Skin Cancer Center at the University Cancer Centre, Department of Dermatology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; National Center for Tumor Diseases (NCT), Dresden, and German Cancer Research Center (DKFZ), Heidelberg, Germany.
Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
Eur J Cancer. 2019 Mar;110:11-20. doi: 10.1016/j.ejca.2018.12.023. Epub 2019 Feb 7.
Combining stereotactic radiosurgery (SRS) and active systemic therapies (STs) achieved favourable survival outcomes in patients with melanoma brain metastases (MBMs) in retrospective analyses. However, several aspects of this treatment strategy remain poorly understood. We report on the overall survival (OS) of patients with MBM treated with a combination of radiotherapy (RT) and ST as well as the impact of the v-Raf murine sarcoma viral oncogene homolog B (BRAF)-V600 mutation (BRAFmut) status, types of RT and ST and their sequence.
Data of 208 patients treated with SRS or whole brain radiation therapy (WBRT) and either immunotherapy (IT) or targeted therapy (TT) within a 6-week interval to RT were analysed retrospectively. OS was calculated from RT to death or last follow-up. Univariate and multivariate Cox proportional hazard analyses were performed to determine prognostic features associated with OS.
The median follow-up was 7.3 months. 139 patients received IT, 67 received TT and 2 received IT and TT within 6 weeks to RT (WBRT 45%; SRS 55%). One-year Kaplan-Meier OS rates were 69%, 65%, 33% and 18% (P < .001) for SRS with IT, SRS with TT, WBRT with IT and WBRT with TT, respectively. Patients with a BRAFmut receiving IT combined with RT experienced higher OS rates (88%, 65%, 50% and 18%). TT following RT or started before and continued thereafter was associated with improved median OS compared with TT solely before RT (12.2 [95% confidence interval {CI} 9.3-15.1]; 9.8 [95% CI 6.9-12.6] versus 5.1 [95% CI 2.7-7.5]; P = .03).
SRS and IT achieved the highest OS rates. A BRAFmut appears to be a favourable prognostic factor for OS. For the combination of RT and TT, the sequence appears to be crucial. Combinations of WBRT and ST achieved unprecedentedly high OS rates and warrant further studies.
在回顾性分析中，立体定向放射外科（SRS）联合主动全身治疗（ST）为黑色素瘤脑转移（MBM）患者带来了有利的生存结果。然而，这种治疗策略的几个方面仍未被充分理解。我们报告了接受放疗（RT）联合 ST 治疗的 MBM 患者的总生存（OS）情况，以及 v-Raf 鼠肉瘤病毒致癌基因同源物 B（BRAF）-V600 突变（BRAFmut）状态、RT 类型、ST 类型及其顺序的影响。
回顾性分析了 208 例在 6 周内接受 SRS 或全脑放疗（WBRT），并在 RT 后接受免疫治疗（IT）或靶向治疗（TT）的患者的数据。OS 从 RT 至死亡或最后一次随访计算。采用单因素和多因素 Cox 比例风险分析确定与 OS 相关的预后因素。
中位随访时间为 7.3 个月。139 例患者接受 IT，67 例患者接受 TT，2 例患者在 RT 后 6 周内同时接受 IT 和 TT（WBRT45%；SRS55%）。SRS 联合 IT、SRS 联合 TT、WBRT 联合 IT 和 WBRT 联合 TT 的 1 年 Kaplan-Meier OS 率分别为 69%、65%、33%和 18%（P<.001）。接受 IT 联合 RT 治疗的 BRAFmut 患者的 OS 率更高（88%、65%、50%和 18%）。与 TT 仅在 RT 前使用相比，RT 后开始或在此之前开始并继续使用 TT 与中位 OS 延长相关（12.2[95%CI9.3-15.1]；9.8[95%CI6.9-12.6]比 5.1[95%CI2.7-7.5]；P=0.03）。
SRS 和 IT 实现了最高的 OS 率。BRAFmut 似乎是 OS 的有利预后因素。对于 RT 和 TT 的联合，顺序似乎是关键。WBRT 和 ST 的联合取得了前所未有的高 OS 率，值得进一步研究。
