Department of Neurosurgery and Brain Metastasis Center, Memorial Sloan Kettering Cancer Center, New York, New York.
Department of Neurosurgery, New York Presbyterian Hospital/Weill Cornell Medical College, New York, New York.
Cancer. 2021 Jun 15;127(12):2062-2073. doi: 10.1002/cncr.33459. Epub 2021 Mar 2.
Historically, the prognosis for patients who have melanoma brain metastasis (MBM) has been dismal. However, breakthroughs in targeted and immunotherapies have improved long-term survival in those with advanced melanoma. Therefore, MBM presentation, prognosis, and the use of multimodality central nervous system (CNS)-directed treatment were reassessed.
In this retrospective study, the authors evaluated patients with MBM who received treatment at Memorial Sloan Kettering Cancer Center between 2010 and 2019. Kaplan-Meier methodology was used to describe overall survival (OS). Recursive partitioning analysis and time-dependent multivariable Cox modeling were used to assess prognostic variables and to associate CNS-directed treatments with OS.
Four hundred twenty-five patients with 2488 brain metastases were included. The median OS after an MBM diagnosis was 8.9 months (95% CI, 7.9-11.3 months). Patients who were diagnosed with MBM between 2015 and 2019 experienced longer OS compared to those who were diagnosed between 2010 and 2014 (OS, 13.0 months [95% CI, 10.47-17.06 months] vs 7.0 months [95% CI, 6.1-8.3 months]; P = .0003). Prognostic multivariable modeling significantly associated shortened OS independently with leptomeningeal dissemination (P < .0001), increasing numbers of brain metastases at diagnosis (P < .0001), earlier MBM diagnosis year (P = .0008), higher serum levels of lactate dehydrogenase (P < .0001), receipt of immunotherapy before MBM diagnosis (P = .003), and the presence of extracranial disease (P = .02). The use of different CNS-directed treatment modalities was associated with presenting symptoms, diagnosis year, number and size of brain metastases, and the presence of extracranial disease. Multivariable analysis demonstrated improved survival for patients who underwent craniotomy (P = .01).
The prognosis for patients with MBM has improved within the last 5 years, coinciding with the approval of PD-1 immune checkpoint blockade and combined BRAF/MEK targeting. Improving survival reflects and may influence the willingness to use aggressive multimodality treatment for MBM.
Historically, melanoma brain metastases (MBM) have carried a poor survival prognosis of 4 to 6 months; however, the introduction of immunotherapy and targeted precision medicines has altered the survival curve for advanced melanoma. In this large, single-institution, contemporary cohort, the authors demonstrate a significant increase in survival of patients with MBM to 13 months within the last 5 years of the study. A worse prognosis for patients with MBM was significantly associated with the number of metastases at diagnosis, previous exposure to immunotherapy, spread of disease to the leptomeningeal compartment, serum lactate dehydrogenase elevation, and the presence of extracranial disease. The current age of systemic treatments has also been accompanied by shifts in the use of central nervous system-directed therapies.
历史上，患有黑色素瘤脑转移（MBM）的患者预后一直很差。然而，靶向和免疫疗法的突破改善了晚期黑色素瘤患者的长期生存。因此，重新评估了 MBM 的表现、预后以及多模式中枢神经系统（CNS）定向治疗的应用。
在这项回顾性研究中，作者评估了 2010 年至 2019 年期间在 Memorial Sloan Kettering Cancer Center 接受治疗的 MBM 患者。Kaplan-Meier 方法用于描述总生存期（OS）。递归分区分析和时间相关多变量 Cox 建模用于评估预后变量，并将 CNS 定向治疗与 OS 相关联。
共纳入 425 例有 2488 个脑转移瘤的患者。MBM 诊断后的中位 OS 为 8.9 个月（95%CI，7.9-11.3 个月）。2015 年至 2019 年诊断为 MBM 的患者的 OS 长于 2010 年至 2014 年诊断为 MBM 的患者（OS，13.0 个月[95%CI，10.47-17.06 个月] vs. 7.0 个月[95%CI，6.1-8.3 个月]；P =.0003）。预后多变量建模显著独立地与脑膜播散（P <.0001）、诊断时脑转移瘤数量增加（P <.0001）、MBM 诊断年份较早（P =.0008）、血清乳酸脱氢酶水平升高（P <.0001）、MBM 诊断前接受免疫治疗（P =.003）和存在颅外疾病（P =.02）有关。不同 CNS 定向治疗方式的使用与首发症状、诊断年份、脑转移瘤的数量和大小以及存在颅外疾病有关。多变量分析显示接受手术切除术的患者生存率提高（P =.01）。
在过去 5 年中，MBM 患者的预后有所改善，这与 PD-1 免疫检查点阻断和联合 BRAF/MEK 靶向治疗的批准相符。生存率的提高反映并可能影响对 MBM 采用积极的多模式治疗的意愿。
黑色素瘤脑转移（MBM）患者的历史预后为 4 至 6 个月；然而，免疫疗法和靶向精准药物的出现改变了晚期黑色素瘤的生存曲线。在这项大型的单机构当代队列研究中，作者证明了 MBM 患者的生存显著改善，在研究的最后 5 年内达到 13 个月。MBM 患者预后较差与诊断时转移瘤的数量、先前暴露于免疫治疗、疾病向脑膜扩散、血清乳酸脱氢酶升高和存在颅外疾病显著相关。目前的全身治疗时代也伴随着中枢神经系统定向治疗应用的转变。
