Concurrent Immune Checkpoint Inhibitors and Stereotactic Radiosurgery for Brain Metastases in Non-Small Cell Lung Cancer, Melanoma, and Renal Cell Carcinoma
Concurrent Immune Checkpoint Inhibitors and Stereotactic Radiosurgery for Brain Metastases in Non-Small Cell Lung Cancer, Melanoma, and Renal Cell Carcinoma
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非小细胞肺癌、黑色素瘤和肾细胞癌脑转移的同步免疫检查点抑制剂和立体定向放射外科治疗
DOI：
10.1016/j.ijrobp.2017.11.041
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发表时间：
2018-03-15
影响因子：
7
通讯作者：
Redmond, Kristin J.
中科院分区：
文献类型：
--
作者：
Chen, Linda;Douglass, Jacqueline;Redmond, Kristin J.
目的：探讨同步立体定向放射外科-立体定向放射治疗 (SRS-SRT) 和免疫检查点抑制剂对脑转移瘤 (BM) 患者预后和安全性的影响。方法和材料：我们回顾性鉴定了 2010 年至 2016 年接受 SRS-SRT 治疗但未接受全脑放射治疗的转移性非小细胞肺癌、黑色素瘤和肾细胞癌患者。我们纳入了接受抗细胞毒性 T 淋巴细胞相关蛋白 4（伊匹单抗）和抗程序性细胞死亡蛋白 1 受体（纳武单抗、派姆单抗）治疗的 SRS-SRT 患者。在活跃或未报告的临床试验中接受免疫检查点抑制剂的患者被排除在外，并发免疫检查点抑制（ICI）被定义为SRS-SRT 2周内给予的ICI。患者接受 SRS-SRT、非并发 ICI 的 SRS-SRT 或并发 ICI 的 SRS-SRT 治疗。使用Kaplan-Meier生存曲线估计无进展生存期和总生存期（OS），并使用Cox比例风险模型进行多变量分析。使用 Logistic 回归来确定急性神经毒性、免疫相关不良事件和新 BM 的预测因子。结果：共有 260 名患者接受了 623 例 BM 的 SRS-SRT 治疗。在这些患者中，181 例仅接受 SRS-SRT 治疗，79 例接受 SRS-SRT 和 ICI 治疗，其中 35% 接受 SRS-SRT 和 ICI 同步治疗。并发 ICI 与免疫相关不良事件或急性神经毒性发生率增加无关，并预测 SRS-SRT 后出现 >= 3 个新 BM 的可能性降低（P=.045；比值比，0.337）。接受 SRS-SRT、非并发 ICI 的 SRS-SRT 和并发 ICI 的 SRS-SRT 治疗的患者的中位 OS 分别为 12.9 个月、14.5 个月和 24.7 个月。在多变量分析中，与单独 SRS-SRT 相比（P=.002；风险比 [HR]，2.69）以及与非同时 SRS-SRT 和 ICI 相比（P=.006；HR，2.40），SRS-SRT 联合 ICI 与 OS 改善相关。与 ICI 前（P=0.002；HR，3.82）或 ICI 后（P=0.021；HR，2.64）接受 SRS-SRT 治疗的患者相比，同步 SRS-SRT 和 ICI 的 OS 获益显着。结论：同时 ICI 时提供 SRS-SRT 可能与新 BM 发生率降低和有利的生存结果相关，且不良事件发生率不增加。 (C) 2017 Elsevier Inc. 保留所有权利。
Purpose: 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).Methods and Materials: 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.Results: 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).Conclusions: 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. (C) 2017 Elsevier Inc. All rights reserved.