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. 2026 Jan 27.
doi: 10.1227/neu.0000000000003929. Online ahead of print.

Molecular Features of Glioblastoma Isocitrate Dehydrogenase-Wildtype in Extreme Survival Groups After Supramaximal and Maximal Resection

Angel Bueno  1 , Antonio Dono  1 , Christian Amezquita-Contreras  1 , Kamand Khalaj  2 , Ankush Chandra  1 , Andres Rodriguez  2 , Pavel S Pichardo-Rojas  1 , Sigmund Hsu  1   3 , Mark Amsbaugh  1   3 , Jay-Jiguang Zhu  1   3 , Angel I Blanco  1   3 , Roy F Riascos  2   3 , Leomar Y Ballester  4   5 , Nitin Tandon  1   3 , Yoshua Esquenazi  1   3   6
Affiliations

Molecular Features of Glioblastoma Isocitrate Dehydrogenase-Wildtype in Extreme Survival Groups After Supramaximal and Maximal Resection

Angel Bueno et al. Neurosurgery. .

Abstract

Background and objectives: Glioblastoma (GBM) isocitrate dehydrogenase-wildtype remains a devastating brain tumor with a poor prognosis despite optimal treatment. Even after supramaximal or complete contrast-enhancing (CE) resection, patient outcomes vary significantly, with some experiencing short-term survival (STS) and others long-term survival (LTS). This study aims to identify clinical and molecular markers predicting the survival of patients with GBM in these high-resection categories.

Methods: We retrospectively analyzed patients with newly diagnosed GBM who underwent supramaximal or complete CE resection, followed by next-generation sequencing at our institution (2009-2025). Patients were categorized as STS (survival ≤12 months), non-STS (survival >12 months), or LTS (survival ≥36 months). We compared clinical, radiological, and molecular features between these groups to identify potential prognostic markers.

Results: Among 85 patients who met the inclusion criteria, 24 (28%) were STSs and 61 were non-STS (from which 16 [18.8%] were LTSs), with no significant molecular differences observed between these groups. On comparing STS and LTS patients, CDKN2A/B loss (83.3% vs 43.8%, P = .01) and EGFR amplification (58.3% vs 25%, P = .05) were more frequent in STS patients vs LTS. Tumor location varied, with STS patients having more frontal lobe tumors (45.8%) and LTS patients having more temporal lobe tumors (62.5%). A trend, although not statistically significant, toward increased nonlocal recurrence rates was observed in STS patients (27.2%).

Conclusion: Despite aggressive extent of resection in GBM, the prevalence of STS patients remains notable at ∼28% and survival beyond 3 years remains limited at ∼18.8%. CDKN2A/B loss and EGFR amplification might correlate with shortened survival after supramaximal or complete CE resection. The impact of nonlocal recurrence remains uncertain among STSs. These findings highlight the need for collaborative studies to advance understanding of the biology of GBM as their behavior differs despite aggressive surgical and medical therapies.

Keywords: Glioblastoma IDH-wildtype; Long-term survivors; Molecular features; Next-generation sequencing; Recurrence pattern; Short-term survivors.

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