基于分子标志物的胶质母细胞瘤手术：新诊断的 IDH-1 野生型胶质母细胞瘤中切除和 MGMT 启动子甲基化的影响。
Surgery for Glioblastoma in Light of Molecular Markers: Impact of Resection and MGMT Promoter Methylation in Newly Diagnosed IDH-1 Wild-Type Glioblastomas.
机构信息
Department of Neurosurgery, University Hospital Frankfurt, Goethe-University, Frankfurt, Germany.
Stroke Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health (NINDS/NIH), Bethesda, Maryland.
出版信息
Neurosurgery. 2019 Jan 1;84(1):190-197. doi: 10.1093/neuros/nyy049.
BACKGROUND
Previous studies addressing the influence of surgery on the outcome of patients with glioblastomas (GBM) have not addressed molecular markers. The value of surgery versus the tumor's major biological markers remains unclear.
OBJECTIVE
We investigate the extent of resection as a prognosticator for patients with newly diagnosed primary GBM with the incorporation of molecular diagnostics as per the updated WHO 2016 diagnostic criteria for GBM.
METHODS
Patients with newly diagnosed GBM who underwent resection were prospectively included within a database. We analyzed patients with newly diagnosed GBM and excluded patients who presented with IDH1 R132H mutations. Gross total resection (GTR) was defined as complete removal of enhancing disease.
RESULTS
One hundred seventy-five patients were included within the analysis. One hundred four patients (59.4%) had GTR, 71 patients (40.6%) had subtotal or partial resection. Eighty patients (45.7%) displayed O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation, 95 patients (54.3%) showed no MGMT promoter methylation. In Cox regression analysis, MGMT promoter methylation (hazard ratio [HR] 1.55; 95% confidence interval [CI], 1.01-2.19; P = .0133) and GTR (HR 1.48; 95% CI, 1.06-2.07; P = .0206) were significantly associated with favorable progression-free survival. MGMT promoter methylation (HR 2.13; 95% CI, 1.45-3.12; P = .0001) and GTR (HR 1.81; 95% CI, 1.24-2.63; P = .002) were associated with favorable overall survival (OS). Of other risk factors analyzed, age (>60 vs ≤ 60 yr) was significantly associated with progression-free survival (HR 1.60; 95% CI, 1.14-2.24; P = .006) and OS (HR 2.19; 95% CI, 1.51-3.19; P < .0001).
CONCLUSION
GTR and MGMT promoter methylation are independent prognosticators for improved overall and progression-free survival in a homogeneous cohort of newly diagnosed patients with IDH wild-type glioblastoma.
背景
之前研究手术对胶质母细胞瘤（GBM）患者结局的影响时并未涉及分子标志物。手术的价值与肿瘤的主要生物学标志物之间的关系仍不明确。
目的
我们根据世界卫生组织（WHO）2016 年 GBM 诊断标准纳入分子诊断，调查新诊断原发性 GBM 患者的切除范围作为预后指标。
方法
前瞻性纳入数据库中接受手术的新诊断 GBM 患者。我们分析了新诊断为 GBM 的患者，并排除了 IDH1 R132H 突变的患者。大体全切除（GTR）定义为完全切除增强病变。
结果
175 例患者纳入分析。104 例（59.4%）患者行 GTR，71 例（40.6%）患者行次全或部分切除。80 例（45.7%）患者显示 O6-甲基鸟嘌呤-DNA 甲基转移酶（MGMT）启动子甲基化，95 例（54.3%）患者未显示 MGMT 启动子甲基化。在 Cox 回归分析中，MGMT 启动子甲基化（风险比 [HR] 1.55；95%置信区间 [CI] 1.01-2.19；P =.0133）和 GTR（HR 1.48；95% CI，1.06-2.07；P =.0206）与无进展生存期（PFS）改善显著相关。MGMT 启动子甲基化（HR 2.13；95% CI，1.45-3.12；P =.0001）和 GTR（HR 1.81；95% CI，1.24-2.63；P =.002）与总生存期（OS）改善相关。在分析的其他风险因素中，年龄（＞60 岁与≤60 岁）与 PFS（HR 1.60；95% CI，1.14-2.24；P =.006）和 OS（HR 2.19；95% CI，1.51-3.19；P <.0001）显著相关。
结论
在 IDH 野生型胶质母细胞瘤新诊断患者同质队列中，GTR 和 MGMT 启动子甲基化是改善总生存期和无进展生存期的独立预后指标。
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