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Accepted Articles of Congress

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  • MGMT Promoter Methylation as a Predictor of Temozolomide Response and Survival in Glioblastoma: A Systematic Review

  • Kimia Heydariyar,1,* Hori Ghaneialvar,2 Omid Raiesi,3 Alireza Vasiee,4
    1. Student Research Committee, Faculty of Medicine, Ilam University of Medical Sciences, Ilam, Iran
    2. Biotechnology and Medicinal Plants Research Center, Ilam University of Medical Sciences, Ilam, Iran
    3. Omid Raiesi
    4. Department of Nursing, Faculty of Nursing and Midwifery, Ilam University of Medical Sciences, Ilam, Iran


  • Introduction: O6-Methylguanine-DNA methyltransferase (MGMT) promoter methylation silences a key DNA repair enzyme and sensitizes glioblastoma to alkylating agents. Temozolomide (TMZ) is standard adjuvant therapy, yet only a subset of patients derives prolonged benefit. We systematically evaluated the association between MGMT promoter methylation and TMZ response, progression-free survival (PFS), and overall survival (OS) in adult glioblastoma.
  • Methods: PubMed, EMBASE, Web of Science, and Scopus databases were searched from inception through June 2025 for clinical studies reporting MGMT methylation status and TMZ outcomes in newly diagnosed glioblastoma. Search terms included (“MGMT” OR “O6-methylguanine-DNA methyltransferase”) AND (“temozolomide”) AND (“glioblastoma”) and their related MeSH terms. Two reviewers independently screened 1,324 titles/abstracts, extracted data on objective response rate (ORR), median PFS, median OS, and hazard ratios (HR), and assessed study quality using the Newcastle–Ottawa Scale for cohorts and the Cochrane Risk of Bias tool for randomized trials.
  • Results: Twelve studies comprising 1,842 patients (methylated n=828, unmethylated n=1,014; median follow-up 20.4 months) met inclusion criteria. MGMT promoter methylation prevalence was 45.0% (95% CI 42.5–47.5). Methylated tumors exhibited a pooled ORR to TMZ of 48.3% versus 21.7% in unmethylated tumors (OR 3.21; 95% CI 2.45–4.21; p<0.01). Median PFS was 7.8 months (95% CI 7.1–8.5) in the methylated cohort versus 4.6 months (95% CI 4.0–5.2) in unmethylated (HR 0.49; 95% CI 0.42–0.57; p<0.001), and median OS was 18.5 months (95% CI 17.2–19.8) versus 12.3 months (95% CI 11.1–13.5) (HR 0.56; 95% CI 0.49–0.64; p<0.01).
  • Conclusion: MGMT promoter methylation confers a threefold higher response rate and approximately 50% reduction in progression and death risk with temozolomide in glioblastoma, validating its role as a predictive biomarker to guide adjuvant therapy.
  • Keywords: glioblastoma; MGMT promoter methylation; temozolomide

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