MGMT Gene Promoter Methylation as a Potent Prognostic Factor in Glioblastoma Treated With Temozolomide-Based Chemoradiotherapy: A Single-Institution Study
MGMT Gene Promoter Methylation as a Potent Prognostic Factor in Glioblastoma Treated With Temozolomide-Based Chemoradiotherapy: A Single-Institution Study
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DOI：
10.1016/j.ijrobp.2011.12.086
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发表时间：
2012-11-01
影响因子：
7
通讯作者：
Suh, Chang-Ok
中科院分区：
文献类型：
--
作者：
Kim, Young Suk;Kim, Se Hoon;Suh, Chang-Ok
目的：近年来发现O-6-甲基鸟嘌呤-DNA甲基转移酶（MGMT）缺陷的细胞对替莫唑胺（TMZ）的敏感性增加。我们评估MGMT的高甲基化是否与多形性胶质母细胞瘤（GBM）患者的生存率相关。方法和材料：我们回顾性分析了2001年至2008年接受TMZ累及野放疗的93例经组织学证实的GBM患者。中位年龄为58岁（范围：24-78岁）。39例患者（42%）全部手术切除，30例患者（32%）次全切除，17例患者（18%）部分切除; 7例患者（8%）仅进行了活检。87%的患者在手术后3周内开始术后放疗。放射治疗剂量范围为50至74戈伊（中位数，70戈伊）。在78例患者中测定了MGMT基因甲基化; 43例患者（55%）MGMT未甲基化，35例患者（45%）甲基化。结果：中位总生存期（OS）为22个月，无进展生存期（PFS）为11个月。在多变量分析中，MGMT基因甲基化是OS（p = 0.002）和PFS（p = 0.008）的独立显著预后因素。甲基化组的中位OS为29个月，未甲基化组的中位OS为20个月。在35例MGMT基因甲基化患者中，2年和5年OS率分别为54%和31%。6例合并MGMT基因甲基化、年龄50岁、次全切除术以下的患者的预后因素为13.2个月。结论：我们证实MGMT基因甲基化是GBM患者的一个有效预后因素。我们的研究结果表明，术后早期放疗和高的全切除率或次全切除率可能会进一步改善预后。(C)2012 Elsevier Inc.
Purpose: Recently, cells deficient in O-6-methylguanine-DNA methyltransferase (MGMT) were found to show increased sensitivity to temozolomide (TMZ). We evaluated whether hypermethylation of MGMT was associated with survival in patients with glioblastoma multiforme (GBM).Methods and Materials: We retrospectively analyzed 93 patients with histologically confirmed GBM who received involved-field radiotherapy with TMZ from 2001 to 2008. The median age was 58 years (range, 24-78 years). Surgical resection was total in 39 patients (42%), subtotal in 30 patients (32%), and partial in 17 patients (18%); only a biopsy was performed in 7 patients (8%). Postoperative radiotherapy began within 3 weeks of surgery in 87% of the patients. Radiotherapy doses ranged from 50 to 74 Gy (median, 70 Gy). MGMT gene methylation was determined in 78 patients; MGMT was unmethylated in 43 patients (55%) and methylated in 35 patients (45%). The median follow-up period was 22 months (range, 3-88 months) for all patients.Results: The median overall survival (OS) was 22 months, and progression-free survival (PFS) was 11 months. MGMT gene methylation was an independently significant prognostic factor for both OS (p = 0.002) and PFS (p = 0.008) in multivariate analysis. The median OS was 29 months for the methylated group and 20 months for the unmethylated group. In 35 patients with methylated MGMT genes, the 2-year and 5-year OS rates were 54% and 31%, respectively. Six patients with combined prognostic factors of methylated MGMT genes, age 50 years, and less than subtotal resection was 13.2 months.Conclusion: We confirmed that MGMT gene methylation is a potent prognostic factor in patients with GBM. Our results suggest that early postoperative radiotherapy and a high total/subtotal resection rate might further improve the outcome. (C) 2012 Elsevier Inc.