接受抗 PD-1 治疗的转移性黑色素瘤患者中，治疗期间新发和原有脑转移的发生率、进展模式和结局。
Incidence, patterns of progression, and outcomes of preexisting and newly discovered brain metastases during treatment with anti-PD-1 in patients with metastatic melanoma.
机构信息
Department of Hematology/Oncology, Albert Einstein Israeli Hospital, Sao Paulo, Brazil.
Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
出版信息
Cancer. 2019 Dec 1;125(23):4193-4202. doi: 10.1002/cncr.32454. Epub 2019 Aug 9.
BACKGROUND
Melanoma brain metastases (MBM) occur in up to 50% of patients with metastatic melanoma (MM) and represent a frequent site of systemic treatment failure for targeted therapies. However, to the authors' knowledge, little is known regarding the incidence, patterns of disease progression, and outcomes of MBM in patients treated with anti-PD-1 immunotherapy.
METHODS
A total of 320 patients with MM who were treated with anti-PD-1 at The University of Texas MD Anderson Cancer Center in Houston were reviewed. Analyses were performed to identify factors associated with brain metastasis-free survival and overall survival (OS) using Cox regression models.
RESULTS
The median age of the patients was 63.3 years. OS from the initiation of anti-PD-1 therapy was not significantly different between patients without MBM prior to anti-PD-1 compared with patients with prior MBM (P = .359). Among patients without prior MBM, 21 patients (8.6%) developed MBM during anti-PD-1 therapy, 12 of whom (4.9%) presented with disease progression in the central nervous system (CNS) only. Developing MBM during or after therapy with anti-PD-1 (hazard ratio, 4.70; 95% CI, 3.18-6.93) was associated with shorter OS. Among patients with MBM prior to anti-PD-1 treatment, 15 (20.0%) progressed in the CNS only and 19 (25.3%) progressed both intracranially and extracranially; at the time of the last data cutoff, 27 patients (36.0%) had not developed disease progression. Radiation necrosis occurred in 11.3% of patients (7 of 62 patients) in the group with a prior MBM who received stereotactic radiosurgery.
CONCLUSIONS
Anti-PD-1 therapy may change the natural history of patients with preexisting MBM. However, CNS failure during treatment with anti-PD-1 is predictive of a worse prognosis compared with extracranial progression. The results of the current study support the activity of anti-PD-1 in patients with MBM, although routine CNS imaging during therapy is warranted.
背景
黑色素瘤脑转移（MBM）可发生于多达 50%的转移性黑色素瘤（MM）患者中，并且是针对靶向治疗的系统治疗失败的常见部位。然而，据作者所知，对于接受抗 PD-1 免疫治疗的患者，MBM 的发生率、疾病进展模式和结局知之甚少。
方法
对休斯顿德克萨斯大学 MD 安德森癌症中心接受抗 PD-1 治疗的 320 例 MM 患者进行了回顾性分析。使用 Cox 回归模型分析与脑转移无进展生存期和总生存期（OS）相关的因素。
结果
患者的中位年龄为 63.3 岁。从开始接受抗 PD-1 治疗起，与先前有 MBM 的患者相比，先前无 MBM 的患者的 OS 无显著差异（P=0.359）。在先前无 MBM 的患者中，有 21 例（8.6%）在接受抗 PD-1 治疗期间发生了 MBM，其中 12 例（4.9%）仅出现中枢神经系统（CNS）疾病进展。在接受抗 PD-1 治疗期间或之后发生 MBM（风险比，4.70；95%CI，3.18-6.93）与较短的 OS 相关。在先前接受抗 PD-1 治疗的 MBM 患者中，有 15 例（20.0%）仅出现 CNS 进展，19 例（25.3%）出现颅内和颅外同时进展；在最后一次数据截止时，27 例（36.0%）尚未出现疾病进展。先前有 MBM 并接受立体定向放射外科治疗的患者中，有 11.3%（7 例）出现放射性坏死。
结论
抗 PD-1 治疗可能改变先前存在 MBM 的患者的自然病史。然而，与颅外进展相比，在接受抗 PD-1 治疗期间发生 CNS 失败预示着预后更差。本研究的结果支持抗 PD-1 在 MBM 患者中的活性，尽管在治疗期间需要常规进行中枢神经系统成像。
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