Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins Hospital, Baltimore, Maryland.
Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins Hospital, Baltimore, Maryland; Johns Hopkins University School of Medicine, Baltimore, Maryland.
Int J Radiat Oncol Biol Phys. 2018 Mar 15;100(4):916-925. doi: 10.1016/j.ijrobp.2017.11.041. Epub 2017 Dec 5.
To characterize the effect of concurrent stereotactic radiosurgery-stereotactic radiation therapy (SRS-SRT) and immune checkpoint inhibitors on patient outcomes and safety in patients with brain metastases (BMs).
We retrospectively identified metastatic non-small cell lung cancer, melanoma, and renal cell carcinoma patients who had BMs treated with SRS-SRT from 2010 to 2016 without prior whole-brain radiation therapy. We included SRS-SRT patients who were treated with anti-cytotoxic T-lymphocyte-associated protein 4 (ipilimumab) and anti-programmed cell death protein 1 receptor (nivolumab, pembrolizumab). Patients who were given immune checkpoint inhibitors on active or unreported clinical trials were excluded, and concurrent immune checkpoint inhibition (ICI) was defined as ICI given within 2 weeks of SRS-SRT. Patients were managed with SRS-SRT, SRS-SRT with nonconcurrent ICI, or SRS-SRT with concurrent ICI. Progression-free survival and overall survival (OS) were estimated using Kaplan-Meier survival curves, and Cox proportional hazards models were used for multivariate analysis. Logistic regression was used to identify predictors of acute neurologic toxicity, immune-related adverse events, and new BMs.
A total of 260 patients were treated with SRS-SRT to 623 BMs. Of these patients, 181 were treated with SRS-SRT alone, whereas 79 received SRS-SRT and ICI, 35% of whom were treated with concurrent SRS-SRT and ICI. Concurrent ICI was not associated with increased rates of immune-related adverse events or acute neurologic toxicity and predicted for a decreased likelihood of the development of ≥3 new BMs after SRS-SRT (P=.045; odds ratio, 0.337). Median OS for patients treated with SRS-SRT, SRS-SRT with nonconcurrent ICI, and SRS-SRT with concurrent ICI was 12.9 months, 14.5 months, and 24.7 months, respectively. SRS-SRT with concurrent ICI was associated with improved OS compared with SRS-SRT alone (P=.002; hazard ratio [HR], 2.69) and compared with nonconcurrent SRS-SRT and ICI (P=.006; HR, 2.40) on multivariate analysis. The OS benefit of concurrent SRS-SRT and ICI was significant in comparison with patients treated with SRS-SRT before ICI (P=.002; HR, 3.82) or after ICI (P=.021; HR, 2.64).
Delivering SRS-SRT with concurrent ICI may be associated with a decreased incidence of new BMs and favorable survival outcomes without increased rates of adverse events.
研究立体定向放射外科-立体定向放射治疗（SRS-SRT）联合免疫检查点抑制剂对脑转移瘤（BMs）患者预后和安全性的影响。
我们回顾性分析了 2010 年至 2016 年间未接受全脑放疗的非小细胞肺癌、黑色素瘤和肾细胞癌脑转移患者的 SRS-SRT 治疗数据。我们纳入了接受抗细胞毒性 T 淋巴细胞相关蛋白 4（ipilimumab）和抗程序性细胞死亡蛋白 1 受体（nivolumab、pembrolizumab）治疗的 SRS-SRT 患者。排除了在活跃或未报告临床试验中接受免疫检查点抑制剂治疗的患者，同时将同期免疫检查点抑制（ICI）定义为 SRS-SRT 后 2 周内给予 ICI。患者接受 SRS-SRT、SRS-SRT 联合非同期 ICI 或 SRS-SRT 联合同期 ICI 治疗。采用 Kaplan-Meier 生存曲线估计无进展生存期和总生存期（OS），并采用 Cox 比例风险模型进行多变量分析。采用逻辑回归分析识别急性神经毒性、免疫相关不良事件和新发 BMs 的预测因素。
共 260 例患者接受 SRS-SRT 治疗 623 个 BMs。其中 181 例患者仅接受 SRS-SRT 治疗，79 例患者接受 SRS-SRT 联合 ICI 治疗，其中 35%的患者接受同期 SRS-SRT 联合 ICI 治疗。同期 ICI 并未增加免疫相关不良事件或急性神经毒性的发生率，反而降低了 SRS-SRT 后新发 BMs 数量≥3 的可能性（P=.045；比值比，0.337）。接受 SRS-SRT、SRS-SRT 联合非同期 ICI 和 SRS-SRT 联合同期 ICI 治疗的患者中位 OS 分别为 12.9 个月、14.5 个月和 24.7 个月。与单独接受 SRS-SRT 治疗相比，同期 SRS-SRT 联合 ICI 治疗（P=.002；风险比[HR]，2.69）和同期 SRS-SRT 联合非同期 ICI 治疗（P=.006；HR，2.40）均显著改善了 OS。与 SRS-SRT 治疗前（P=.002；HR，3.82）或 SRS-SRT 治疗后（P=.021；HR，2.64）接受 ICI 治疗的患者相比，同期 SRS-SRT 联合 ICI 治疗的 OS 获益更为显著。
SRS-SRT 联合同期 ICI 治疗可能会降低新发 BMs 的发生率并改善生存结局，而不会增加不良事件的发生率。
