ArticleActa neuropathologica2024
Improved prognostic stratification of patients with isocitrate dehydrogenase-mutant astrocytoma.
Article in Acta neuropathologica, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 2 of them syntheses that pooled it.
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Who cites it
37 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Homozygous CDKN2A/B deletions in low- and high-grade glioma: a meta-analysis of individual patient data and predictive values of p16 immunohistochemistry testing.Acta neuropathologica communications · 2024Pooled it
- The IDH paradox: Meta-analysis of alkylating chemotherapy in IDH-wild type and -mutant lower grade gliomas.Neuro-oncology · 2024Pooled it
- A Phase 1/2 Study of Disulfiram and Copper With Concurrent Radiation Therapy and Temozolomide for Patients With Newly Diagnosed Glioblastoma.International journal of radiation oncology, biology, physics · 2024Trial
- MGMT promoter methylation as a molecular biomarker in neuro-oncology: current practices, challenges, and future directions.Journal of neuro-oncology · 2026Review
- IDH1-mutant vaccine in newly diagnosed astrocytoma: final analysis of the multicenter, single-arm, open-label, first-in-human phase 1 NOA16 trial.Nature cancer · 2026Article
- Isocitrate Dehydrogenase-Mutant Astrocytomas: Risk Stratification and Therapeutic Advance.MedComm · 2026Review
- Prognostic relevance of resection at first recurrence in isocitrate dehydrogenase mutant lower-grade glioma: results from a retrospective, single-center, volumetric analysis.Journal of neuro-oncology · 2026Observational
- SERPINA3 facilitates malignant progression and remodels tumor immune microenvironment in glioma.Biochemistry and biophysics reports · 2026Article
- Clinicopathologic and FISH-Based Evaluation of CDKN2A/B and EGFR in IDH Mutant Astrocytomas.Noro psikiyatri arsivi · 2026Article
- Translational role of molecular biomarkers in developing targeted therapies for central nervous system tumors.IBRO neuroscience reports · 2025Review
- Loss of global DNA hypermethylation is prognostic in IDH-mutant and 1p/19q-codeleted oligodendrogliomas.Acta neuropathologica · 2025Article
- Clinical, molecular, and radiological predictors of prognosis in newly diagnosed astrocytoma, IDH-mutant, WHO grade 4.Neuro-oncology · 2025Article
- LINE-1 hypomethylation in cell-free DNA of high-grade glioma patients correlates with tissue levels and is associated with reduced DNMT1 and H4K20me3 expression.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- CDKN2A/B status versus morphology in diagnosing WHO grade 4 IDH-mutated astrocytomas: what is the clinical relevance?Journal of neuro-oncology · 2025Article
- Advances in IDH-mutant glioma management: IDH inhibitors, clinical implications of INDIGO trial, and future perspectives.Future oncology (London, England) · 2025Review
- An Analysis for IDH-Mutant Grade 4 Astrocytoma Based on WHO CNS 5: Implication of Clinical Practice.Annals of clinical and translational neurology · 2025Article
- Canonical amplifications and CDKN2A/B loss refine IDH1/2-mutant astrocytoma prognosis.Neuro-oncology · 2025Article
- The prognostic impact of CDKN2A/B hemizygous deletions in IDH-mutant glioma.Neuro-oncology · 2025Article
- The molecular history of IDH-mutant astrocytomas without adjuvant treatment.Brain pathology (Zurich, Switzerland) · 2025Article
- IDH-mutant astrocytomas with primitive neuronal component have a distinct methylation profile and a higher risk of leptomeningeal spread.Acta neuropathologica · 2025Article
Corrections and comments
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Authors and funding
18 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Prognostic factors and standards of care for astrocytoma, isocitrate dehydrogenase (IDH)-mutant, CNS WHO grade 4, remain poorly defined. Here we sought to explore disease characteristics, prognostic markers, and outcome in patients with this newly defined tumor type. We determined molecular biomarkers and assembled clinical and outcome data in patients with IDH-mutant astrocytomas confirmed by central pathology review. Patients were identified in the German Glioma Network cohort study; additional cohorts of patients with CNS WHO grade 4 tumors were identified retrospectively at two sites. In total, 258 patients with IDH-mutant astrocytomas (114 CNS WHO grade 2, 73 CNS WHO grade 3, 71 CNS WHO grade 4) were studied. The median age at diagnosis was similar for all grades. Karnofsky performance status at diagnosis inversely correlated with CNS WHO grade (p < 0.001). Despite more intensive treatment upfront with higher grade, CNS WHO grade was strongly prognostic: median overall survival was not reached for grade 2 (median follow-up 10.4 years), 8.1 years (95% CI 5.4-10.8) for grade 3, and 4.7 years (95% CI 3.4-6.0) for grade 4. Among patients with CNS WHO grade 4 astrocytoma, median overall survival was 5.5 years (95% CI 4.3-6.7) without (n = 58) versus 1.8 years (95% CI 0-4.1) with (n = 12) homozygous CDKN2A deletion. Lower levels of global DNA methylation as detected by LINE-1 methylation analysis were strongly associated with CNS WHO grade 4 (p < 0.001) and poor outcome. MGMT promoter methylation status was not prognostic for overall survival. Histomolecular stratification based on CNS WHO grade, LINE-1 methylation level, and CDKN2A status revealed four subgroups of patients with significantly different outcomes. In conclusion, CNS WHO grade, global DNA methylation status, and CDKN2A homozygous deletion are prognostic in patients with IDH-mutant astrocytoma. Combination of these parameters allows for improved prediction of outcome. These data aid in designing upcoming trials using IDH inhibitors.
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