Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Department of Neurosurgery, University of Pennsylvania, Philadelphia, PA, USA.
J Neurooncol. 2019 Nov;145(2):321-328. doi: 10.1007/s11060-019-03298-6. Epub 2019 Sep 21.
Young adults with isocitrate-dehydrogenase wild-type (IDH-WT) glioblastoma (GBM) represent a rare, understudied population compared to pediatric high-grade glioma, IDH-mutant GBM, or IDH-WT GBM in older patients. We aimed to explore the prognostic impact of epidermal growth factor receptor copy number gain (EGFR CN gain), one of the most common genetic alterations in IDH-WT glioma, in young adults with IDH-WT GBM.
We performed a retrospective cohort study of patients 18-45 years old with newly diagnosed, IDH-WT GBM whose tumors underwent next-generation sequencing at our institution between 2014 and 2018. The impact of EGFR CN gain on time to tumor progression (TTP) and overall survival (OS) was assessed. A validation cohort of patients 18-45 years old with IDH-WT GBM was analyzed from The Cancer Genome Atlas (TCGA).
Ten of 28 patients (36%) from our institution had EGFR CN gain, which was associated with shorter TTP (median 6.5 vs. 11.9 months; p = 0.06) and OS (median 16.3 vs. 23.5 months; p = 0.047). The negative prognostic impact of EGFR CN gain on OS persisted in a multivariate model (HR 6.40, 95% CI 1.3-31.0, p = 0.02). In the TCGA cohort (N = 43), EGFR CN gain was associated with shorter TTP and worse OS, although these did not reach statistical significance (TTP, median 11.5 vs. 14.4 months, p = 0.18; OS, median 23.6 vs. 27.8 months; p = 0.18).
EGFR CN gain may be associated with inferior outcomes in young adults with newly diagnosed, IDH-WT GBM, suggesting a potential role for targeting EGFR in this population.
与小儿高级别胶质瘤、IDH 突变型 GBM 或老年 IDH-WT GBM 相比，IDH-WT 胶质母细胞瘤（GBM）的年轻患者是一个罕见且研究较少的人群。本研究旨在探讨表皮生长因子受体拷贝数增加（EGFR CN 增加）对 IDH-WT 年轻成人 GBM 患者的预后影响，EGFR CN 增加是 IDH-WT 胶质瘤中最常见的遗传改变之一。
我们对在我院接受下一代测序的年龄在 18-45 岁之间的新诊断 IDH-WT GBM 患者进行了回顾性队列研究，这些患者的肿瘤在 2014 年至 2018 年之间进行了研究。评估 EGFR CN 增加对肿瘤进展时间（TTP）和总生存期（OS）的影响。对来自癌症基因组图谱（TCGA）的 18-45 岁 IDH-WT GBM 患者的验证队列进行了分析。
本研究中我院的 28 名患者中有 10 名（36%）存在 EGFR CN 增加，这与较短的 TTP（中位 6.5 与 11.9 个月；p=0.06）和 OS（中位 16.3 与 23.5 个月；p=0.047）相关。在多变量模型中，EGFR CN 增加对 OS 的负预后影响仍然存在（HR 6.40，95%CI 1.3-31.0，p=0.02）。在 TCGA 队列（N=43）中，EGFR CN 增加与较短的 TTP 和较差的 OS 相关，尽管未达到统计学意义（TTP，中位 11.5 与 14.4 个月，p=0.18；OS，中位 23.6 与 27.8 个月，p=0.18）。
EGFR CN 增加可能与新诊断的 IDH-WT GBM 的年轻成人患者的不良预后相关，这表明在该人群中靶向 EGFR 可能具有潜在作用。
