Shepard Matthew J, Xu Zhiyuan, Donahue Joseph, Eluvathingal Muttikkal Thomas J, Cordeiro Diogo, Hansen Leslie, Mohammed Nasser, Gentzler Ryan D, Larner James, Fadul Camilo E, Sheehan Jason P
Departments of1Neurological Surgery.
2Neuroradiology.
J Neurosurg. 2019 Jul 26;133(3):685-692. doi: 10.3171/2019.4.JNS19822. Print 2020 Sep 1.
Immune checkpoint inhibitors (ICIs) improve survival in patients with advanced non-small cell lung cancer (NSCLC). Clinical trials examining the efficacy of ICIs in patients with NSCLC excluded patients with untreated brain metastases (BMs). As stereotactic radiosurgery (SRS) is commonly employed for NSCLC-BMs, the authors sought to define the safety and radiological and clinical outcomes for patients with NSCLC-BMs treated with concurrent ICI and SRS.
A retrospective matched cohort study was performed on patients who had undergone SRS for one or more NSCLC-derived BMs. Two matched cohorts were identified: one that received ICI before or after SRS within a 3-month period (concurrent ICI) and one that did not (ICI naive). Locoregional tumor control, peritumoral edema, and central nervous system (CNS) adverse events were compared between the two cohorts.
Seventeen patients (45 BMs) and 34 patients (92 BMs) composed the concurrent-ICI and ICI-naive cohorts, respectively. There was no statistically significant difference in overall survival (HR 0.99, 95% CI 0.39-2.52, p = 0.99) or CNS progression-free survival (HR 2.18, 95% CI 0.72-6.62, p = 0.11) between the two groups. Similarly, the 12-month local tumor control rate was 84.9% for tumors in the concurrent-ICI cohort versus 76.3% for tumors in the ICI-naive cohort (p = 0.94). Further analysis did reveal that patients receiving concurrent ICI had increased rates of CNS complete response for BMs treated with SRS (8/16 [50%] vs 5/32 [15.6%], p = 0.012) per the Response Assessment in Neuro-Oncology (RANO) criteria. There was also a shorter median time to BM regression in the concurrent-ICI cohort (2.5 vs 3.1 months, p < 0.0001). There was no increased rate of radiation necrosis or intratumoral hemorrhage in the patients receiving concurrent ICI (5.9% vs 2.9% in ICI-naive cohort, p = 0.99). There was no significant difference in the rate of peritumoral edema progression between the two groups (concurrent ICI: 11.1%, ICI naive: 21.7%, p = 0.162).
The concurrent use of ICI and SRS to treat NSCLC-BM was well tolerated while providing more rapid BM regression. Concurrent ICI did not increase peritumoral edema or rates of radiation necrosis. Further studies are needed to evaluate whether combined ICI and SRS improves progression-free survival and overall survival for patients with metastatic NSCLC.
免疫检查点抑制剂（ICI）可提高晚期非小细胞肺癌（NSCLC）患者的生存率。在NSCLC患者中检验ICI疗效的临床试验排除了未经治疗的脑转移（BM）患者。由于立体定向放射外科（SRS）常用于NSCLC脑转移瘤，作者试图明确接受ICI与SRS联合治疗的NSCLC脑转移瘤患者的安全性、放射学及临床结局。
对因一个或多个源自NSCLC的脑转移瘤接受SRS治疗的患者进行回顾性匹配队列研究。确定了两个匹配队列：一个在3个月内于SRS之前或之后接受ICI治疗（ICI联合治疗组），另一个未接受ICI治疗（单纯ICI组）。比较两组的局部肿瘤控制、瘤周水肿及中枢神经系统（CNS）不良事件。
ICI联合治疗组有17例患者（45个脑转移瘤），单纯ICI组有34例患者（92个脑转移瘤）。两组的总生存期（风险比[HR]0.99，95%置信区间[CI]0.39 - 2.52，p = 0.99）或CNS无进展生存期（HR 2.18，95% CI 0.72 - 6.62，p = 0.11）无统计学显著差异。同样，ICI联合治疗组肿瘤的12个月局部肿瘤控制率为84.9%，单纯ICI组肿瘤为76.3%（p = 0.94）。进一步分析确实显示，根据神经肿瘤学疗效评估（RANO）标准，接受ICI联合治疗的患者经SRS治疗的脑转移瘤的CNS完全缓解率更高（8/16 [50%] 对5/32 [15.6%]，p = 0.012）。ICI联合治疗组脑转移瘤消退的中位时间也更短（2.5个月对3.1个月，p < 0.0001）。接受ICI联合治疗的患者放射性坏死或瘤内出血发生率未增加（5.9%对单纯ICI组的2.9%，p = 0.99）。两组瘤周水肿进展率无显著差异（ICI联合治疗组：11.1%，单纯ICI组：21.7%，p = 0.162）。
ICI与SRS联合用于治疗NSCLC脑转移瘤耐受性良好，同时能使脑转移瘤更快消退。ICI联合治疗未增加瘤周水肿或放射性坏死发生率。需要进一步研究评估ICI与SRS联合应用是否能改善转移性NSCLC患者的无进展生存期和总生存期。
