ArticleJournal of neuro-oncology2025
A multi-center, clinical analysis of IDH-mutant gliomas, WHO Grade 4: implications for prognosis and clinical trial design.
Article in Journal of neuro-oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Review
- Contemporary practice patterns in IDH-mutant glioma management: a multidisciplinary multi-institutional survey.Journal of neuro-oncology · 2026Article
- MGMT promoter methylation status for glioblastoma: defining the clinically relevant cut-off value for pyrosequencing.Journal of neuro-oncology · 2026Article
- Accessibility to molecular studies in gliomas: a challenge for precision medicine in low-resource countries.Frontiers in oncology · 2026Article
- Loss ofJournal of Cancer · 2026Article
- The impacts of the COVID-19 pandemic on IDH-wildtype glioblastoma survival: A Surveillance, Epidemiology, and End Results Analysis.Neuro-oncology practice · 2025Article
- Severe Chemoradiotherapy Toxicity in a Pediatric Patient with Leigh Syndrome and Grade IV Isocitrate Dehydrogenase-Mutant Astrocytoma: A Case Report.The American journal of case reports · 2025Article
- CDKN2A/B status versus morphology in diagnosing WHO grade 4 IDH-mutated astrocytomas: what is the clinical relevance?Journal of neuro-oncology · 2025Article
- Prognostic and predictive determinants in high-grade gliomas: integrating tumor-intrinsic biology with patient and system-level factors.Frontiers in neurology · 2025Review
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Authors and funding
13 authors.
Funding
Abstract
purposeMutations in the Isocitrate Dehydrogenase (IDH) genes, IDH1 or IDH2, define a group of adult diffuse gliomas associated with a younger age at diagnosis and better prognosis than IDH wild-type glioblastoma. Within IDH mutant gliomas, a small fraction of astrocytic tumors present with grade 4 histologic features and poor prognosis. In molecular studies, homozygous deletion of CDKN2A/B is independently predictive of poor prognosis and short survival. As a consequence, 2021 WHO classification now also recognizes this molecular feature, CDKN2A/B deletion, as sufficient for classifying an astrocytoma as IDH-mutant, WHO Grade 4, regardless of histological grading. Here, we investigate outcomes of patients with WHO Grade 4 IDH-mutant astrocytoma both with and without CDKN2A/B deletion, to compare these groups and evaluate clinical and radiographic factors that contribute to survival.
methodsWe retrospectively identified 79 patients with IDH-mutant astrocytoma with CDKN2A/B deletion detected at initial diagnosis across five international institutions as well as a comparison group of 51 patients with IDH-mutant, astrocytoma, histologically Grade 4 without detectable CDKN2A/B deletion. We assembled clinical and radiographic features for all patients.
resultsWe find that CDKN2A/B deletion was associated with significantly worse overall survival (OS; p = 0.0004) and progression-free survival (PFS; p = 0.0026), with median OS of 5.0 years and PFS of 3.0 years, compared to 10.1 and 5.0 years for tumors with a grade 4 designation based only on histologic criteria. Multivariate analysis confirmed CDKN2A/B deletion as a strong negative prognosticator for both OS (HR = 3.51, p < 0.0001) and PFS (HR = 2.35, p = 0.00095). In addition, in tumors with CDKN2A/B deletion, preoperative contrast enhancement is a significant predictor of worse OS (HR 2.19, 95% CI 1.22-3.93, p = 0.0090) and PFS (HR = 1.74, 95% CI = 1.02-2.97, p = 0.0420).
conclusionsThese findings underscore the severe prognostic impact of CDKN2A/B deletion in IDH-mutant astrocytomas and highlight the need for further refinement of tumor prognostic categorization. Our results provide a key benchmark of baseline patient outcomes for therapeutic trials, underscoring the importance of CDKN2A/B status assessment, in addition to histologic grading, in clinical trial design and therapeutic decision-making for IDH-mutant astrocytoma patients.
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