Clinical outcomes of melanoma brain metastases treated with stereotactic radiation and anti-PD-1 therapy
Clinical outcomes of melanoma brain metastases treated with stereotactic radiation and anti-PD-1 therapy
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立体定向放射联合抗PD-1治疗黑色素瘤脑转移瘤的临床结局
DOI：
10.1093/annonc/mdv622
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发表时间：
2016-03-01
影响因子：
50.5
通讯作者：
Gibney, G. T.
中科院分区：
文献类型：
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作者：
Ahmed, K. A.;Stallworth, D. G.;Gibney, G. T.
抗程序性死亡-1 （anti-PD-1）疗法nivolumab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治疗和立体定向放射治疗脑转移瘤（BMs）的患者的安全性和结果知之甚少。回顾性分析来自两个前瞻性纳武单抗方案的数据，该方案纳入了同一机构的160例晚期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个月内诊断出脑转移并接受立体定向放疗，则纳入患者。这项研究的主要终点是神经毒性；次要终点包括BM对照和生存。确定了26例患者，共73例脑转移治疗超过30个疗程。在纳武单抗治疗之前、期间和之后分别对33个病变（45%）、5个病变（7%）和35个病变（48%）进行放疗。除12例脑转移采用分步立体定向放射治疗外，所有脑转移均采用一次立体定向放射治疗（SRS），其中9例为术后治疗。1例患者在SRS后出现2级头痛，经类固醇治疗症状缓解。没有其他治疗相关的神经毒性或头皮反应的报道。注意到8例（11%）局部BM故障，每千分之一的体积增加20%。在这些病变中，4例出现出血，7例出现水肿。Kaplan-Meier估计放射后6个月和12个月局部脑脊髓炎控制率分别为91%和85%。在接受纳武单抗治疗未切除疾病的患者中，从立体定向放疗和纳武单抗开始治疗之日起的中位总生存期（OS）分别为11.8个月和12.0个月（OS中值未达到在切除环境中治疗的患者）。在我们的研究中，接受纳武单抗治疗的患者对立体定向放射治疗黑色素瘤脑转移具有良好的耐受性。与标准电流治疗相比，BM控制和OS延长。有必要进行前瞻性评价。
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 a parts per thousand yen20% 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.