Acharya Sahaja, Mahmood Mustafaa, Mullen Daniel, Yang Deshan, Tsien Christina I, Huang Jiayi, Perkins Stephanie M, Rich Keith, Chicoine Michael, Leuthardt Eric, Dowling Joshua, Dunn Gavin, Keller Jesse, Robinson Clifford G, Abraham Christopher
Department of Radiation Oncology, Washington University, St. Louis, Missouri.
Department of Neurosurgery, Washington University, St. Louis, Missouri.
Adv Radiat Oncol. 2017 Aug 12;2(4):572-580. doi: 10.1016/j.adro.2017.07.003. eCollection 2017 Oct-Dec.
Stereotactic radiosurgery (SRS) in combination with immunotherapy (IMT) or targeted therapy is increasingly being used in the setting of melanoma brain metastases (MBMs). The synergistic properties of combination therapy are not well understood. We compared the distant intracranial failure rates of intact MBMs treated with SRS, SRS + IMT, and SRS + targeted therapy.
Combination therapy was defined as delivery of SRS within 3 months of IMT (anti-CTLA-4 /anti-PD-1 therapy) or targeted therapy (BRAF/MEK inhibitors). The primary endpoint was distant intracranial failure after SRS, which was defined as any new MBM identified on brain magnetic resonance imaging. Outcomes were evaluated using the Kaplan Meier method and Cox proportional hazards.
A total of 72 patients with melanoma with 233 MBMs were treated between April 2006 and April 2016. The number of MBMs within each treatment group was as follows: SRS: 121; SRS + IMT: 48; and SRS + targeted therapy: 64. The median follow-up was 8.9 months. One-year distant intracranial control rates for SRS, SRS + IMT, and SRS + targeted therapy were 11.5%, 60%, and 10%, respectively ( < .001). On multivariate analysis, after adjusting for steroid use and number of MBMs, SRS + IMT remained associated with a significant reduction in distant intracranial failure compared with SRS (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.29-0.80; = .003) and compared with SRS + targeted therapy (HR, 0.41; 95% CI, 0.25-0.68; = .001).One-year local control for SRS, SRS + IMT, and SRS + targeted therapy was 66%, 85%, and 72%, respectively ( = .044). On multivariate analysis, after adjusting for dose, SRS + IMT remained associated with a significant reduction in local failure compared with SRS alone (HR, 0.37; 95% CI, 0.14-0.95; = .04).
SRS with immunotherapy is associated with decreased distant and local intracranial failure compared with SRS alone. Prospective studies are warranted to validate this result.
立体定向放射外科（SRS）联合免疫疗法（IMT）或靶向疗法越来越多地用于黑色素瘤脑转移（MBM）的治疗。联合治疗的协同特性尚未得到充分了解。我们比较了接受SRS、SRS + IMT和SRS +靶向疗法治疗的完整MBM的远处颅内失败率。
联合治疗定义为在IMT（抗CTLA-4 /抗PD-1疗法）或靶向疗法（BRAF/MEK抑制剂）的3个月内进行SRS治疗。主要终点是SRS后的远处颅内失败，定义为脑磁共振成像上发现的任何新的MBM。使用Kaplan Meier方法和Cox比例风险模型评估结果。
2006年4月至2016年4月期间，共治疗了72例患有233个MBM的黑色素瘤患者。每个治疗组中的MBM数量如下：SRS：121个；SRS + IMT：48个；SRS +靶向疗法：64个。中位随访时间为8.9个月。SRS、SRS + IMT和SRS +靶向疗法的1年远处颅内控制率分别为11.5%、60%和10%（P <.001）。多变量分析显示，在调整类固醇使用和MBM数量后，与SRS相比，SRS + IMT与远处颅内失败的显著降低相关（风险比[HR]，0.48；95%置信区间[CI]，0.29 - 0.80；P =.003），与SRS +靶向疗法相比也相关（HR，0.41；95% CI，0.25 - 0.68；P =.001）。SRS、SRS + IMT和SRS +靶向疗法的1年局部控制率分别为66%、85%和72%（P =.044）。多变量分析显示，在调整剂量后，与单独的SRS相比，SRS + IMT与局部失败的显著降低相关（HR，0.37；95% CI，0.14 - 0.95；P =.04）。
与单独的SRS相比，SRS联合免疫疗法可降低远处和局部颅内失败率。需要进行前瞻性研究来验证这一结果。
