Abstract

Simple SummaryGlioblastoma (GBM) is the most malignant primary brain tumor, for which improving patient outcome is limited by a substantial amount of tumor heterogeneity. Magnetic resonance imaging (MRI) in combination with machine learning offers the possibility to collect qualitative and quantitative imaging features which can be used to predict patient prognosis and relevant tumor markers which can aid in selecting the right treatment. This study showed that combining these MRI features with clinical features has the highest prognostic value for GBM patients; this model performed similarly in an independent GBM cohort, showing its reproducibility. The prediction of tumor markers showed promising results in the training set but not could be validated in the independent dataset. This study shows the potential of using MRI to predict prognosis and tumor markers, but further optimization and prospective studies are warranted.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.

Highlights

  • Glioblastoma (GBM) is the most malignant type of primary brain cancer with an incidence of 2–3 cases per 100,000 [1]

  • As a proof-of-concept study, this study investigated the capability of VASARI and radiomics features to link phenotype to genotype and predict clinically relevant molecular markers, IDH1-mutation, Methylguanine methyltransferase (MGMT)-methylation and Epidermal growth factor receptor (EGFR) amplification, by machine learning approaches

  • By extracting radiomics features from the whole tumor and the surrounding area of edema we identified several features that are associated with intratumor heterogeneity

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Summary

Introduction

Glioblastoma (GBM) is the most malignant type of primary brain cancer with an incidence of 2–3 cases per 100,000 [1]. A median survival of fifteen months is achieved with multimodal treatment [2] with a five-year overall relative survival of only 6.8% [3] Despite this intensive treatment by neurosurgical intervention, concurrent chemoradiation and adjuvant temozolomide (TMZ) [2], GBM is still considered incurable and recurrence is inevitable. Further characterization of GBM has led to the introduction of the 2016 updated world health organization (WHO) classification of central nervous system tumors [4]. This classification integrates histopathological and morphological examination of the tumor with molecular markers [5].

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