A multi-sequence and habitat-based MRI radiomics signature for preoperative prediction of MGMT promoter methylation in astrocytomas with prognostic implication

Eur Radiol. 2019 Feb;29(2):877-888. doi: 10.1007/s00330-018-5575-z. Epub 2018 Jul 23.

Abstract

Objectives: Oxygen 6-methylguanine-DNA methyltransferase (MGMT) promoter methylation is a significant prognostic biomarker in astrocytomas, especially for temozolomide (TMZ) chemotherapy. This study aimed to preoperatively predict MGMT methylation status based on magnetic resonance imaging (MRI) radiomics and validate its value for evaluation of TMZ chemotherapy effect.

Methods: We retrospectively reviewed a cohort of 105 patients with grade II-IV astrocytomas. Radiomic features were extracted from the tumour and peritumoral oedema habitats on contrast-enhanced T1-weighted images, T2-weighted fluid-attenuated inversion recovery images and apparent diffusion coefficient (ADC) maps. The following radiomics analysis was structured in three phases: feature reduction, signature construction and discrimination statistics. A fusion radiomics signature was finally developed using logistic regression modelling. Predictive performance was compared between the radiomics signature, previously reported clinical factors and ADC parameters. Validation was additionally performed on a time-independent cohort (n = 31). The prognostic value of the signature on overall survival for TMZ chemotherapy was explored using Kaplan Meier estimation.

Results: The fusion radiomics signature exhibited supreme power for predicting MGMT promoter methylation, with area under the curve values of 0.925 in the training cohort and 0.902 in the validation cohort. Performance of the radiomics signature surpassed that of clinical factors and ADC parameters. Moreover, the radiomics approach successfully divided patients into high-risk and low-risk groups for overall survival after TMZ chemotherapy (p = 0.03).

Conclusions: The proposed radiomics signature accurately predicted MGMT promoter methylation in patients with astrocytomas, and achieved survival stratification for TMZ chemotherapy, thus providing a preoperative basis for individualised treatment planning.

Key points: • Radiomics using magnetic resonance imaging can preoperatively perform satisfactory prediction of MGMT methylation in grade II-IV astrocytomas. • Habitat-based radiomics can improve efficacy in predicting MGMT methylation status. • Multi-sequence radiomics signature has the power to evaluate TMZ chemotherapy effect.

Keywords: Astrocytoma; Diagnostic imaging; Methylation; Prognosis; ROC curve.

MeSH terms

  • Antineoplastic Agents, Alkylating / therapeutic use
  • Astrocytoma / diagnostic imaging*
  • Astrocytoma / drug therapy
  • Astrocytoma / genetics
  • Astrocytoma / pathology
  • Biomarkers, Tumor*
  • Brain Neoplasms / diagnostic imaging*
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / genetics
  • Brain Neoplasms / pathology
  • DNA Methylation*
  • DNA Modification Methylases / genetics*
  • DNA Repair Enzymes / genetics*
  • Female
  • Humans
  • Image Enhancement / methods
  • Image Interpretation, Computer-Assisted
  • Kaplan-Meier Estimate
  • Logistic Models
  • Magnetic Resonance Imaging / methods*
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Preoperative Care / methods*
  • Prognosis
  • Promoter Regions, Genetic*
  • Retrospective Studies
  • Temozolomide / therapeutic use
  • Tumor Suppressor Proteins / genetics*

Substances

  • Antineoplastic Agents, Alkylating
  • Biomarkers, Tumor
  • Tumor Suppressor Proteins
  • DNA Modification Methylases
  • MGMT protein, human
  • DNA Repair Enzymes
  • Temozolomide