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BRAF抑制剂与立体定向放射外科联合治疗对黑色素瘤脑转移患者总生存期的影响。

Impact on overall survival of the combination of BRAF inhibitors and stereotactic radiosurgery in patients with melanoma brain metastases.

作者信息

Wolf Amparo, Zia Sayyad, Verma Rashika, Pavlick Anna, Wilson Melissa, Golfinos John G, Silverman Joshua S, Kondziolka Douglas

机构信息

Departments of Neurosurgery, Laura and Isaac Perlmutter Cancer Center, NYU Langone Medical Center, New York University, Suite 8R, 530 First Avenue, New York, NY, 10016, USA.

Medical Oncology, Laura and Isaac Perlmutter Cancer Center, NYU Langone Medical Center, New York University, New York, NY, USA.

出版信息

J Neurooncol. 2016 May;127(3):607-15. doi: 10.1007/s11060-016-2072-6. Epub 2016 Feb 6.

Abstract

The aim of this study was to evaluate the impact of BRAF inhibitors on survival outcomes in patients receiving stereotactic radiosurgery (SRS) for melanoma brain metastases. We prospectively collected treatment parameters and outcomes for 80 patients with melanoma brain metastases who underwent SRS. Thirty-five patients harbored the BRAF mutation (BRAF-M) and 45 patients did not (BRAF-WT). Univariate and multivariate analyses were performed to identify predictors of overall survival. The median overall survival from first SRS procedure was 6.7, 11.2 months if treated with a BRAF inhibitor and 4.5 months for BRAF-WT. Actuarial survival rates for BRAF-M patients on an inhibitor were 54 % at 6 months and 41 % at 12 months from the time of SRS. In contrast, BRAF-WT had overall survival rates of 28 % at 6 months and 19 % at 12 months. Overall survival was extended for patients on a BRAF inhibitor at or after the first SRS. The median time to intracranial progression was 3.9 months on a BRAF inhibitor and 1.7 months without. The local control rate for all treated tumors was 92.5 %, with no difference based on BRAF status. Patients with higher KPS, fewer treated intracranial metastases, controlled systemic disease, RPA Class 1 and BRAF-M patients had extended overall survival. Overall, patients with BRAF-M treated with both SRS and BRAF inhibitors, at or after SRS, have increased overall survival from the time of SRS. As patients live longer as a result of more effective systemic and local therapies, close surveillance and early management of intracranial disease with SRS will become increasingly important.

摘要

本研究的目的是评估BRAF抑制剂对接受立体定向放射外科治疗(SRS)的黑色素瘤脑转移患者生存结局的影响。我们前瞻性收集了80例接受SRS治疗的黑色素瘤脑转移患者的治疗参数和结局。35例患者存在BRAF突变(BRAF-M),45例患者不存在BRAF突变(BRAF-WT)。进行单因素和多因素分析以确定总生存的预测因素。首次SRS手术后的中位总生存期为6.7个月,接受BRAF抑制剂治疗的患者为11.2个月,BRAF-WT患者为4.5个月。从SRS时起,接受抑制剂治疗的BRAF-M患者6个月时的精算生存率为54%,12个月时为41%。相比之下,BRAF-WT患者6个月时的总生存率为28%,12个月时为19%。首次SRS时或之后接受BRAF抑制剂治疗的患者总生存期延长。使用BRAF抑制剂时颅内进展的中位时间为3.9个月,未使用时为1.7个月。所有治疗肿瘤的局部控制率为92.5%,基于BRAF状态无差异。KPS较高、治疗的颅内转移灶较少、全身疾病得到控制、RPA 1级以及BRAF-M患者的总生存期延长。总体而言,接受SRS和BRAF抑制剂治疗的BRAF-M患者在SRS时或之后总生存期从SRS时起有所增加。由于更有效的全身和局部治疗使患者寿命延长,通过SRS对颅内疾病进行密切监测和早期管理将变得越来越重要。

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