Vivian L. Smith Department of Neurosurgery, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA.
Department of Pathology and Laboratory Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA.
J Neurooncol. 2021 Mar;152(1):153-162. doi: 10.1007/s11060-020-03689-0. Epub 2021 Jan 25.
Despite aggressive treatment, glioblastoma invariably recurs. The optimal treatment for recurrent glioblastoma (rGBM) is not well defined. Stereotactic radiosurgery (SRS) for rGBM has demonstrated favorable outcomes for selected patients; however, its efficacy in molecular GBM subtypes is unknown. We sought to identify genetic alterations that predict response/outcomes from SRS in rGBM-IDH-wild-type (IDH-WT).
rGBM-IDH-WT patients undergoing SRS at first recurrence and tested by next-generation sequencing (NGS) were reviewed (2009-2018). Demographic, clinical, and molecular characteristics were evaluated. NGS interrogating 205-genes was performed. Primary outcome was survival from GK-SRS assessed by Kaplan-Meier method and multivariable Cox proportional-hazards.
Sixty-three lesions (43-patients) were treated at 1st recurrence. Median age was 61-years. All patients were treated with resection and chemoradiotherapy. Median time from diagnosis to 1st recurrence was 8.7-months. Median cumulative volume was 2.895 cm and SRS median marginal dose was 18 Gy (median isodose-54%). Bevacizumab was administered in 81.4% patients. PFS from SRS was 12.9-months. Survival from SRS was 18.2-months. PTEN-mutant patients had a longer PFS (p = 0.049) and survival from SRS (p = 0.013) in multivariable analysis. Although no statistically significant PTEN-mutants patients had higher frequency of radiation necrosis (21.4% vs. 3.4%) and lower in-field recurrence (28.6% vs. 37.9%) compared to PTEN-WT patients.
SRS is a safe and effective treatment option for selected rGBM-IDH-WT patients following first recurrence. rGBM-IDH-WT harboring PTEN-mutation have improved survival with salvage SRS compared to PTEN-WT patients. PTEN may be used as a molecular biomarker to identify a subset of rGBM patients who may benefit the most from SRS.
尽管进行了积极的治疗，胶质母细胞瘤仍不可避免地会复发。复发性胶质母细胞瘤（rGBM）的最佳治疗方法尚未明确。对于特定患者，立体定向放射外科（SRS）治疗 rGBM 已显示出良好的结果；然而，其在分子 GBM 亚型中的疗效尚不清楚。我们试图确定预测 IDH-WT 型复发性胶质母细胞瘤 SRS 反应/结果的遗传改变。
回顾性分析 2009 年至 2018 年间在首次复发时接受 SRS 治疗并经下一代测序（NGS）检测的 rGBM-IDH-WT 患者。评估了患者的人口统计学、临床和分子特征。进行了 205 个基因的 NGS 检测。主要结局是通过 Kaplan-Meier 方法和多变量 Cox 比例风险评估从 GK-SRS 中获得的生存。
63 个病灶（43 例患者）在首次复发时接受了治疗。中位年龄为 61 岁。所有患者均接受了手术切除和放化疗。从诊断到首次复发的中位时间为 8.7 个月。中位累积体积为 2.895cm，SRS 中位边缘剂量为 18Gy（中位等剂量 54%）。81.4%的患者使用了贝伐单抗。SRS 的无进展生存期为 12.9 个月。SRS 的总生存期为 18.2 个月。多变量分析显示，PTEN 突变患者的 PFS（p=0.049）和 SRS 生存（p=0.013）更长。尽管在统计学上，PTEN 突变患者的放射性坏死发生率（21.4%比 3.4%）更高，而在野复发率（28.6%比 37.9%）更低，但与 PTEN-WT 患者相比，PTEN 突变患者没有更高的频率。
SRS 是复发性 IDH-WT 型胶质母细胞瘤患者在首次复发后的一种安全有效的治疗选择。与 PTEN-WT 患者相比，携带 PTEN 突变的 rGBM-IDH-WT 患者接受挽救性 SRS 治疗后，生存时间得到改善。PTEN 可能作为一种分子生物标志物，用于识别最有可能从 SRS 中获益的胶质母细胞瘤患者亚组。
