Grant Krista-Gaie, Gillespie Yasmine, Karamian Armin, Lewin Isabella, Patel Shiv, Quigley Ashley, Lucke-Wold Brandon
University of Florida, College of Medicine, Gainesville, FL, United States.
University of Florida, College of Medicine, Gainesville, FL, United States.
Clin Neurol Neurosurg. 2025 Oct;257:109025. doi: 10.1016/j.clineuro.2025.109025. Epub 2025 Jun 26.
Melanoma brain metastases (MBM) affect up to 60 % of advanced melanoma cases and are associated with poor prognosis and significant neurologic morbidity. Recent advancements include immune checkpoint inhibitors (ICIs), BRAF/MEK-targeted inhibitors, stereotactic radiosurgery (SRS), and combination strategies, but optimal integration of these modalities remains unclear.
We conducted a systematic review of studies published from 2009 to 2024 across PubMed, Scopus, and Web of Science. Included studies reported outcomes such as overall survival (OS), progression-free survival (PFS), intracranial response rate (IRR), and adverse events (AEs) in patients receiving systemic therapies, radiotherapy, surgery, or combination regimens. Risk of bias was assessed using the Cochrane, Newcastle-Ottawa, and Joanna Briggs Institute (JBI) tools.
70 studies met inclusion criteria. ICIs demonstrated durable responses, especially in asymptomatic patients not requiring corticosteroids. Nivolumab and pembrolizumab offered superior response rates and OS versus chemotherapy. Targeted therapies like dabrafenib and vemurafenib produced rapid intracranial control but less durable responses. SRS improved local control with low neurotoxicity and showed synergy when combined with ICIs. Triple-modality strategies (surgery+SRS+systemic therapy) showed the most promising survival outcomes in selected patients. Median OS (mOS) ranged from 5.3 to 15.9 months, depending on treatment and patient selection.
Management of MBM is shifting toward multimodal approaches integrating local and systemic therapies. ICIs, particularly when paired with SRS, remain central to treatment. Prospective, biomarker-driven studies are needed to clarify treatment sequencing, maximize intracranial control, and improve quality of life (QoL).
黑色素瘤脑转移（MBM）影响高达60%的晚期黑色素瘤病例，与预后不良和显著的神经功能障碍相关。最近的进展包括免疫检查点抑制剂（ICI）、BRAF/MEK靶向抑制剂、立体定向放射外科（SRS）和联合策略，但这些治疗方式的最佳整合仍不明确。
我们对2009年至2024年在PubMed、Scopus和Web of Science上发表的研究进行了系统综述。纳入的研究报告了接受全身治疗、放疗、手术或联合治疗方案的患者的总生存期（OS）、无进展生存期（PFS）、颅内缓解率（IRR）和不良事件（AE）等结果。使用Cochrane、纽卡斯尔-渥太华和乔安娜·布里格斯研究所（JBI）工具评估偏倚风险。
70项研究符合纳入标准。ICI显示出持久的反应，尤其是在不需要使用皮质类固醇的无症状患者中。纳武单抗和帕博利珠单抗与化疗相比，具有更高的缓解率和总生存期。达拉非尼和维莫非尼等靶向治疗能快速实现颅内控制，但反应持续时间较短。SRS可改善局部控制，神经毒性低，与ICI联合使用时显示出协同作用。三联模式策略（手术+SRS+全身治疗）在特定患者中显示出最有前景的生存结果。根据治疗方法和患者选择，中位总生存期（mOS）为5.3至15.9个月。
MBM的管理正朝着整合局部和全身治疗的多模式方法转变。ICI，特别是与SRS联合使用时，仍然是治疗的核心。需要进行前瞻性的、基于生物标志物的研究，以明确治疗顺序，最大化颅内控制，并改善生活质量（QoL）。
