NIMG-52. RADIOGENOMICS SIGNATURES IN KEY DRIVER GENES IN GLIOBLASTOMA EVALUATED WITH AND WITHOUT THE PRESENCE OF CO-OCCURRING MUTATIONS

PURPOSE Glioblastomas display significant heterogeneity on the molecular level, typically harboring several co-occurring mutations, which likely contributes to failure of molecularly targeted therapeutic approaches. Radiogenomics has emerged as a promising tool for in vivo characterization of this heterogeneity. We derive radiogenomic signatures of four mutations via machine learning (ML) analysis of multiparametric MRI (mpMRI) and evaluate them in the presence and absence of other co-occurring mutations. METHODS We identified a retrospective cohort of 359 IDH-wildtype glioblastoma patients, with available pre-operative mpMRI (T1, T1Gd, T2, T2-FLAIR) scans and targeted next generation sequencing (NGS) data. Radiomic features, including morphologic, histogram, texture, and Gabor wavelet descriptors, were extracted from the mpMRI. Multivariate predictive models were trained using cross-validated SVM with LASSO feature selection to predict mutation status in key driver genes, EGFR, PTEN, TP53, and NF1. ML models and spatial population atlases of genetic mutations were generated for stratification of the tumors (1) with co-occurring mutations versus wildtypes, (2) with exclusive mutations in each driver gene versus the tumors without any mutations in the pathways associated with these genes. RESULTS ML models yielded AUCs of 0.75 (95%CI:0.62-0.88) / 0.87 (95%CI:0.70-1) for co-occurring / exclusive EGFR mutations, 0.69 (95%CI:0.58-0.80) / 0.80 (95%CI:0.61-0.99) for co-occurring / exclusive PTEN mutations, and 0.77 (95%CI:0.65-0.88) / 0.86 (95%CI:0.69-1) for co-occurring / exclusive TP53 cases. Spatial atlases revealed a predisposition of left temporal lobe for NF1 and right frontotemporal region for TP53 in mutually exclusive tumors, which was not observed in the co-occurring mutation atlases. CONCLUSION Our results suggest the presence of distinct radiogenomic signatures of several glioblastoma mutations, which become even more pronounced when respective mutations do not co-occur with other mutations. These in vivo signatures can contribute to pre-operative stratification of patients for molecular targeted therapies, and potentially longitudinal monitoring of mutational changes during treatment.