Prognostic and Predictive Value of Integrated Qualitative and Quantitative Magnetic Resonance Imaging Analysis in Glioblastoma

Author:

Verduin MaikelORCID,Primakov Sergey,Compter IngeORCID,Woodruff Henry C.ORCID,van Kuijk Sander M. J.,Ramaekers Bram L. T.ORCID,te Dorsthorst Maarten,Revenich Elles G. M.,ter Laan MarkORCID,Pegge Sjoert A. H.ORCID,Meijer Frederick J. A.ORCID,Beckervordersandforth Jan,Speel Ernst JanORCID,Kusters Benno,de Leng Wendy W. J.,Anten Monique M.,Broen Martijn P. G.,Ackermans Linda,Schijns Olaf E. M. G.,Teernstra Onno,Hovinga Koos,Vooijs Marc A.ORCID,Tjan-Heijnen Vivianne C. G.,Eekers Danielle B. P.,Postma Alida A.,Lambin PhilippeORCID,Hoeben AnnORCID

Abstract

Glioblastoma (GBM) is the most malignant primary brain tumor for which no curative treatment options exist. Non-invasive qualitative (Visually Accessible Rembrandt Images (VASARI)) and quantitative (radiomics) imaging features to predict prognosis and clinically relevant markers for GBM patients are needed to guide clinicians. A retrospective analysis of GBM patients in two neuro-oncology centers was conducted. The multimodal Cox-regression model to predict overall survival (OS) was developed using clinical features with VASARI and radiomics features in isocitrate dehydrogenase (IDH)-wild type GBM. Predictive models for IDH-mutation, 06-methylguanine-DNA-methyltransferase (MGMT)-methylation and epidermal growth factor receptor (EGFR) amplification using imaging features were developed using machine learning. The performance of the prognostic model improved upon addition of clinical, VASARI and radiomics features, for which the combined model performed best. This could be reproduced after external validation (C-index 0.711 95% CI 0.64–0.78) and used to stratify Kaplan–Meijer curves in two survival groups (p-value < 0.001). The predictive models performed significantly in the external validation for EGFR amplification (area-under-the-curve (AUC) 0.707, 95% CI 0.582–8.25) and MGMT-methylation (AUC 0.667, 95% CI 0.522–0.82) but not for IDH-mutation (AUC 0.695, 95% CI 0.436–0.927). The integrated clinical and imaging prognostic model was shown to be robust and of potential clinical relevance. The prediction of molecular markers showed promising results in the training set but could not be validated after external validation in a clinically relevant manner. Overall, these results show the potential of combining clinical features with imaging features for prognostic and predictive models in GBM, but further optimization and larger prospective studies are warranted.

Funder

KWF Kankerbestrijding

Stichting STOPhersentumoren.nl

European Research Council

FP7 Research for the Benefit of SMEs

Eurostars

Horizon 2020

TRANSCAN Joint Transnational Call 2016

Interreg

Publisher

MDPI AG

Subject

Cancer Research,Oncology

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