Department of Radiation Oncology, Yonsei University College of Medicine, Yonsei University Health System, Seoul, Korea.
Int J Radiat Oncol Biol Phys. 2012 Nov 1;84(3):661-7. doi: 10.1016/j.ijrobp.2011.12.086. Epub 2012 Mar 11.
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).
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.
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 total/subtotal resections are all alive 38 to 77 months after operation, whereas the median OS in 8 patients with unmethylated MGMT genes, age >50 years, and less than subtotal resection was 13.2 months.
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.
最近发现 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）表现出更高的敏感性。我们评估了多形性胶质母细胞瘤（GBM）患者中 MGMT 的高甲基化是否与生存相关。
我们回顾性分析了 2001 年至 2008 年间接受含 TMZ 场放疗的 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（42%）行全切除术，30 例（32%）行次全切除术，17 例（18%）行部分切除术；7 例（8%）仅行活检。87%的患者术后放疗在术后 3 周内开始。放疗剂量范围为 50-74Gy（中位数为 70Gy）。对 78 例患者进行了 MGMT 基因甲基化检测；43 例（55%）MGMT 未甲基化，35 例（45%）MGMT 甲基化。所有患者的中位随访时间为 22 个月（范围，3-88 个月）。
中位总生存期（OS）为 22 个月，无进展生存期（PFS）为 11 个月。MGMT 基因甲基化是多因素分析中 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，未甲基化组为 20 个月。在 35 例 MGMT 基因甲基化的患者中，2 年和 5 年 OS 率分别为 54%和 31%。6 例具有 MGMT 基因甲基化、年龄≤50 岁和全/次全切除的联合预后因素的患者，在手术后 38-77 个月均存活，而 8 例 MGMT 基因未甲基化、年龄>50 岁和切除不完全的患者，中位 OS 为 13.2 个月。
我们证实 MGMT 基因甲基化是 GBM 患者的一个有力预后因素。我们的结果表明，术后早期放疗和高全/次全切除率可能进一步改善预后。
