Radiation Oncology, University of Maryland Medical Center, Baltimore, MD, USA.
Radiation Oncology, Washington University, St. Louis, MO, USA.
J Neurooncol. 2017 Sep;134(2):331-338. doi: 10.1007/s11060-017-2529-2. Epub 2017 Jun 22.
A recent nomogram for glioblastoma (GBM) was designed to incorporate methylguanine-DNA methyltransferase (MGMT) methylation status in trial patients receiving temozolomide. Since clinical trial patients are strictly selected, compared to the general population, we performed a multi-institutional, external, independent assessment of the nomogram. Consecutive adult patients with supratentorial GBM diagnosed between June 2007 and December 2014 who initiated TMZ-based concurrent chemoradiotherapy (CRT) and were not enrolled on RTOG 0525 or 0825 were eligible. We collected age, gender, MGMT status, performance status, resection extent, race, and tumor site and Cox regression analysis of overall survival (OS) was conducted with the 1-year nomogram-predicted survival (NPS). The predictive accuracy was quantified by the concordance index (c-index) as well as by separating patients into quintile-groups of the population distribution of NPS and comparing mean NPS and observed OS. Of 514 patients with GBM, 309 had all nomogram factors. Median OS was 18.7 months. NPS and observed OS demonstrated a c-index of 0.695. On univariate analysis, the NPS and all included factors except gender were significant. On multivariable analysis (MVA) the only significant factor for worse survival was lower NPS. When separated into quintile-groups of NPS, the observed survival was slightly better than the predicted survival for all but the worst prognostic group. Our multi-institutional cohort provides independent external validation of a novel GBM nomogram incorporating MGMT methylation status. No individual factor included in the nomogram retained significance on MVA after adjusting for NPS.
最近设计了一种胶质母细胞瘤(GBM)的列线图,用于纳入替莫唑胺治疗的临床试验患者中甲基鸟嘌呤-DNA 甲基转移酶(MGMT)甲基化状态。由于临床试验患者是严格选择的,与一般人群相比,我们对该列线图进行了多机构、外部、独立评估。连续的成年患者,诊断为幕上 GBM,诊断时间为 2007 年 6 月至 2014 年 12 月,接受 TMZ 为基础的同期放化疗(CRT),未参加 RTOG 0525 或 0825。我们收集了年龄、性别、MGMT 状态、表现状态、切除程度、种族和肿瘤部位,并对总体生存(OS)进行了 Cox 回归分析,使用 1 年列线图预测的生存(NPS)。预测准确性通过一致性指数(c-index)以及将患者分为 NPS 人群分布的五分位数组,并比较平均 NPS 和观察到的 OS 来量化。在 514 名 GBM 患者中,有 309 名患者具有所有列线图因素。中位 OS 为 18.7 个月。NPS 和观察到的 OS 显示 c-index 为 0.695。单因素分析中,NPS 和除性别以外的所有纳入因素均有意义。多变量分析(MVA)中,唯一与生存较差相关的因素是较低的 NPS。当按 NPS 的五分位数分组时,除最差预后组外,观察到的生存略好于预测生存。我们的多机构队列提供了一种新型 GBM 列线图的独立外部验证,该列线图纳入了 MGMT 甲基化状态。在调整 NPS 后,列线图中没有任何单独的因素在 MVA 中保留意义。