MGMT promoter methylation status prediction using MRI scans? An extensive experimental evaluation of deep learning models

Med Image Anal. 2023 Dec:90:102989. doi: 10.1016/j.media.2023.102989. Epub 2023 Oct 6.

Abstract

The number of studies on deep learning for medical diagnosis is expanding, and these systems are often claimed to outperform clinicians. However, only a few systems have shown medical efficacy. From this perspective, we examine a wide range of deep learning algorithms for the assessment of glioblastoma - a common brain tumor in older adults that is lethal. Surgery, chemotherapy, and radiation are the standard treatments for glioblastoma patients. The methylation status of the MGMT promoter, a specific genetic sequence found in the tumor, affects chemotherapy's effectiveness. MGMT promoter methylation improves chemotherapy response and survival in several cancers. MGMT promoter methylation is determined by a tumor tissue biopsy, which is then genetically tested. This lengthy and invasive procedure increases the risk of infection and other complications. Thus, researchers have used deep learning models to examine the tumor from brain MRI scans to determine the MGMT promoter's methylation state. We employ deep learning models and one of the largest public MRI datasets of 585 participants to predict the methylation status of the MGMT promoter in glioblastoma tumors using MRI scans. We test these models using Grad-CAM, occlusion sensitivity, feature visualizations, and training loss landscapes. Our results show no correlation between these two, indicating that external cohort data should be used to verify these models' performance to assure the accuracy and reliability of deep learning systems in cancer diagnosis.

Keywords: Deep learning; Glioblastoma; Interpretability; MGMT promoter; Radiogenomics.

MeSH terms

  • Aged
  • Brain Neoplasms* / diagnostic imaging
  • Brain Neoplasms* / genetics
  • DNA Modification Methylases / genetics
  • DNA Modification Methylases / metabolism
  • DNA Modification Methylases / therapeutic use
  • DNA Repair Enzymes / genetics
  • DNA Repair Enzymes / metabolism
  • DNA Repair Enzymes / therapeutic use
  • Deep Learning*
  • Glioblastoma* / diagnostic imaging
  • Glioblastoma* / genetics
  • Humans
  • Magnetic Resonance Imaging / methods
  • Methylation
  • Reproducibility of Results
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism
  • Tumor Suppressor Proteins / therapeutic use

Substances

  • DNA Modification Methylases
  • MGMT protein, human
  • Tumor Suppressor Proteins
  • DNA Repair Enzymes