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MGMT GBM — SCE Medical Oncology MCQ

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ModerateCNS TumoursMGMT GBMSCE Medical Oncology

A 60-year-old man with glioblastoma (IDH-wildtype) has the MGMT promoter methylation status assessed. It is methylated. What is the clinical significance?

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Correct answer: D — MGMT promoter methylation predicts significantly better response to temozolomide and improved survival — methylated GBM patients have median OS ~21 months with standard Stupp protocol vs ~15 months for unmethylated; MGMT status is the strongest molecular predictor of temozolomide benefit

MGMT (O6-methylguanine-DNA methyltransferase) promoter methylation silences the DNA repair gene, making tumour cells more susceptible to temozolomide alkylation damage. Methylated GBM: median OS ~21 months (Stupp protocol). Unmethylated: ~15 months. In elderly patients (>70), MGMT status may guide treatment: methylated → temozolomide; unmethylated → RT alone (NOA-08/Nordic trials).

Reference: NICE NG99; Stupp et al NEJM 2005; Hegi et al NEJM 2005