Clinical analysis shows MGMT promoter methylation has no impact on progression-free survival in IDH-mutant astrocytoma patients.
BACKGROUND: To comprehensively investigate clinical, molecular, radiological, and surgical factors for prediction of progression-free survival (PFS) in patients with isocitrate dehydrogenase (IDH)-mutant astrocytomas. METHODS: A total of 210 patients with newly diagnosed WHO grade 2 to 4 IDH-mutant astrocytomas between 2005 and 2023 were included. Clinical, molecular, radiological, and surgical factors were evaluated. Total, contrast-enhancing, non-enhancing, and necrotic tumor volumes were quantified via automatic volumetric segmentation (cm3). Significant predictors of PFS were identified using univariable and multivariable Cox analyses. RESULTS: The median PFS was 106.8 months, with a 5-year PFS rate of 67.5%. On multivariable analysis, higher initial KPS (hazard ratio [HR] = 0.76, P = .029) remained as a favorable predictor of PFS, while higher WHO grade (grade 3, HR = 1.01, P = .997; grade 4, HR = 2.91, P = .013; reference standard as grade 2, overall P = .032), larger total tumor volume (HR = 1.03, P = .013), and lesser extent of resection (EOR) (subtotal resection, HR = 1.80, P = .043; partial resection, HR = 2.14, P = .014; biopsy, HR = 3.79, P = .008; reference standard as gross total resection, overall P = .015) remained as unfavorable predictors of PFS. Age and MGMT promoter methylation were not significant predictors, while the adverse prognostic impact of WHO grade was primarily driven by WHO grade 4 tumors. CONCLUSIONS: Our work presents a detailed analysis of a large series of IDH-mutant astrocytomas, underscoring the prognostic importance of WHO grade 4, tumor volume, and EOR.
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Cho et al. (2026) studied this question.
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