A pilot study of glioblastoma multiforme in elderly patients: Treatments, O-6-methylguanine-DNA methyltransferase (MGMT) methylation status and survival
A pilot study of glioblastoma multiforme in elderly patients: Treatments, O-6-methylguanine-DNA methyltransferase (MGMT) methylation status and survival
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DOI：
10.1016/j.clineuro.2012.12.023
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发表时间：
2013-08-01
影响因子：
1.9
通讯作者：
Iyer, V.
中科院分区：
文献类型：
--
作者：
Abhinav, K.;Aquilina, K.;Iyer, V.
目的：老年多形性胶质母细胞瘤（GBM）患者预后较差，接受的治疗方法也多种多样。 MGMT 基因启动子甲基化与 GBM 存活率的提高有关。我们检查了老年 GBM 患者的治疗方法和生存情况，包括与 MGMT 甲基化状态相关的情况。 患者和方法：包括在 2007 年 1 月 1 日至 2009 年 4 月 30 日之间诊断为 GBM 并接受活检、次全切除 (SIR) 或大体全切除 (GTR) 的≥ 65 岁患者。收集的信息包括 MGMT 状态 [甲基化 (ME) 与非甲基化 (UN)] 和生存数据。 p < 0.05 被认为是显着的。结果：59 名患者的诊断中位年龄为 72.68 岁 (65.72-85.04)。治疗包括手术（25 次 GTR、8 次 STR、26 次活检）、放化疗（22 次）和单纯放疗（20 次）。总体中位总生存期 (MOS) 为 219 天。放化疗的 MOS 为 316 天，而未放化疗的 MOS 为 143 天 (p = 0.011)。 47 名患者具有明确的 MGMT 状态（28 名 ME，19 名 UN）。在 ME 患者中，9/28 的患者接受了替莫唑胺治疗，而 UN 类别中这一比例为 10/19。具有明确 MGMT 状态的患者的替莫唑胺给药基于 WHO 体能状态 (p = 0.007)。 UN 组的 MOS 为 308 天，而 ME 组为 167 天 (p = 0.068)。在包括替莫唑胺使用、WHO 评分和甲基化状态的多变量 Cox 模型中，只有替莫唑胺的使用与死亡风险降低显着相关（HR 0.443，95% CI 0.200-0.982，p = 0.045）。结论：在这一小群患者中，适合老年 GBM 患者的放化疗似乎能带来生存获益。 MGMT 甲基化与生存率提高无关，替莫唑胺是导致生存率提高的唯一因素。无论该人群的 MGMT 状态如何，都应考虑使用替莫唑胺，未来需要进行大型前瞻性研究来进一步阐明这一点。 (C) 2013 Elsevier B.V. 保留所有权利。
Objectives: Elderly Glioblastoma multiforme (GBM) patients have a worse prognosis and receive variable treatments. MGMT gene promoter methylation is linked with improved survival in GBM. We examined treatments administered and survival including in relation to MGMT methylation status in elderly GBM patients.Patients and methods: Patients >= 65 years with diagnosed GBM between 1/01/2007 and 30/04/2009 and undergoing either a biopsy, subtotal (SIR) or gross total resection (GTR) were included. The collected information included MGMT status [methylated (ME) vs. unmethylated (UN)] and survival data. p < 0.05 was considered significant.Results: 59 patients were identified with median age at diagnosis being 72.68 years (65.72-85.04). Treatment included surgery (25 GTR, 8 STR, 26 biopsy), chemoradiation (22) and radiotherapy alone (20). Overall median overall survival (MOS) was 219 days. MOS with chemoradiation was 316 days vs. 143 days without it (p = 0.011). 47 patients had definite MGMT status (28 ME, 19 UN). In ME patients, 9/28 received temozolamide compared to 10/19 in UN category. Temozolamide administration in patients with definite MGMT status was based on WHO performance status (p = 0.007). MOS in UN group was 308 days vs. 167 days in ME group (p = 0.068). In a multivariate Cox model including use of temozolamide, WHO score and methylation status, only temozolamide use was significantly associated with a reduced risk for death (HR 0.443, 95% CI 0.200-0.982, p = 0.045).Conclusions: In this small cohort of patients, chemoradiation in suitable elderly GBM patients seemed to afford a survival benefit. MGMT methylation was not associated with an improved survival with temozolamide being the only factor leading to a better survival. Temozolamide use should be considered irrespective of MGMT status in this population with future large prospective studies needed to elucidate this further. (C) 2013 Elsevier B.V. All rights reserved.