Chiranth Shivani, Fougner Vincent, Christensen Ib Jarle, Trip Anouk Kirsten, Christiansen Terkel, Nørøxe Dorte Schou, Yde Christina Westmose, Berthelsen Anne Kiil, Hasselbalch Benedikte, Lassen Ulrik, Poulsen Hans Skovgaard, Urup Thomas
The DCCC Brain Tumor Center, Rigshospitalet, Copenhagen, Denmark.
Department of Oncology, Rigshospitalet, Copenhagen, Denmark.
Neurooncol Adv. 2025 May 7;7(1):vdaf092. doi: 10.1093/noajnl/vdaf092. eCollection 2025 Jan-Dec.
Infiltrative growth is a hallmark of glioblastoma (GBM) and is a major factor in therapeutic failure. Distant progression is a surrogate marker for infiltrative growth and genetic variants predictive of distant progression may serve as novel treatment targets. The aim was to identify clinical, molecular, radiographic, and genetic factors associated with distant progression in GBM patients.
From our prospective database, all consecutive GBM wild type patients receiving standard therapy (Stupp regimen) from 2016 to 2021 at Rigshospitalet (Denmark) were included. Distant progression was defined as a new contrast-enhancing lesion > 2 cm from the initial lesion. Clinical, molecular, radiographic, and genomic covariates were assessed for association with time to distant progression using Cox analysis.
This single-center study included 353 patients, of whom 303 patients had radiographic progression. Distant progression was found in 66 patients (22%) and was associated with poor post-progression survival ( < .001). Unmethylated (hazard ratio [HR]: 2.54, 95% confidence interval [CI]: 1.62-3.97, < .001), and multicentric disease at diagnosis (HR: 2.32, 95% CI: 1.28-4.20, = .005) were associated with a shorter time to distant progression. In patients with a genomic tumor profile ( = 204), the gene alteration was identified as an independent predictor of distant progression (HR: 3.48, 95% CI: 1.48-8.21, = .004) and poor survival.
Distant progression is an aggressive progression pattern associated with a poor prognosis. Unmethylated multicentric disease, and alteration independently predict distant progression. alteration may serve as a predictive biomarker for targeted treatment.
浸润性生长是胶质母细胞瘤（GBM）的一个标志，也是治疗失败的主要因素。远处进展是浸润性生长的替代标志物，预测远处进展的基因变异可能成为新的治疗靶点。目的是确定与GBM患者远处进展相关的临床、分子、影像学和遗传因素。
从我们的前瞻性数据库中，纳入了2016年至2021年在丹麦里格霍斯医院接受标准治疗（Stupp方案）的所有连续GBM野生型患者。远处进展定义为距初始病变>2 cm的新的强化病变。使用Cox分析评估临床、分子、影像学和基因组协变量与远处进展时间的相关性。
这项单中心研究纳入了353例患者，其中303例患者有影像学进展。66例患者（22%）出现远处进展，且与进展后生存期较差相关（P<0.001）。未甲基化的MGMT（风险比[HR]：2.54，95%置信区间[CI]：1.62-3.97，P<0.001）以及诊断时的多中心疾病（HR：2.32，95%CI：1.28-4.20，P=0.005）与较短的远处进展时间相关。在有基因组肿瘤图谱的患者（n=204）中，TERT基因改变被确定为远处进展（HR：3.48，95%CI：1.48-8.21，P=0.004）和生存期较差的独立预测因素。
远处进展是一种与预后不良相关的侵袭性进展模式。未甲基化的MGMT、多中心疾病和TERT改变独立预测远处进展。TERT改变可能作为靶向治疗的预测生物标志物。
