Ahmed K A, Stallworth D G, Kim Y, Johnstone P A S, Harrison L B, Caudell J J, Yu H H M, Etame A B, Weber J S, Gibney G T
Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa.
Department of Radiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa.
Ann Oncol. 2016 Mar;27(3):434-41. doi: 10.1093/annonc/mdv622. Epub 2015 Dec 27.
The anti-programmed death-1 (anti-PD-1) therapy nivolumab has significant clinical activity in patients with metastatic melanoma. However, little is known about the safety and outcomes in patients receiving anti-PD-1 therapy and stereotactic radiation for the treatment of brain metastases (BMs).
Data were analyzed retrospectively from two prospective nivolumab protocols enrolling 160 patients with advanced resected and unresectable melanoma at a single institution. Patients were included if BMs were diagnosed and treated with stereotactic radiation within 6 months of receiving nivolumab. The primary end point of this study was neurotoxicity; secondary end points included BM control and survival.
Twenty-six patients with a total of 73 BMs treated over 30 sessions were identified. Radiation was administered before, during and after nivolumab in 33 lesions (45%), 5 lesions (7%), and 35 lesions (48%), respectively. All BMs were treated with stereotactic radiosurgery (SRS) in a single session except 12 BMs treated with fractionated stereotactic radiation therapy, nine of which were in the postoperative setting. One patient experienced grade 2 headaches following SRS with symptomatic relief with steroid treatment. No other treatment-related neurologic toxicities or scalp reactions were reported. Eight (11%) local BM failures with a ≥20% increase in volume were noted. Of these lesions, hemorrhage was noted in 4, and edema was noted in 7. Kaplan-Meier estimates for local BM control following radiation at 6 and 12 months were 91% and 85%, respectively. Median overall survival (OS) from the date of stereotactic radiation and nivolumab initiation was 11.8 and 12.0 months, respectively, in patients receiving nivolumab for unresected disease (median OS was not reached in patients treated in the resected setting).
In our series, stereotactic radiation to melanoma BMs is well tolerated in patients who received nivolumab. BM control and OS appear prolonged compared with standard current treatment. Prospective evaluation is warranted.
抗程序性死亡-1（anti-PD-1）疗法纳武单抗在转移性黑色素瘤患者中具有显著的临床活性。然而，对于接受抗PD-1疗法和立体定向放射治疗脑转移瘤（BMs）的患者的安全性和预后知之甚少。
回顾性分析了两个前瞻性纳武单抗方案的数据，这两个方案纳入了一家机构的160例晚期可切除和不可切除黑色素瘤患者。如果在接受纳武单抗治疗的6个月内诊断出BMs并接受立体定向放射治疗，则将患者纳入研究。本研究的主要终点是神经毒性；次要终点包括BM控制和生存情况。
共确定了26例患者，其73个BMs接受了30次以上的治疗。放射治疗分别在纳武单抗治疗前、治疗期间和治疗后对33个病灶（45%）、5个病灶（7%）和35个病灶（48%）进行。除12个BMs接受分次立体定向放射治疗外，所有BMs均在单次治疗中接受立体定向放射外科（SRS）治疗，其中9个在术后进行。1例患者在SRS后出现2级头痛，经类固醇治疗后症状缓解。未报告其他与治疗相关的神经毒性或头皮反应。记录到8个（11%）局部BMs体积增加≥20%的失败病例。在这些病灶中，4个出现出血，7个出现水肿。放射治疗后6个月和12个月局部BM控制的Kaplan-Meier估计值分别为91%和85%。在接受纳武单抗治疗不可切除疾病的患者中，从立体定向放射治疗和开始使用纳武单抗之日起的中位总生存期（OS）分别为11.8个月和12.0个月（在接受切除治疗的患者中未达到中位OS）。
在我们的系列研究中，接受纳武单抗治疗的患者对黑色素瘤BMs进行立体定向放射治疗耐受性良好。与目前的标准治疗相比，BM控制和OS似乎有所延长。有必要进行前瞻性评估。
