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

María Del Mar Álvarez-Torres, Javier Juan-Albarracín, Elies Fuster-Garcia, Fuensanta Bellvís-Bataller, David Lorente, Gaspar Reynés, Jaime Font de Mora, Fernando Aparici-Robles, Carlos Botella, Jose Muñoz-Langa, Raquel Faubel, Sabina Asensio-Cuesta, Germán A García-Ferrando, Eduard Chelebian, Cristina Auger, Jose Pineda, Alex Rovira, Laura Oleaga, Enrique Mollà-Olmos, Antonio J Revert, Luaba Tshibanda, Girolamo Crisi, Kyrre E Emblem, Didier Martin, Paulina Due-Tønnessen, Torstein R Meling, Silvano Filice, Carlos Sáez, Juan M García-Gómez, María Del Mar Álvarez-Torres, Javier Juan-Albarracín, Elies Fuster-Garcia, Fuensanta Bellvís-Bataller, David Lorente, Gaspar Reynés, Jaime Font de Mora, Fernando Aparici-Robles, Carlos Botella, Jose Muñoz-Langa, Raquel Faubel, Sabina Asensio-Cuesta, Germán A García-Ferrando, Eduard Chelebian, Cristina Auger, Jose Pineda, Alex Rovira, Laura Oleaga, Enrique Mollà-Olmos, Antonio J Revert, Luaba Tshibanda, Girolamo Crisi, Kyrre E Emblem, Didier Martin, Paulina Due-Tønnessen, Torstein R Meling, Silvano Filice, Carlos Sáez, Juan M García-Gómez

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.

Keywords: glioblastoma; multicenter study; overall survival; perfusion DSC; vascularity.

© 2019 International Society for Magnetic Resonance in Medicine.

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