Impact of IDH mutation and MGMT methylation as Independent prognostic markers in uniformly treated high grade glioma Patients: A Real-World evidence in the Indian Population.
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IDH-mutant (IDHmt) high-grade gliomas (HGG) differ significantly from IDH-wildtype (IDHwt) HGG, or glioblastoma (GBM). MGMT promoter methylation (MGMTp) is an established prognostic marker in GBM, but its role in IDHmt HGG remains unclear. We evaluated the prognostic impact of IDH mutation and MGMTp in 395 uniformly treated HGG patients in India. All patients underwent maximal safe resection followed by adjuvant radiotherapy and concurrent plus maintenance temozolomide (TMZ). MGMTp was assessed by methylation-specific PCR, and IDH1/2 mutations by immunohistochemistry and targeted sequencing. Median age was 50 years; median follow-up was 63 months. IDH mutations were present in 15.4 % of patients, and MGMTp in 36.7 %. Median overall survival (OS) was 19 months; 2-year OS was 41.5 %. Age > 50 years (HR 1.77, p < 0.001), <6 cycles of TMZ (HR 2.3, p < 0.001), and IDHwt status (HR 3.02, p < 0.001) predicted poorer outcomes. MGMTp status did not impact OS in IDHmt patients (p = 0.97). However, in IDHwt patients, unmethylated status was associated with worse OS (HR 3.66, p < 0.001) compared to methylated (HR 2.16, p = 0.009). These findings reaffirm the prognostic significance of IDH mutations and MGMTp methylation in GBM, underscoring their relevance in clinical stratification and treatment planning.