Robust association between vascular habitats and patient prognosis in glioblastoma: An international multicenter study
Corresponding Author
María del Mar Álvarez-Torres MS
Universitat Politècnica de València, BDSLab, Instituto Universitarios de Tecnologías de la Información y Comunicaciones (ITACA), Valencia, Spain
Address reprint requests to: M.Á.T., Universitat Politècnica de València, ITACA, C/Camino de Vera S/N – Edificio 8G – Acceso B – 1ª Planta, Valencia, Spain 46022. E-mail: [email protected]Search for more papers by this authorJavier Juan-Albarracín MS
Universitat Politècnica de València, BDSLab, Instituto Universitarios de Tecnologías de la Información y Comunicaciones (ITACA), Valencia, Spain
Search for more papers by this authorElies Fuster-Garcia PhD
Oslo University Hospital, Department of Diagnostic Physics, Oslo, Norway
Search for more papers by this authorFuensanta Bellvís-Bataller MS
Universitat Politècnica de València, BDSLab, Instituto Universitarios de Tecnologías de la Información y Comunicaciones (ITACA), Valencia, Spain
Search for more papers by this authorDavid Lorente MD
Hospital Provincial de Castellón, Department of Medical Oncology, Castellón de la Plana, Castellón de la Plana, Spain
Search for more papers by this authorGaspar Reynés MD
Health Research Institute Hospital La Fe, Cancer Research Group, Valencia, Spain
Search for more papers by this authorJaime Font de Mora MD
Instituto de Investigación Sanitaria La Fe, Laboratory of Cellular and Molecular Biology, Valencia, Spain
Search for more papers by this authorFernando Aparici-Robles MD
Hospital Universitari i Politècnic La Fe, Área Clínica de imagen Médica, Valencia, Spain
Search for more papers by this authorCarlos Botella MD
Hospital Universitari i Politècnic La Fe, Área Clínica de Neurociencias, Valencia, Spain
Search for more papers by this authorJose Muñoz-Langa MD
Health Research Institute Hospital La Fe, Cancer Research Group, Valencia, Spain
Search for more papers by this authorRaquel Faubel PhD
Universitat de València, Departament de Fisioteràpia, Valencia, Spain
Search for more papers by this authorSabina Asensio-Cuesta PhD
Universitat Politècnica de València, BDSLab, Instituto Universitarios de Tecnologías de la Información y Comunicaciones (ITACA), Valencia, Spain
Search for more papers by this authorGermán A. García-Ferrando MS
Universitat Politècnica de València, BDSLab, Instituto Universitarios de Tecnologías de la Información y Comunicaciones (ITACA), Valencia, Spain
Search for more papers by this authorEduard Chelebian BS
Universitat Politècnica de València, BDSLab, Instituto Universitarios de Tecnologías de la Información y Comunicaciones (ITACA), Valencia, Spain
Search for more papers by this authorCristina Auger MD
Hospital Vall d'Hebron, Universitat Autònoma de Barcelona, Magnetic Resonance Unit, Department of Radiology, Barcelona, Spain
Search for more papers by this authorAlex Rovira MD
Hospital Vall d'Hebron, Universitat Autònoma de Barcelona, Magnetic Resonance Unit, Department of Radiology, Barcelona, Spain
Search for more papers by this authorEnrique Mollà-Olmos MD
Hospital Universitario de la Ribera, Departamento de Radiodiagnóstico, Alzira, Valencia, Spain
Search for more papers by this authorAntonio J. Revert MD
Hospital de Manises, Manises, Valencia, Spain
Search for more papers by this authorLuaba Tshibanda MD
Centre Hospitalier Universitaire de Liège, Service médical de Radiodiagnostic, Liège, Belgium
Search for more papers by this authorGirolamo Crisi MD
Azienda Ospedaliero-Universitaria di Parma, Neuroradiology, Parma, Italy
Search for more papers by this authorKyrre E. Emblem PhD
Oslo University Hospital, Department of Diagnostic Physics, Oslo, Norway
Search for more papers by this authorDidier Martin PhD
Centre Hospitalier Universitaire de Liege, Service de Neurochirurugie, Liège, Belgium
Search for more papers by this authorPaulina Due-Tønnessen PhD
Oslo University Hospital Rikshospitalet, Department of Radiology, Oslo, Norway
Search for more papers by this authorTorstein R. Meling PhD
Oslo University Hospital, Department of Neurosurgery, Oslo, Norway
Geneva University Hospital, Department of Neurosurgery, Geneva, Switzerland
Search for more papers by this authorSilvano Filice MD
Azienda Ospedaliero-Universitaria di Parma, Medical Physics, Parma, Italy
Search for more papers by this authorCarlos Sáez PhD
Universitat Politècnica de València, BDSLab, Instituto Universitarios de Tecnologías de la Información y Comunicaciones (ITACA), Valencia, Spain
Search for more papers by this authorJuan M. García-Gómez PhD
Universitat Politècnica de València, BDSLab, Instituto Universitarios de Tecnologías de la Información y Comunicaciones (ITACA), Valencia, Spain
Search for more papers by this authorCorresponding Author
María del Mar Álvarez-Torres MS
Universitat Politècnica de València, BDSLab, Instituto Universitarios de Tecnologías de la Información y Comunicaciones (ITACA), Valencia, Spain
Address reprint requests to: M.Á.T., Universitat Politècnica de València, ITACA, C/Camino de Vera S/N – Edificio 8G – Acceso B – 1ª Planta, Valencia, Spain 46022. E-mail: [email protected]Search for more papers by this authorJavier Juan-Albarracín MS
Universitat Politècnica de València, BDSLab, Instituto Universitarios de Tecnologías de la Información y Comunicaciones (ITACA), Valencia, Spain
Search for more papers by this authorElies Fuster-Garcia PhD
