Nardin Charlee, Mateus Christine, Texier Mathieu, Lanoy Emilie, Hibat-Allah Salima, Ammari Samy, Robert Caroline, Dhermain Frederic
Departments of Dermatology.
Biostastistics and Epidemiology.
Melanoma Res. 2018 Apr;28(2):111-119. doi: 10.1097/CMR.0000000000000413.
Anti-programmed cell death-1 (anti-PD1) antibodies are currently the first-line treatment for patients with metastatic BRAF wild-type melanoma, alone or combined with the anti-CTLA4 monoclonal antibody, ipilimumab. To date, data on safety and the outcomes of patients treated with the anti-PD1 monoclonal antibodies, pembrolizumab (PB), or nivolumab, combined with stereotactic radiosurgery (SRS), for melanoma brain metastases (MBM) are scarce. We retrospectively reviewed all patients with MBM treated with PB combined with SRS between 2012 and 2015. The primary endpoint was neurotoxicity. The secondary endpoints were local, distant intracranial controls and overall survival (OS). Among 74 patients with MBM treated with SRS, 25 patients with a total of 58 MBM treated with PB combined with SRS within 6 months were included. Radiation necrosis, occurring within a median time of 6.5 months, was observed for four MBM (6.8%) in four patients. No other significant SRS-related adverse event was observed. After a median follow-up of 8.4 months, local control was achieved in 46 (80%) metastases and 17 (68%) patients. Perilesional oedema and intratumour haemorrhage appearing or increasing after SRS were associated with local progression (P<0.001). The median OS was 15.3 months (95% confidence interval: 4.6-26). The timing between SRS and PB administration did not seem to influence the risk of radiation necrosis, intracranial control or OS. SRS combined with PB was well tolerated and achieved local control in 80% of the lesions. Prolonged OS was observed compared with that currently yielded in this population of patients. Prospective studies are required to explore further the optimal ways to combine immunotherapy and SRS.
抗程序性细胞死亡蛋白1（抗PD1）抗体目前是转移性BRAF野生型黑色素瘤患者的一线治疗药物，可单独使用或与抗CTLA4单克隆抗体伊匹单抗联合使用。迄今为止，关于抗PD1单克隆抗体帕博利珠单抗（PB）或纳武单抗联合立体定向放射外科（SRS）治疗黑色素瘤脑转移（MBM）患者的安全性和疗效数据很少。我们回顾性分析了2012年至2015年间接受PB联合SRS治疗的所有MBM患者。主要终点是神经毒性。次要终点是局部、远处颅内控制和总生存期（OS）。在74例接受SRS治疗的MBM患者中，纳入了25例在6个月内接受PB联合SRS治疗的共58个MBM患者。4例患者的4个MBM（6.8%）出现了放射性坏死，中位发生时间为6.5个月。未观察到其他与SRS相关的显著不良事件。中位随访8.4个月后，46个（80%）转移灶和17例（68%）患者实现了局部控制。SRS后出现或加重的瘤周水肿和肿瘤内出血与局部进展相关（P<0.001）。中位OS为15.3个月（95%置信区间：4.6 - 26）。SRS与PB给药之间的时间间隔似乎不影响放射性坏死、颅内控制或OS的风险。SRS联合PB耐受性良好，80%的病灶实现了局部控制。与该患者群体目前的生存期相比，观察到生存期延长。需要进行前瞻性研究以进一步探索免疫治疗与SRS联合的最佳方式。
