在通过放射外科对脑转移瘤进行系统性前期控制后接受靶向治疗和免疫治疗的黑色素瘤患者的生存率。

Survival of melanoma patients treated with targeted therapy and immunotherapy after systematic upfront control of brain metastases by radiosurgery.

作者信息

Gaudy-Marqueste C, Dussouil A S, Carron R, Troin L, Malissen N, Loundou A, Monestier S, Mallet S, Richard M A, Régis J M, Grob J J

机构信息

Dermatology and Skin Cancers Department, UMR911 CRO2, Aix-Marseille University, APHM, Marseille, France.

Department of Stereotaxic and Functional Neurosurgery, Gamma-knife Unit, Inserm U751, Aix-Marseille University, APHM, Marseille, France.

出版信息

Eur J Cancer. 2017 Oct;84:44-54. doi: 10.1016/j.ejca.2017.07.017. Epub 2017 Aug 4.

DOI:10.1016/j.ejca.2017.07.017

PMID:28783540

Abstract

BACKGROUND

Targeted therapy (TT) and immunotherapies (ITs) have dramatically improved survival in metastatic melanoma (MM). However, their efficacy on brain metastasis (BM) remains limited and poorly documented.

PATIENTS AND METHODS

Retrospective cohort of consecutive MM patients (pts) with BMs, all systematically upfront treated by Gamma-Knife (GK) at first BM and retreated in case of new BMs, from 2010 to 2015 at the time when ipilimumab BRAF ± MEK inhibitors and anti-PD1 were introduced in practice. Survival after 1st GK (OS) according to prognostic factors and treatment.

RESULTS

Among 179 consecutive pts treated by GK, 109 received IT and/or TT after the 1st GK. Median OS was 10.95 months and 1- and 2-year survival rates were 49.5% and 27.4%, respectively, versus a median overall survival (OS) of 2.29 months (p < .001) in those who did not receive IT or TT. In pts who initially had a single BM, median OS and 1- and 2-year survival rates were 14.46 months, 66.7% and 43.4%, respectively; in pts with 2-3 BMs: 8.85 months, 46.4% and 31%, respectively; in pts with >3 BMs: 7.25 months, 37.2% and 11.9%, respectively. Multivariate analysis for OS confirmed that IT and TT were significantly and highly protective. Best OS was observed in BRAF-wild-type pts receiving anti-PD1 or in BRAF-mutated pts receiving BRAF-inhibitors and anti-PD1 (12.26 and 14.82 months, respectively).

CONCLUSION

In real-life MM pts with BMs, a strategy aiming at controlling BM with GK together with TT and/or TT seems to achieve unprecedented survival rates.

摘要

背景

靶向治疗（TT）和免疫疗法（IT）显著提高了转移性黑色素瘤（MM）患者的生存率。然而，它们对脑转移（BM）的疗效仍然有限，且相关记录较少。

患者与方法

对2010年至2015年期间连续的MM合并BM患者进行回顾性队列研究，所有患者在首次发生BM时均接受伽玛刀（GK）系统的一线治疗，若出现新的BM则进行再次治疗，当时伊匹单抗、BRAF±MEK抑制剂和抗PD1已在临床应用。根据预后因素和治疗情况分析首次GK治疗后的生存率（OS）。

结果

在179例接受GK治疗的连续患者中，109例在首次GK治疗后接受了IT和/或TT。中位OS为10.95个月，1年和2年生存率分别为49.5%和27.4%，而未接受IT或TT的患者中位总生存期（OS）为2.29个月（p <.001）。最初仅有单个BM的患者，中位OS和1年、2年生存率分别为14.46个月、66.7%和43.4%；有2 - 3个BM的患者分别为8.85个月、46.4%和31%；有超过3个BM的患者分别为7.25个月、37.2%和11.9%。OS的多因素分析证实，IT和TT具有显著且高度的保护作用。在接受抗PD1的BRAF野生型患者或接受BRAF抑制剂和抗PD1的BRAF突变型患者中观察到最佳OS（分别为12.26个月和14.82个月）。