Abstract

ObjectivesOxygen 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.MethodsWe 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.ResultsThe 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).ConclusionsThe 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.

Highlights

  • Astrocytoma is the most common type of glioma, and carries a poor prognosis [1, 2]

  • We investigated the utility of a multi-sequence and multi-habitat MR radiomics signature as a preoperative and non-invasive biomarker of methylguanine-DNA methyltransferase (MGMT) methylation prediction in patients with grade II–IV astrocytomas, and discuss the prognostic implications for survival stratification on TMZ chemotherapy response

  • No significant difference was shown for the MGMT methylation status distribution in the training and validation cohorts (p = 0.156)

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Summary

Introduction

The average survival time ranges from 17 weeks to 3 years [2, 3]. A subgroup of grade II-IV astrocytoma patients with oxygen 6-methylguanine-DNA methyltransferase (MGMT) promoter methylation show good responses to temozolomide (TMZ) chemotherapy and improved survival after treatment, which underscored the role of MGMT as a judicious molecular biomarker with a prognostic implication [4,5,6,7]. Preoperative identification of MGMT promoter methylation would be of great clinical significance in selecting potential patients benefiting from TMZ chemotherapy, assisting with planning the therapy regime. There is an urgent need in clinical practice for preoperative and non-invasive prediction of MGMT promoter methylation in grade II-IV astrocytomas

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