Robust association between vascular habitats and patient prognosis in glioblastoma: An international multicenter study

Abstract

Background Glioblastoma (GBM) is the most aggressive primary brain tumor, characterized by a heterogeneous and abnormal vascularity. Subtypes of vascular habitats within the tumor and edema can be distinguished: high angiogenic tumor (HAT), low angiogenic tumor (LAT), infiltrated peripheral edema (IPE), and vasogenic peripheral edema (VPE). Purpose To validate the association between hemodynamic markers from vascular habitats and overall survival (OS) in glioblastoma patients, considering the intercenter variability of acquisition protocols. Study Type Multicenter retrospective study. Population In all, 184 glioblastoma patients from seven European centers participating in the NCT03439332 clinical study. Field Strength/Sequence 1.5T (for 54 patients) or 3.0T (for 130 patients). Pregadolinium and postgadolinium‐based contrast agent‐enhanced T1‐weighted MRI, T2‐ and FLAIR T2‐weighted, and dynamic susceptibility contrast (DSC) T2* perfusion. Assessment We analyzed preoperative MRIs to establish the association between the maximum relative cerebral blood volume (rCBVmax) at each habitat with OS. Moreover, the stratification capabilities of the markers to divide patients into "vascular" groups were tested. The variability in the markers between individual centers was also assessed. Statistical Tests Uniparametric Cox regression; Kaplan–Meier test; Mann–Whitney test. Results The rCBVmax derived from the HAT, LAT, and IPE habitats were significantly associated with patient OS (P < 0.05; hazard ratio [HR]: 1.05, 1.11, 1.28, respectively). Moreover, these markers can stratify patients into "moderate‐" and "high‐vascular" groups (P < 0.05). The Mann–Whitney test did not find significant differences among most of the centers in markers (HAT: P = 0.02–0.685; LAT: P = 0.010–0.769; IPE: P = 0.093–0.939; VPE: P = 0.016–1.000). Data Conclusion The rCBVmax calculated in HAT, LAT, and IPE habitats have been validated as clinically relevant prognostic biomarkers for glioblastoma patients in the pretreatment stage. This study demonstrates the robustness of the hemodynamic tissue signature (HTS) habitats to assess the GBM vascular heterogeneity and their association with patient prognosis independently of intercenter variability. Level of Evidence: 3 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2020;51:1478–1486.

Higher vascularity at infiltrated peripheral edema differentiates proneural glioblastoma subtype

“…These could affect the potential relationships with molecular markers. Nonetheless determining the IPE habitat by an automated method for calculating the maximum of the cerebral blood volume to perform seems robust enough for our purpose, as shown by Álvarez-Torres et al 23 . Finally, despite having significant results, the sample size available in the dataset may be a statistical limitation.…”

“…The prognosis potential of the rCBV in glioblastoma at the ET ROI has been extensively studied 14,34,35 . The prognosis potential of the rCBV in glioblastoma in the non-enhancing region was also suggested in some studies 15,23,36 . Jain et al performed a survival analysis estimating HR for rCBV in both the enhancing and non-enhancing areas adjusting them for the Verhaak molecular subtypes and using the same database as this study 19 .…”

“…All the cases were processed using the Hemodynamic Tissue Signature service found in the ONCOhabitats platform 24 . It provides a reproducible 23 and automated methodology to define ROI, based on the vascular properties of the lesion, which enables for a more accurate study of peripheral regions. After preprocessing, the ONCOhabitats service delineates for habitats within the lesion based on unsupervised analysis.…”

Higher vascularity at infiltrated peripheral edema differentiates proneural glioblastoma subtype

“…All the cases were processed using the Hemodynamic Tissue Signature service found in the ONCOhabitats platform [24]. It provides a reproducible [23] and automated methodology to define habitats withing the glioblastoma, based on the vascular properties of the lesion, as shown in Fig 1. Morphological sequences are used for segmentation of enhancing tumor and edema. The resulting segmentation together with DSC perfusion maps are used to obtain the vascular habitats.…”

“…The purpose of this article is to assess the correlation between the vascularity present at the infiltrated peripheral edema habitat at preoperative stage and Verhaak molecular classification. To do so, we propose the use of a multicentrically validated [23] automatic open service named ONCOhabitats (https://www.oncohabitats.upv.es) proposed by Juan-Albarracín et al [15,24,25]. To ensure the comparability of our study, the analysis was performed on the TCGA-GBM open database [26], which contains MR images and molecular information.…”