Abstract
Background/Objectives: Glioblastoma (GBM) is a highly aggressive primary central nervous system tumor with a median survival of 14 months. MGMT (O6-methylguanine-DNA methyltransferase) promoter methylation status is a key biomarker as a prognostic indicator and a predictor of chemotherapy response in GBM. Patients with MGMT methylated disease progress later and survive longer (median survival rate 22 vs. 15 months, respectively) as compared to patients with MGMT unmethylated disease. Patients with GBM undergo an MRI of the brain prior to diagnosis and following surgical resection for radiation therapy planning and ongoing follow-up. There is currently no imaging biomarker for GBM. Studies have attempted to connect MGMT methylation status to MRI imaging appearance to determine if brain MRI can be leveraged to provide MGMT status information non-invasively and more expeditiously. Methods: Artificial intelligence (AI) can identify MRI features that are not distinguishable to the human eye and can be linked to MGMT status. We employed the UPenn-GBM dataset patients for whom methylation status was available (n = 146), employing a novel radiomic method grounded in hybrid feature selection and weighting to predict MGMT methylation status. Results: The best MGMT classification and feature selection result obtained resulted in a mean accuracy rate value of 81.6% utilizing 101 selected features and five-fold cross-validation. Conclusions: This compared favorably with similar studies in the literature. Validation with external datasets remains critical to enhance generalizability and propagate robust results while reducing bias. Future directions include multi-channel data integration with radiomic features and deep and ensemble learning methods to improve predictive performance.