Abstract
Background/Objectives: The methylation status of the O6-methylguanine-DNA methyltransferase (MGMT) promoter in gliomas has emerged as a critical biomarker for prognosis and treatment response. Conventional methods for assessing MGMT promoter methylation, such as methylation-specific PCR, are invasive and require tissue sampling. Methods: A comprehensive literature search was performed in compliance with the updated PRISMA 2020 guidelines within electronic databases MEDLINE/PubMed, Scopus, and IEEE Xplore. Search terms, including "MGMT", "methylation", "glioma", "glioblastoma", "machine learning", "deep learning", and "radiomics", were adopted in various MeSH combinations. Original studies in the English, Italian, German, and French languages were considered for inclusion. Results: This review analyzed 34 studies conducted in the last six years, focusing on assessing MGMT methylation status using radiomics (RD), deep learning (DL), or combined approaches. These studies utilized radiological data from the public (e.g., BraTS, TCGA) and private institutional datasets. Sixteen studies focused exclusively on glioblastoma (GBM), while others included low- and high-grade gliomas. Twenty-seven studies reported diagnostic accuracy, with fourteen achieving values above 80%. The combined use of DL and RD generally resulted in higher accuracy, sensitivity, and specificity, although some studies reported lower minimum accuracy compared to studies using a single model. Conclusions: The integration of RD and DL offers a powerful, non-invasive tool for precisely recognizing MGMT promoter methylation status in gliomas, paving the way for enhanced personalized medicine in neuro-oncology. The heterogeneity of study populations, data sources, and methodologies reflected the complexity of the pipeline and machine learning algorithms, which may require general standardization to be implemented in clinical practice.