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替莫唑胺联合干扰素-β治疗 MGMT 启动子未甲基化的新诊断原发性胶质母细胞瘤的疗效:一项多中心研究。

Benefits of interferon-β and temozolomide combination therapy for newly diagnosed primary glioblastoma with the unmethylated MGMT promoter: A multicenter study.

机构信息

Department of Neurosurgery, Nagoya University School of Medicine, Nagoya, Japan.

出版信息

Cancer. 2011 Apr 15;117(8):1721-30. doi: 10.1002/cncr.25637. Epub 2010 Nov 8.

DOI:10.1002/cncr.25637
PMID:21472719
Abstract

BACKGROUND

The aim of the current study was to catalog genomic and epigenomic abnormalities in newly diagnosed glioblastoma patients and determine the correlation among clinical, genetic, and epigenetic profiles and clinical outcome.

METHODS

This study retrospectively included 68 consecutive patients who underwent surgical treatment and received standard radiotherapy with temozolomide (TMZ)-based chemotherapy. Of a total of 68 patients, 39 patients (57.4%) received interferon (IFN)-β in combination of TMZ.

RESULTS

The genetic and epigenetic alterations frequently observed were EGFR amplification (51.5%), TP53 mutation (33.8%), CDKN2A loss (32.4%), TP53 loss (16.2%), methylation of the MGMT promoter (33.8%) and IDH1 mutation (5.9%). Multivariate analysis revealed that methylated MGMT promoter and the combination of TMZ and IFN-β were independent prognostic factors associated with survival. The median survival time (MST) of the patients who received the combination of IFN-β and TMZ was significantly greater with 19.9 months as compared to the TMZ alone group (12.7 months). Notably, in even patients whose tumors had unmethylated MGMT promoter, the MST prolonged to 17.2 months when receiving TMZ with IFN-β, compared to 12.5 months in those receiving TMZ without IFN-β.

CONCLUSIONS

Taken together, addition of IFN-β for newly diagnosed primary GBM achieved a favorable outcome, particularly in patients with unmethylated MGMT promoter.

摘要

背景

本研究旨在对新诊断的胶质母细胞瘤患者的基因组和表观基因组异常进行分类,并确定临床、遗传和表观遗传特征与临床结果之间的相关性。

方法

本研究回顾性纳入了 68 例接受手术治疗并接受标准放疗联合替莫唑胺(TMZ)化疗的连续患者。在总共 68 例患者中,有 39 例(57.4%)接受了 IFN-β联合 TMZ 治疗。

结果

经常观察到的遗传和表观遗传改变包括 EGFR 扩增(51.5%)、TP53 突变(33.8%)、CDKN2A 缺失(32.4%)、TP53 缺失(16.2%)、MGMT 启动子甲基化(33.8%)和 IDH1 突变(5.9%)。多变量分析显示,甲基化 MGMT 启动子和 TMZ 与 IFN-β联合治疗是与生存相关的独立预后因素。接受 IFN-β联合 TMZ 治疗的患者中位生存时间(MST)明显更长,为 19.9 个月,而仅接受 TMZ 治疗的患者 MST 为 12.7 个月。值得注意的是,即使患者肿瘤的 MGMT 启动子未甲基化,当接受 TMZ 联合 IFN-β治疗时,MST 也延长至 17.2 个月,而单独接受 TMZ 治疗时 MST 为 12.5 个月。

结论

总的来说,新诊断的原发性 GBM 患者加用 IFN-β可获得较好的结果,尤其是 MGMT 启动子未甲基化的患者。

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