ArticleNeuro-oncology2024
No benefit from TMZ treatment in glioblastoma with truly unmethylated MGMT promoter: Reanalysis of the CE.6 and the pooled Nordic/NOA-08 trials in elderly glioblastoma patients.
Article in Neuro-oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed.
- Molecularly matched targeted therapies plus radiotherapy in glioblastoma: the phase 1/2a NNature medicine · 2025Trial
- The Role of Noncoding RNA in MGMT-Positive Glioblastoma: A Narrative Review.Cancer medicine · 2026Review
- MGMT promoter methylation across glioma subtypes: biological relevance, treatment response, and survival outcomes.Molecular biology reports · 2026Review
- Label-Free Raman Spectroscopy Reveals Metabolic Signatures Associated with MGMT Promoter Methylation Status in Glioblastoma.Analytical chemistry · 2026Article
- Spatial-temporal recurrence patterns of grade 4 glioma using deep learning integrated multiparametric MRI and molecular pathology.NPJ precision oncology · 2026Article
- MGMT promoter methylation status for glioblastoma: defining the clinically relevant cut-off value for pyrosequencing.Journal of neuro-oncology · 2026Article
- Role of non-coding RNAs in OOncology letters · 2026Review
- Outcomes of inpatient chemoradiotherapy for patients with newly diagnosed glioblastoma and significant functional impairment.Neuro-oncology practice · 2026Article
- Bevacizumab-Functionalized Exosome-Associated Chitosan Nanocomposite for Temozolomide Delivery and Apoptosis-Related Transcriptional Modulation in Experimental Glioma.International journal of nanomedicine · 2026Article
- 20(S)-protopanaxadiol enhances temozolomide responsiveness in MGMT-expressing glioblastoma: Wnt/β-catenin attenuation and MGMT downregulation.Frontiers in medicine · 2026Article
- Mapping the global research landscape and innovations on elderly glioma: a bibliometric analysis.Frontiers in oncology · 2026Article
- Progress in the study of molecular markers in the prognosis assessment and recurrence patterns of glioblastoma.Cancer biology & therapy · 2025Review
- Glioblastoma in adults: A Society for Neuro-Oncology (SNO) and European Society of Neuro-Oncology (EANO) consensus review on current management and future directions.Neuro-oncology · 2025Review
- Point/counterpoint: Upfront BRAF inhibition for adult BRAF-mutant high-grade gliomas.Neuro-oncology · 2025Article
- Real-world survival and prognostic factors in WHO 2021 classified gliomas treated with chemo-radiotherapy.Scientific reports · 2025Article
- Circadian variation in MGMT promoter methylation and expression predicts sensitivity to temozolomide in glioblastoma.Journal of neuro-oncology · 2025Article
- Targeting molecular vulnerabilities in glioblastoma.Nature medicine · 2025Article
- Sonodynamic Therapy With Orally Absorbable Nanomedicine for Brain Tumor.Brain tumor research and treatment · 2025Review
- Article
- Glioblastoma: From Pathophysiology to Novel Therapeutic Approaches.Biomedicines · 2025Review
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Abstract
backgroundThe treatment of elderly/ frail patients with glioblastoma is a balance between avoiding undue toxicity, while not withholding effective treatment. It remains debated, whether these patients should receive combined chemo-radiotherapy with temozolomide (RT/TMZ→TMZ) regardless of the O6-methylguanine DNA methyltransferase gene promoter (MGMTp) methylation status. MGMT is a well-known resistance factor blunting the treatment effect of TMZ, by repairing the most genotoxic lesion. Epigenetic silencing of the MGMTp sensitizes glioblastoma to TMZ. For risk-adapted treatment, it is of utmost importance to accurately identify patients, who will not benefit from TMZ treatment.
methodsHere, we present a reanalysis of the clinical trials CE.6 and the pooled NOA-08 and Nordic trials in elderly glioblastoma patients that compared RT to RT/TMZ→TMZ, or RT to TMZ, respectively. For 687 patients with available MGMTp methylation data, we applied a cutoff discerning truly unmethylated glioblastoma, established in a pooled analysis of 4 clinical trials for glioblastoma, with RT/TMZ→TMZ treatment, using the same quantitative methylation-specific MGMTp PCR assay.
resultsWhen applying this restricted cutoff to the elderly patient population, we confirmed that glioblastoma with truly unmethylated MGMTp derived no benefit from TMZ treatment. In the Nordic/NOA-08 trials, RT was better than TMZ, suggesting little or no benefit from TMZ.
conclusionsFor evidence-based treatment of glioblastoma patients validated MGMTp methylation assays should be used that accurately identify truly unmethylated patients. Respective stratified management of patients will reduce toxicity without compromising outcomes and allow testing of more promising treatment options.
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