MGMT methylation may benefit overall survival in patients with moderately vascularized glioblastomas
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ONCOLOGY
MGMT methylation may benefit overall survival in patients with moderately vascularized glioblastomas Elies Fuster-Garcia 1 & David Lorente Estellés 2 & María del Mar Álvarez-Torres 3 & Javier Juan-Albarracín 3 & Eduard Chelebian 3 & Alex Rovira 4 & Cristina Auger Acosta 4 & Jose Pineda 5 & Laura Oleaga 5 & Enrique Mollá-Olmos 6 & Silvano Filice 7 & Paulina Due-Tønnessen 8 & Torstein R. Meling 9,10 & Kyrre E. Emblem 1 & Juan M. García-Gómez 3 Received: 18 June 2020 / Revised: 5 August 2020 / Accepted: 15 September 2020 # The Author(s) 2020
Abstract Objectives To assess the combined role of tumor vascularity, estimated from perfusion MRI, and MGMT methylation status on overall survival (OS) in patients with glioblastoma. Methods A multicentric international dataset including 96 patients from NCT03439332 clinical study were used to study the prognostic relationships between MGMT and perfusion markers. Relative cerebral blood volume (rCBV) in the most vascularized tumor regions was automatically obtained from preoperative MRIs using ONCOhabitats online analysis service. Cox survival regression models and stratification strategies were conducted to define a subpopulation that is particularly favored by MGMT methylation in terms of OS. Results rCBV distributions did not differ significantly (p > 0.05) in the methylated and the non-methylated subpopulations. In patients with moderately vascularized tumors (rCBV < 10.73), MGMT methylation was a positive predictive factor for OS (HR = 2.73, p = 0.003, AUC = 0.70). In patients with highly vascularized tumors (rCBV > 10.73), however, there was no significant effect of MGMT methylation (HR = 1.72, p = 0.10, AUC = 0.56). Conclusions Our results indicate the existence of complementary prognostic information provided by MGMT methylation and rCBV. Perfusion markers could identify a subpopulation of patients who will benefit the most from MGMT methylation. Not considering this information may lead to bias in the interpretation of clinical studies. Key Points • MRI perfusion provides complementary prognostic information to MGMT methylation. • MGMT methylation improves prognosis in glioblastoma patients with moderate vascular profile. • Failure to consider these relations may lead to bias in the interpretation of clinical studies. Keywords Perfusion imaging . Glioblastoma . O(6)-Methylguanine-DNA methyltransferase . Prognostic factors . Temozolomide Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00330-020-07297-4) contains supplementary material, which is available to authorized users. * Elies Fuster-Garcia [email protected]
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Hospital Clínic, Barcelona, Spain
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Hospital Universitario de La Ribera, València, Spain
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Department of Medical Physics, University Hospital of Parma, Parma, Italy
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Department of Radiology, Oslo University Hospital, Oslo, Norway
Instituto Universitario de Tecnologías de la Información y Comunicaciones, Universitat Politècnica de València, València, Spain
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Department of Neurosurgery,
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