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靶向 BRAF 和免疫检查点治疗时代黑素瘤脑转移患者的生存率提高。

Improved survival of patients with melanoma brain metastases in the era of targeted BRAF and immune checkpoint therapies.

机构信息

Department of General Surgery, Groningen University Medical Center, Groningen, The Netherlands.

Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, Florida.

出版信息

Cancer. 2018 Jan 15;124(2):297-305. doi: 10.1002/cncr.30946. Epub 2017 Oct 12.

Abstract

BACKGROUND

The development of brain metastases is common for systemic treatment failure in patients with melanoma and has been associated with a poor prognosis. Recent advances with BRAF and immune checkpoint therapies have led to improved patient survival. Herein, the authors evaluated the risk of de novo brain metastases and survival among patients with melanoma brain metastases (MBM) since the introduction of more effective therapies.

METHODS

Patients with unresectable AJCC stage III/IV melanoma who received first-line systemic therapy at Moffitt Cancer Center between 2000 and 2012 were identified. Data were collected regarding patient characteristics, stage of disease, systemic therapies, MBM status/management, and overall survival (OS). The risk of de novo MBM was calculated using a generalized estimating equation model and survival comparisons were performed using Kaplan-Meier and Cox proportional analyses.

RESULTS

A total of 610 patients were included, 243 of whom were diagnosed with MBM (40%). Patients with MBM were younger, with a lower frequency of regional metastasis. No significant differences were noted with regard to sex, BRAF status, or therapeutic class. The risk of de novo MBM was found to be similar among patients treated with chemotherapy, biochemotherapy, BRAF-targeted therapy, ipilimumab, and anti-programmed cell death protein 1/programmed death-ligand 1 regimens. The median OS of patients with MBM was significantly shorter when determined from the time of first regional/distant metastasis but not when determined from the time of first systemic therapy. The median OS from the time of MBM diagnosis was 7.5 months, 8.5 months, and 22.7 months, respectively, for patients diagnosed from 2000 to 2008, 2009 to 2010, and 2011 to the time of last follow-up (P = .002).

CONCLUSIONS

Brain metastases remain a common source of systemic treatment failure. The OS for patients with MBM has improved significantly. Further research into MBM prevention is needed. Cancer 2018;124:297-305. © 2017 American Cancer Society.

摘要

背景

黑色素瘤患者在全身治疗失败后常发生脑转移,且预后不良。近期 BRAF 和免疫检查点治疗的进展改善了患者的生存。本研究旨在评估自更有效的治疗方法问世以来,黑色素瘤脑转移(MBM)患者新发脑转移和生存的风险。

方法

收集 2000 年至 2012 年期间在莫菲特癌症中心接受一线全身治疗的不可切除的 AJCC 分期 III/IV 期黑色素瘤患者的数据。数据包括患者特征、疾病分期、全身治疗、MBM 情况/治疗和总生存(OS)。使用广义估计方程模型计算新发 MBM 的风险,并通过 Kaplan-Meier 和 Cox 比例分析进行生存比较。

结果

共纳入 610 例患者,其中 243 例诊断为 MBM(40%)。MBM 患者更年轻,局部转移频率更低。患者性别、BRAF 状态或治疗类型无显著差异。与接受化疗、生物化疗、BRAF 靶向治疗、伊匹单抗和抗程序性细胞死亡蛋白 1/程序性死亡配体 1 治疗的患者相比,新发 MBM 的风险无显著差异。从首次局部/远处转移时间确定的 MBM 患者 OS 明显短于从首次全身治疗时间确定的 OS。从 MBM 诊断时间开始,分别有 7.5、8.5 和 22.7 个月的中位 OS,诊断时间分别为 2000 年至 2008 年、2009 年至 2010 年和 2011 年至最后一次随访(P=0.002)。

结论

脑转移仍是全身治疗失败的常见原因。MBM 患者的 OS 显著改善。需要进一步研究 MBM 的预防。癌症 2018;124:297-305。© 2017 美国癌症协会。

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