Department of Neurosurgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Department of Neurosurgery, Graduate School of Medicine, Osaka University, Suita, Japan.
Cancer Med. 2021 May;10(10):3177-3187. doi: 10.1002/cam4.3860. Epub 2021 Apr 10.
Accumulating evidence from recent molecular diagnostic studies has indicated the prognostic significance of various genetic markers for patients with glioblastoma (GBM). To evaluate the impact of such genetic markers on prognosis, we retrospectively analyzed the outcomes of patients with IDH-wildtype GBM in our institution. In addition, to assess the impact of bevacizumab (BEV) treatment, we compared overall survival (OS) between the pre- and post-BEV eras.
We analyzed the data of 100 adult patients (over 18 years old) with IDH-wildtype GBM from our database between February 2006 and October 2018. Genetic markers, such as MGMT methylation status, EGFR amplification, CDKN2A homozygous deletion, and clinical factors were analyzed by evaluating the patients' OS.
CDKN2A homozygous deletion showed no significant impact on OS in patients with methylated MGMT status (p = 0.5268), whereas among patients with unmethylated MGMT status, there was a significant difference in OS between patients with and without CDKN2A homozygous deletion (median OS: 14.7 and 16.9 months, respectively, p = 0.0129). This difference was more evident in the pre-BEV era (median OS: 10.1 and 15.6 months, respectively, p = 0.0351) but has become nonsignificant in the post-BEV era (median OS: 16.0 and 16.9 months, respectively, p = 0.1010) due to OS improvement in patients with CDKN2A homozygous deletion. However, these findings could not be validated in The Cancer Genome Atlas cohort.
MGMT and CDKN2A status subdivided our cohort into three race-specific groups with different prognoses. Our findings indicate that BEV approval in Japan led to OS improvement exclusively for patients with concurrent unmethylated MGMT status and CDKN2A homozygous deletion.
最近的分子诊断研究积累的证据表明，各种遗传标志物对胶质母细胞瘤（GBM）患者具有预后意义。为了评估这些遗传标志物对预后的影响，我们回顾性分析了本机构 IDH 野生型 GBM 患者的结局。此外，为了评估贝伐单抗（BEV）治疗的影响，我们比较了 BEV 治疗前后的总生存期（OS）。
我们分析了 2006 年 2 月至 2018 年 10 月期间我们数据库中 100 例 IDH 野生型 GBM 成年患者（年龄大于 18 岁）的数据。通过评估患者的 OS，分析了 MGMT 甲基化状态、EGFR 扩增、CDKN2A 纯合缺失等遗传标志物和临床因素对患者 OS 的影响。
CDKN2A 纯合缺失在甲基化 MGMT 状态的患者中对 OS 没有显著影响（p=0.5268），而在未甲基化 MGMT 状态的患者中，CDKN2A 纯合缺失的患者与无 CDKN2A 纯合缺失的患者之间的 OS 存在显著差异（中位 OS：分别为 14.7 和 16.9 个月，p=0.0129）。这种差异在 BEV 治疗前更为明显（中位 OS：分别为 10.1 和 15.6 个月，p=0.0351），但在 BEV 治疗后变得不显著（中位 OS：分别为 16.0 和 16.9 个月，p=0.1010），因为 CDKN2A 纯合缺失的患者 OS 得到改善。然而，这些发现无法在癌症基因组图谱队列中得到验证。
MGMT 和 CDKN2A 状态将我们的队列分为三个具有不同预后的种族特异性亚组。我们的研究结果表明，BEV 在日本的批准仅使同时具有未甲基化 MGMT 状态和 CDKN2A 纯合缺失的患者的 OS 得到改善。
