Kickingereder Philipp, Wiestler Benedikt, Graf Markus, Heiland Sabine, Schlemmer Heinz Peter, Wick Wolfgang, Wick Antje, Bendszus Martin, Radbruch Alexander
Department of Neuroradiology, University of Heidelberg Medical Center, Heidelberg, Germany,
J Neurooncol. 2015 Jan;121(2):373-80. doi: 10.1007/s11060-014-1644-6. Epub 2014 Oct 31.
Bevacizumab, an antibody to vascular endothelial growth factor, is commonly used in the setting of recurrent glioblastoma (rGB). The aim of the present study was to evaluate whether dynamic-contrast-enhanced MRI (DCE-MRI) derived microvascular permeability is related to bevacizumab treatment outcome in rGB. Twenty-two patients with rGB underwent DCE-MRI at a median of 2.6 weeks prior initializing bevacizumab therapy. Follow-up MRI-scans (DCE-MRI available for 19/22 patients) were obtained after a median of 9.9 weeks. The volume transfer constant (K(trans))--an estimate related to microvascular permeability--at baseline and voxel-wise-reduction (VWR) in K(trans) at first follow-up were measured from the entire contrast-enhancing tumor (CET) and correlated with progression-free and overall survival (PFS, OS) using uni- and multivariate cox-regression (significance-level p < 0.05). Baseline K(trans) ranged from 0.050 to 0.205 min(-1) (median, 0.109 min(-1)). The VWR in K(trans) ranged from 19.9 to 97.2 % (median, 89.4 %). Patients with lower baseline K(trans) and higher VWR in K(trans) showed significantly longer PFS and OS. Given the strong correlation of VWR in K(trans) and CET-volume changes (Spearman's ρ = -0.73, p < 0.01) both variables were included in a multivariate model. Thereby, neither VWR in K(trans) nor CET-volume changes retained independent significance for PFS or OS. Pre-treatment K(trans) stratifies PFS and OS in patients with bevacizumab-treated rGB. Although early pharmacodynamics changes in K(trans) were not assessed, the VWR in K(trans) at first follow-up had no additional benefit over assessment of CET-volume changes. Further prospective trials are needed to confirm these findings and to elucidate the potential role of pre-treatment K(trans) as a predictive and/or prognostic biomarker.
贝伐单抗是一种针对血管内皮生长因子的抗体，常用于复发性胶质母细胞瘤（rGB）的治疗。本研究的目的是评估动态对比增强磁共振成像（DCE-MRI）得出的微血管通透性是否与rGB患者的贝伐单抗治疗结果相关。22例rGB患者在开始贝伐单抗治疗前的中位时间2.6周时接受了DCE-MRI检查。中位时间9.9周后进行了随访MRI扫描（22例患者中有19例可获得DCE-MRI）。从整个对比增强肿瘤（CET）中测量基线时的容积转运常数（K(trans)）（一种与微血管通透性相关的估计值）以及首次随访时K(trans)的体素级减少量（VWR），并使用单变量和多变量cox回归分析（显著性水平p<0.05）将其与无进展生存期和总生存期（PFS、OS）进行相关性分析。基线K(trans)范围为0.050至0.205 min⁻¹（中位数为0.109 min⁻¹）。K(trans)的VWR范围为19.9%至97.2%（中位数为89.4%）。基线K(trans)较低且K(trans)的VWR较高的患者显示出明显更长的PFS和OS。鉴于K(trans)的VWR与CET体积变化之间存在强相关性（Spearman相关系数ρ=-0.73，p<0.01），这两个变量都被纳入了多变量模型。因此，K(trans)的VWR和CET体积变化对于PFS或OS均未保留独立的显著性。治疗前的K(trans)可对接受贝伐单抗治疗的rGB患者的PFS和OS进行分层。尽管未评估K(trans)的早期药效学变化，但首次随访时K(trans)的VWR相较于CET体积变化评估并无额外益处。需要进一步的前瞻性试验来证实这些发现，并阐明治疗前K(trans)作为预测和/或预后生物标志物的潜在作用。