Oslo University Hospital, Department of Diagnostic Physics, Oslo, Norway
Search for more papers by this authorFuensanta Bellvís-Bataller MS
Universitat Politècnica de València, BDSLab, Instituto Universitarios de Tecnologías de la Información y Comunicaciones (ITACA), Valencia, Spain
Search for more papers by this authorDavid Lorente MD
Hospital Provincial de Castellón, Department of Medical Oncology, Castellón de la Plana, Castellón de la Plana, Spain
Search for more papers by this authorGaspar Reynés MD
Health Research Institute Hospital La Fe, Cancer Research Group, Valencia, Spain
Search for more papers by this authorJaime Font de Mora MD
Instituto de Investigación Sanitaria La Fe, Laboratory of Cellular and Molecular Biology, Valencia, Spain
Search for more papers by this authorFernando Aparici-Robles MD
Hospital Universitari i Politècnic La Fe, Área Clínica de imagen Médica, Valencia, Spain
Search for more papers by this authorCarlos Botella MD
Hospital Universitari i Politècnic La Fe, Área Clínica de Neurociencias, Valencia, Spain
Search for more papers by this authorJose Muñoz-Langa MD
Health Research Institute Hospital La Fe, Cancer Research Group, Valencia, Spain
Search for more papers by this authorRaquel Faubel PhD
Universitat de València, Departament de Fisioteràpia, Valencia, Spain
Search for more papers by this authorSabina Asensio-Cuesta PhD
Universitat Politècnica de València, BDSLab, Instituto Universitarios de Tecnologías de la Información y Comunicaciones (ITACA), Valencia, Spain
Search for more papers by this authorGermán A. García-Ferrando MS
Universitat Politècnica de València, BDSLab, Instituto Universitarios de Tecnologías de la Información y Comunicaciones (ITACA), Valencia, Spain
Search for more papers by this authorEduard Chelebian BS
Universitat Politècnica de València, BDSLab, Instituto Universitarios de Tecnologías de la Información y Comunicaciones (ITACA), Valencia, Spain
Search for more papers by this authorCristina Auger MD
Hospital Vall d'Hebron, Universitat Autònoma de Barcelona, Magnetic Resonance Unit, Department of Radiology, Barcelona, Spain
Search for more papers by this authorAlex Rovira MD
Hospital Vall d'Hebron, Universitat Autònoma de Barcelona, Magnetic Resonance Unit, Department of Radiology, Barcelona, Spain
Search for more papers by this authorEnrique Mollà-Olmos MD
Hospital Universitario de la Ribera, Departamento de Radiodiagnóstico, Alzira, Valencia, Spain
Search for more papers by this authorAntonio J. Revert MD
Hospital de Manises, Manises, Valencia, Spain
Search for more papers by this authorLuaba Tshibanda MD
Centre Hospitalier Universitaire de Liège, Service médical de Radiodiagnostic, Liège, Belgium
Search for more papers by this authorGirolamo Crisi MD
Azienda Ospedaliero-Universitaria di Parma, Neuroradiology, Parma, Italy
Search for more papers by this authorKyrre E. Emblem PhD
Oslo University Hospital, Department of Diagnostic Physics, Oslo, Norway
Search for more papers by this authorDidier Martin PhD
Centre Hospitalier Universitaire de Liege, Service de Neurochirurugie, Liège, Belgium
Search for more papers by this authorPaulina Due-Tønnessen PhD
Oslo University Hospital Rikshospitalet, Department of Radiology, Oslo, Norway
Search for more papers by this authorTorstein R. Meling PhD
Oslo University Hospital, Department of Neurosurgery, Oslo, Norway
Geneva University Hospital, Department of Neurosurgery, Geneva, Switzerland
Search for more papers by this authorSilvano Filice MD
Azienda Ospedaliero-Universitaria di Parma, Medical Physics, Parma, Italy
Search for more papers by this authorCarlos Sáez PhD
Universitat Politècnica de València, BDSLab, Instituto Universitarios de Tecnologías de la Información y Comunicaciones (ITACA), Valencia, Spain
Search for more papers by this authorJuan M. García-Gómez PhD
Universitat Politècnica de València, BDSLab, Instituto Universitarios de Tecnologías de la Información y Comunicaciones (ITACA), Valencia, Spain
Search for more papers by this authorAbstract
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.
Supporting Information
| Filename | Description |
|---|---|
| jmri26958-sup-0001-supinfo.docxWord 2007 document , 831.9 KB | Table S1 Summary of the magnetic resonance imaging (MRI) acquisition parameters per center. Table S2.1: Summary of patients excluded and included per hospital. Table S2.2: Analyses of the differences among centers in terms of age and gender. ANOVA test and post-hoc comparison Table S3.1: Results of the pair-wise Mann Whitney analyses for HAT markers Table S3.2: Results of the pair-wise Mann Whitney analyses for LAT markers Table S3.3: Results of the pair-wise Mann Whitney analyses for IPE markers Table S3.4: Results of the pair-wise Mann Whitney analyses for VPE markers Table S4: Cox regression results obtained by performing the analysis with the OS and rCBVmax data from each center. Figure S1: Kaplan-Meier estimated survival functions for the populations of each center stratified into groups according to high or low rCBVmax in LAT, divided by the threshold calculated with the data of all the center (cut off threshold of 5.31). Figure S2: Kaplan-Meier estimated survival functions for the populations of each center stratified into groups according to high or low rCBVmax in IPE, divided by the threshold calculated with the data of all the center (cut off threshold of 1.92). |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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