MGMT promoter methylation status and prognosis of patients with primary or recurrent glioblastoma treated with carmustine wafers
MGMT promoter methylation status and prognosis of patients with primary or recurrent glioblastoma treated with carmustine wafers
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DOI：
10.3109/02688697.2013.791664
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发表时间：
2013-12-01
影响因子：
1.1
通讯作者：
Giese, A.
中科院分区：
文献类型：
--
作者：
Gutenberg, A.;Bock, H. C.;Giese, A.
O-6-甲基鸟嘌呤-DNA甲基转移酶（MGMT）启动子甲基化在接受卡莫司汀（BCNU）晶片植入治疗的胶质母细胞瘤患者中的预后作用尚不清楚。在这里，我们报告了一项回顾性研究的47例新诊断（30例）或复发（17例）胶质母细胞瘤（WHO IV级）治疗BCNU（双氯乙基亚硝基脲）晶圆。13例新诊断患者仅接受局部BCNU和放疗（一线BCNU），而17例患者额外接受伴随和辅助替莫唑胺（TMZ）放化疗（一线BCNU + TMZ）。在17例接受复发性胶质母细胞瘤（二线BCNU）治疗的患者中，16例接受了放疗，同时接受了TMZ辅助治疗作为初始治疗。与28例非甲基化肿瘤患者相比，19例MGMT启动子甲基化肿瘤患者的中位总生存期（OS）无显著差异（18.9 vs 15.0个月; p = 0.1054）。在一线BCNU + TMZ组中，MGMT启动子甲基化与较长的OS相关（21.0 vs 11.1个月，p = 0.0127），而在其他两个亚组中未检测到显著的生存差异。在整个患者队列或任何三个亚组中，无进展生存期在有和无MGMT启动子甲基化肿瘤患者之间没有显著差异。一线BCNU + TMZ组与一线BCNU组相比，OS无显著差异（18.9 vs 14.7个月），但倾向于出现更多治疗相关不良反应（53% vs 24%，p = 0.105）。总之，在我们的患者队列中，MGMT启动子甲基化显示出延长生存期的非显著趋势。TMZ放化疗联合局部给予BCNU与局部单独给予BCNU相比，没有提供显著的生存获益，但不良反应发生率较高。然而，由于研究的患者数量较少，这些发现需要在更大的患者队列中得到证实。
The prognostic role of O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation in glioblastoma patients treated with carmustine (BCNU) wafer implantation is unclear. Here, we report on a retrospective study of 47 patients with either newly diagnosed (30 patients) or recurrent (17 patients) glioblastoma (WHO grade IV) treated with BCNU (bis-chloroethylnitrosourea) wafers. Thirteen of the newly diagnosed patients received local BCNU and irradiation only (first-line BCNU), while 17 patients additionally received concomitant and adjuvant temozolomide (TMZ) radiochemotherapy (first-line BCNU + TMZ). Of the 17 patients treated for recurrent glioblastoma (second-line BCNU), 16 had received radiotherapy with concomitant and adjuvant TMZ as an initial treatment. Median overall survival (OS) did not significantly differ between 19 patients with MGMT promoter methylated tumors when compared to 28 patients with unmethylated tumors (18.9 vs 15.0 months; p = 0.1054). In the first-line BCNU + TMZ group, MGMT promoter methylation was associated with longer OS (21.0 vs 11.1 months, p = 0.0127), while no significant survival differences were detected in the other two subgroups. Progression-free survival did not significantly differ between patients with and without MGMT promoter methylated tumors in the entire patient cohort or any of the three subgroups. The first-line BCNU + TMZ group showed no significant difference in OS when compared to the first-line BCNU group (18.9 vs 14.7 months), but tended to have more therapy-related adverse effects (53% vs 24%, p = 0.105). In summary, MGMT promoter methylation showed a non-significant trend toward longer survival in our patient cohort. The combination of TMZ radiochemotherapy with local delivery of BCNU did not provide a significant survival benefit compared to local BCNU alone, but was associated with a higher rate of adverse effects. Owing to the small number of patients investigated, however, these findings would need to be corroborated in larger patient cohorts.