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Background  Combined whole-exome sequencing (WES) and somatic copy number alteration (SCNA) information can separate  isocitrate dehydrogenase (IDH)1/2 -wildtype glioblastoma into two prognostic molecular subtypes, which cannot be distinguished by epigenetic or clinical features. The potential for radiographic features to discriminate between these molecular subtypes has yet to be established.    Methods  Radiologic features ( n  = 35 340) were extracted from 46 multisequence, pre-operative magnetic resonance imaging (MRI) scans of  IDH1/2 -wildtype glioblastoma patients from The Cancer Imaging Archive (TCIA), all of whom have corresponding WES/SCNA data. We developed a novel feature selection method that leverages the structure of extracted MRI features to mitigate the dimensionality challenge posed by the disparity between a large number of features and the limited patients in our cohort. Six traditional machine learning classifiers were trained to distinguish molecular subtypes using our feature selection method, which was compared to least absolute shrinkage and selection operator (LASSO) feature selection, recursive feature elimination, and variance thresholding.    Results  We were able to classify glioblastomas into two prognostic subgroups with a cross-validated area under the curve score of 0.80 (±0.03) using ridge logistic regression on the 15-dimensional principle component analysis (PCA) embedding of the features selected by our novel feature selection method. An interrogation of the selected features suggested that features describing contours in the T2 signal abnormality region on the T2-weighted fluid-attenuated inversion recovery (FLAIR) MRI sequence 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.

Radiogenomic modeling predicts survival-associated prognostic groups in glioblastoma