Neuro-oncology advances · 2026
Prognostic impact of phosphatase and tensin homolog status in recurrent IDH-wildtype glioblastoma receiving second-line therapy.
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Cella Eugenia, Polano Maurizio, Padovan Marta, Marchesani Elena Maria, Bosio Alberto, Bertero Luca, Maccari Marta, Cerretti Giulia, Caccese Mario, Corrà Martina, Bennicelli Elisa, Lambertini Matteo, Lonardi Sara, Rudà Roberta, Lombardi Giuseppe
Аннотация
BACKGROUND: Recurrent IDH-wildtype glioblastoma has a poor prognosis, and no validated molecular biomarker guides second-line treatment choices. Because phosphatase and tensin homolog (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. Phosphatase and tensin homolog alterations were assessed by next generation sequencing. Overall survival (OS) 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; hazard ratio [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% confidence interval, 1.26-3.30; P = .0039), independently of O⁶-methylguanine-DNA methyltransferase promoter methylation.
CONCLUSIONS: Phosphatase and tensin homolog alteration is a clinically relevant prognostic biomarker in recurrent IDH-wildtype glioblastoma and warrants prospective validation as a stratification factor.
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. Phosphatase and tensin homolog alterations were assessed by next generation sequencing. Overall survival (OS) 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; hazard ratio [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% confidence interval, 1.26-3.30; P = .0039), independently of O⁶-methylguanine-DNA methyltransferase promoter methylation.
CONCLUSIONS: Phosphatase and tensin homolog alteration is a clinically relevant prognostic biomarker in recurrent IDH-wildtype glioblastoma and warrants prospective validation as a stratification factor.