Abstract

PurposeIn glioma, molecular alterations are closely associated with disease prognosis. This study aimed to develop a radiomics-based multiple gene prediction model incorporating mutual information of each genetic alteration in glioblastoma and grade 4 astrocytoma, IDH-mutant.MethodsFrom December 2014 through January 2020, we enrolled 418 patients with pathologically confirmed glioblastoma (based on the 2016 WHO classification). All selected patients had preoperative MRI and isocitrate dehydrogenase (IDH) mutation, O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation, epidermal growth factor receptor amplification, and alpha-thalassemia/mental retardation syndrome X-linked (ATRX) loss status. Patients were randomly split into training and test sets (7:3 ratio). Enhancing tumor and peritumoral T2-hyperintensity were auto-segmented, and 660 radiomics features were extracted. We built binary relevance (BR) and ensemble classifier chain (ECC) models for multi-label classification and compared their performance. In the classifier chain, we calculated the mean absolute Shapley value of input features.ResultsThe micro-averaged area under the curves (AUCs) for the test set were 0.804 and 0.842 in BR and ECC models, respectively. IDH mutation status was predicted with the highest AUCs of 0.964 (BR) and 0.967 (ECC). The ECC model showed higher AUCs than the BR model for ATRX (0.822 vs. 0.775) and MGMT promoter methylation (0.761 vs. 0.653) predictions. The mean absolute Shapley values suggested that predicted outcomes from the prior classifiers were important for better subsequent predictions along the classifier chains.ConclusionWe built a radiomics-based multiple gene prediction chained model that incorporates mutual information of each genetic alteration in glioblastoma and grade 4 astrocytoma, IDH-mutant and performs better than a simple bundle of binary classifiers using prior classifiers’ prediction probability.

Highlights

  • Glioblastoma, the most common primary malignant brain parenchymal tumor, is challenging to treat [1]

  • According to the upcoming 2021 WHO Classification of Tumors of the Central Nervous System (CNS) [9], previously called glioblastoma, isocitrate dehydrogenase (IDH)-mutant is designated as astrocytoma, IDH-mutant, WHO grade 4 and glioblastoma should be diagnosed in the setting of IDH wildtype

  • O-6-methylguanineDNA methyltransferase (MGMT) promoter methylation and epidermal growth factor receptor (EGFR) alteration are related to prognosis

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Summary

Introduction

Glioblastoma, the most common primary malignant brain parenchymal tumor, is challenging to treat [1]. A comprehensive molecular characterization of glioblastoma showed that most tumors harbor recurrent molecular alterations disrupting core pathways involved in the regulation of growth, cell cycle, DNA repair, apoptosis, and control of chromatin state [2]. These recurrent and relevant genomic variants continue to be targets for drug development [3,4,5]. Several studies have investigated that quantitative image features from preoperative imaging of gliomas can be used to predict IDH and alpha-thalassemia/mental retardation syndrome X-linked (ATRX) mutations, EGFR amplification, and MGMT promoter methylation [10,11,12,13,14]

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