病灶，9.4%为切除病灶），中位 PD-1 通路抑制剂治疗剂量为 7 个周期（83.8%为纳武单抗，10.8%为阿特珠单抗，5.4%为派姆单抗）。大多数病灶接受单次 18Gy 照射（n=61；71.8%）。与 SRS 治疗后接受 PD-1 通路抑制剂治疗或 SRS 治疗前接受 PD-1 通路抑制剂治疗的患者相比，同期接受 SRS 和 PD-1 通路抑制剂治疗的患者 OS 更长，DBF 发生率更低（1 年 OS：87.3%比 70.0%比 0%，P=0.008；1 年 DBF：38.5%比 65.8%比 100%，P=0.042）。与 SRS 治疗前接受 PD-1 通路抑制剂治疗相比，同期或 SRS 治疗后接受 PD-1 通路抑制剂治疗的患者 LC 更有利（1 年 LC：100%比 72.3%，P=0.016）。3 个病灶在 SRS 后短暂增大，随后在随访影像学上部分或完全消退。4 例患者因 SRS 相关毒性需要使用类固醇。无患者发生≥4 级毒性。
同期 SRS 和 PD-1 通路抑制剂治疗与良好的 OS 和局部区域疾病控制相关。这种联合治疗方法耐受性良好，值得在更大的前瞻性队列中进一步评估。
