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替莫唑胺放化疗辅助治疗老年胶质母细胞瘤患者 O6-甲基鸟嘌呤-DNA 甲基转移酶与生存的相关性。

Correlation between O6-methylguanine-DNA methyltransferase and survival in elderly patients with glioblastoma treated with radiotherapy plus concomitant and adjuvant temozolomide.

机构信息

Department of Radiation Oncology, Sant' Andrea Hospital, University La Sapienza, Via di Grottarossa 1035, 00189, Rome, Italy.

出版信息

J Neurooncol. 2011 Apr;102(2):311-6. doi: 10.1007/s11060-010-0324-4. Epub 2010 Aug 5.

Abstract

Epigenetic silencing of the O(6)-methylguanine-DNA-methyltransferase (MGMT) gene by promoter methylation is correlated with improved progression-free survival (PFS) and overall survival (OS) in adult patients with newly diagnosed glioblastoma multiforme (GBM) who receive alkylating agents. The aim of this study is to determine the correlation between MGMT and survival in elderly patients with GBM treated with radiotherapy (RT) and temozolomide (TMZ). Eighty-three patients aged 70 years or older with histologically confirmed GBM treated with RT plus TMZ between February 2005 and September 2009 were investigated in this study. The methylation status of the MGMT promoter was determined by polymerase chain reaction analysis. Median PFS and OS were 7.5 and 12.8 months, respectively. The MGMT promoter was methylated in 42 patients (50.6%) and unmethylated in 41 patients (49.4%). Median OS was 15.3 months in methylated patients and 10.2 months in unmethylated patients (P = 0.0001). Median PFS was 10.5 months in methylated tumors and 5.5 months in unmethylated tumors (P = 0.0001). On multivariate analysis MGMT methylation status emerged as the strongest independent prognostic factor for OS and PFS (P = 0.004 and P = 0.005, respectively). The results of the present study suggest that MGMT methylation status might be an important prognostic factor associated with better OS and PFS in elderly patients with GBM treated with RT and TMZ.

摘要

MGMT 基因启动子甲基化导致的表观遗传沉默与接受烷化剂治疗的新诊断多形性胶质母细胞瘤(GBM)成年患者的无进展生存期(PFS)和总生存期(OS)改善相关。本研究旨在确定接受放疗(RT)和替莫唑胺(TMZ)治疗的老年 GBM 患者中 MGMT 与生存之间的相关性。本研究调查了 2005 年 2 月至 2009 年 9 月期间接受 RT 联合 TMZ 治疗的 83 例年龄 70 岁或以上、组织学证实的 GBM 患者。通过聚合酶链反应分析确定 MGMT 启动子的甲基化状态。中位 PFS 和 OS 分别为 7.5 个月和 12.8 个月。MGMT 启动子在 42 例患者(50.6%)中发生甲基化,在 41 例患者(49.4%)中未发生甲基化。甲基化患者的中位 OS 为 15.3 个月,未甲基化患者的中位 OS 为 10.2 个月(P = 0.0001)。甲基化肿瘤的中位 PFS 为 10.5 个月,未甲基化肿瘤的中位 PFS 为 5.5 个月(P = 0.0001)。多变量分析显示,MGMT 甲基化状态是 OS 和 PFS 的最强独立预后因素(P = 0.004 和 P = 0.005)。本研究结果表明,MGMT 甲基化状态可能是接受 RT 和 TMZ 治疗的老年 GBM 患者 OS 和 PFS 较好的重要预后因素。

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