Abstract

Abstract BACKGROUND Previously, we have shown that combined whole-exome sequencing (WES) and genome-wide somatic copy number alteration (SCNA) information can separate IDH1/2-wildtype glioblastoma into two prognostic molecular subtypes (Group 1 and Group 2) and that these subtypes cannot be distinguished by epigenetic or clinical features. However, the potential for radiographic features to discriminate between these molecular subtypes has not been established. METHODS Radiogenomic features (n=35,400) were extracted from 46 multiparametric, pre-operative magnetic resonance imaging (MRI) of IDH1/2-wildtype glioblastoma patients from The Cancer Imaging Archive, all of whom have corresponding WES and SCNA data in The Cancer Genome Atlas. We developed a novel feature selection method that leverages the structure of extracted radiogenomic MRI features to mitigate the dimensionality challenge posed by the disparity between the number of features and patients in our cohort. Seven traditional machine learning classifiers were trained to distinguish Group 1 versus Group 2 using our feature selection method. Our feature selection was compared to lasso feature selection, recursive feature elimination, and variance thresholding. RESULTS We are able to classify Group 1 versus Group 2 glioblastomas with a cross-validated area under the curve (AUC) score of 0.82 using ridge logistic regression and our proposed feature selection method, which reduces the size of our feature set from 35,400 to 288. An interrogation of the selected features suggests that features describing contours in the T2 abnormality region on the FLAIR MRI modality may best distinguish these two groups from one another. CONCLUSIONS We successfully trained a machine learning model that allows for relevant targeted feature extraction from standard MRI to accurately predict molecularly-defined risk-stratifying IDH1/2-wildtype glioblastoma patient groups. This algorithm may be applied to future prospective studies to assess the utility of MRI as a surrogate for costly prognostic genomic studies.

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