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MGMT启动子甲基化状态作为复发性胶质母细胞瘤伽玛刀放射外科治疗结果的预后因素。

MGMT promoter methylation status as a prognostic factor for the outcome of gamma knife radiosurgery for recurrent glioblastoma.

作者信息

Kim Byung Sup, Kong Doo-Sik, Seol Ho Jun, Nam Do-Hyun, Lee Jung-Il

机构信息

Department of Neurosurgery, Kosin University Gospel Hospital, Kosin University College of Medicine, Busan, 49267, Republic of Korea.

Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea.

出版信息

J Neurooncol. 2017 Jul;133(3):615-622. doi: 10.1007/s11060-017-2478-9. Epub 2017 May 23.

Abstract

We conducted this study to determine whether the methylation status of the O-methylguanine-DNA methyltransferase (MGMT) promoter was a prognostic marker for positive outcomes of gamma knife radiosurgery (GKS) for recurrent glioblastoma (GBM). We retrospectively examined 61 patients, who underwent GKS for local recurrent GBM between 2004 and 2015; in all patients, the methylation status of the MGMT promoter was identified via methylation-specific quantitative real-time polymerase chain reaction. All patients underwent surgical resection and were diagnosed histopathologically with GBM. Prognostic factors associated with progression-free survival (PFS) and overall survival (OS) were identified in univariate and multivariate analyses. Twenty-five (41%) had a methylated MGMT promoter, and 36 (59%) had an unmethylated MGMT promoter. The median age at GKS was 58 years. The median tumor volume at GKS was 7.0 cm, and the median marginal dose was 16 Gy. The median follow-up period after GKS was 7.5 months. The median PFS time after GKS was 8.9 months (95% CI 4.3-13.5 months) in the methylated and 4.6 months (95% CI 3.7-5.5 months) in the unmethylated group (P = 0.016). The median OS time after GKS was 14.0 months (95% CI 9.3-18.7 months) in the methylated group and 9.0 months (95% CI 6.5-11.5 months) in the unmethylated group (P = 0.026). Methylation of the MGMT promoter correlated with better PFS and OS after GKS for recurrent GBM. Prospective comparative studies are required to determine whether MGMT methylation directly affects the efficiency of GKS.

摘要

我们开展这项研究以确定O-甲基鸟嘌呤-DNA甲基转移酶(MGMT)启动子的甲基化状态是否为复发性胶质母细胞瘤(GBM)伽玛刀放射外科治疗(GKS)获得阳性结果的预后标志物。我们回顾性研究了2004年至2015年间因局部复发性GBM接受GKS治疗的61例患者;所有患者均通过甲基化特异性定量实时聚合酶链反应确定MGMT启动子的甲基化状态。所有患者均接受了手术切除,并经组织病理学诊断为GBM。在单因素和多因素分析中确定了与无进展生存期(PFS)和总生存期(OS)相关的预后因素。25例(41%)患者的MGMT启动子呈甲基化状态,36例(59%)患者的MGMT启动子呈非甲基化状态。接受GKS治疗时的中位年龄为58岁。接受GKS治疗时的中位肿瘤体积为7.0 cm,中位边缘剂量为16 Gy。GKS后的中位随访期为7.5个月。甲基化组GKS后的中位PFS时间为8.9个月(95%可信区间4.3 - 13.5个月),非甲基化组为4.6个月(95%可信区间3.7 - 5.5个月)(P = 0.016)。甲基化组GKS后的中位OS时间为14.0个月(95%可信区间9.3 - 18.7个月),非甲基化组为9.0个月(95%可信区间6.5 - 11.5个月)(P = 0.026)。复发性GBM患者GKS后,MGMT启动子甲基化与更好的PFS和OS相关。需要进行前瞻性比较研究以确定MGMT甲基化是否直接影响GKS的疗效。

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