A Multimodal Knowledge-Based Deep Learning Approach for MGMT Promoter Methylation Identification

Abstract

Glioblastoma Multiforme (GBM) is considered one of the most aggressive malignant tumors, characterized by a tremendously low survival rate. Despite alkylating chemotherapy being typically adopted to fight this tumor, it is known that O(6)-methylguanine-DNA methyltransferase (MGMT) enzyme repair abilities can antagonize the cytotoxic effects of alkylating agents, strongly limiting tumor cell destruction. However, it has been observed that MGMT promoter regions may be subject to methylation, a biological process preventing MGMT enzymes from removing the alkyl agents. As a consequence, the presence of the methylation process in GBM patients can be considered a predictive biomarker of response to therapy and a prognosis factor. Unfortunately, identifying signs of methylation is a non-trivial matter, often requiring expensive, time-consuming, and invasive procedures. In this work, we propose to face MGMT promoter methylation identification analyzing Magnetic Resonance Imaging (MRI) data using a Deep Learning (DL) based approach. In particular, we propose a Convolutional Neural Network (CNN) operating on suspicious regions on the FLAIR series, pre-selected through an unsupervised Knowledge-Based filter leveraging both FLAIR and T1-weighted series. The experiments, run on two different publicly available datasets, show that the proposed approach can obtain results comparable to (and in some cases better than) the considered competitor approach while consisting of less than 0.29% of its parameters. Finally, we perform an eXplainable AI (XAI) analysis to take a little step further toward the clinical usability of a DL-based approach for MGMT promoter detection in brain MRI.