Prognostic impact of PTEN status in recurrent IDH-wildtype glioblastoma receiving second-line therapy

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ID: 322649
2026
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Abstract
Abstract Background Recurrent IDH-wildtype glioblastoma has a poor prognosis, and no validated molecular biomarker guides second-line treatment choices. Because PTEN alterations are frequent in glioblastoma and may influence therapy resistance, we assessed their association with outcomes in patients with recurrence of IDH-wildtype glioblastoma. Methods This is a retrospective study including consecutive adults with first recurrence of IDH-wildtype glioblastoma treated between 2019 and 2022 with regorafenib, nitrosoureas, or bevacizumab. PTEN alterations were assessed by NGS. Overall survival was analyzed using Kaplan-Meier estimates and multivariable Cox models adjusted for clinically relevant covariates. An exploratory weighted analysis compared regorafenib and nitrosoureas in PTEN wild-type tumors. Results Among 226 patients, 128 (57%) had PTEN alterations. The prevalence was higher in patients who received regorafenib (66%) than in those treated with nitrosourea (48%) or bevacizumab (55%). In univariate analyses, PTEN alteration was associated with shorter survival with regorafenib (median OS, 9.4 vs 17.0 months; HR, 2.04; P = .043) and nitrosoureas (6.9 vs 8.0 months; HR, 1.63; P = .027), but not with bevacizumab (HR, 1.23; P = .60). In multivariable analyses, PTEN alteration remained associated with worse survival with regorafenib (HR, 1.88; P = .016) and nitrosoureas (HR, 1.97; P = .020). In the overall cohort, PTEN alteration remained associated with worse survival (HR, 2.04; 95% CI, 1.26-3.30; P = .0039), independently of MGMT promoter methylation. Conclusions PTEN alteration is a clinically relevant prognostic biomarker in recurrent IDH-wildtype glioblastoma and warrants prospective validation as a stratification factor.
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Authors Eugenia Cella, Maurizio Polano, Marta Padovan, Elena Maria Marchesani, Alberto Bosio, Luca Bertero, Marta Maccari, Giulia Cerretti, Mario Caccese, Martina Corrà, E. Bennicelli, Matteo Lambertini, Sara Lonardi, Roberta Rudà, Giuseppe Lombardi
Journal Neuro-Oncology Advances
Year 2026
DOI
10.1093/noajnl/vdag196
URL
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