{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T17:26:34Z","timestamp":1787073994700,"version":"build-2736575974"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"content-version":"vor","delay-in-days":207,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health through the \u2018Ricerca Corrente 2026\u2019","award":["CDC099183"],"award-info":[{"award-number":["CDC099183"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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 O\u2076-methylguanine-DNA methyltransferase promoter methylation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Phosphatase and tensin homolog alteration is a clinically relevant prognostic biomarker in recurrent IDH-wildtype glioblastoma and warrants prospective validation as a stratification factor.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/noajnl\/vdag196","type":"journal-article","created":{"date-parts":[[2026,7,26]],"date-time":"2026-07-26T11:30:58Z","timestamp":1785065458000},"source":"Crossref","is-referenced-by-count":0,"title":["Prognostic impact of phosphatase and tensin homolog status in recurrent IDH-wildtype glioblastoma receiving second-line therapy"],"prefix":"10.1093","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-9507-8357","authenticated-orcid":false,"given":"Eugenia","family":"Cella","sequence":"first","affiliation":[{"name":"Department of Internal Medicine and Medical Specialties (DIMI), School of Medicine, University of Genova , Genova,","place":["Italy"]},{"name":"Department of Oncology, San Paolo Hospital , Savona,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Polano","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Pharmacology Unit, National Cancer Institute C.R.O.-IRCCS Aviano , Aviano,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7362-3127","authenticated-orcid":false,"given":"Marta","family":"Padovan","sequence":"additional","affiliation":[{"name":"Department of Oncology, Oncology 1, Veneto Institute of Oncology IOV-IRCCS , Padova,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena Maria","family":"Marchesani","sequence":"additional","affiliation":[{"name":"Department of Neuroscience \u201cRita Levi Montalcini\u201d, Division of Neuro-Oncology, University of Turin , Turin,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Bosio","sequence":"additional","affiliation":[{"name":"Department of Oncology, Oncology 1, Veneto Institute of Oncology IOV-IRCCS , Padova,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9887-7668","authenticated-orcid":false,"given":"Luca","family":"Bertero","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Pathology Unit, University of Turin and Citt\u00e0 della Salute e della Scienza University Hospital , Turin,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Maccari","sequence":"additional","affiliation":[{"name":"Department of Oncology, Oncology 1, Veneto Institute of Oncology IOV-IRCCS , Padova,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Cerretti","sequence":"additional","affiliation":[{"name":"Department of Oncology, Oncology 1, Veneto Institute of Oncology IOV-IRCCS , Padova,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Caccese","sequence":"additional","affiliation":[{"name":"Department of Oncology, Oncology 1, Veneto Institute of Oncology IOV-IRCCS , Padova,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Corr\u00e0","sequence":"additional","affiliation":[{"name":"Department of Oncology, Oncology 1, Veneto Institute of Oncology IOV-IRCCS , Padova,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Bennicelli","sequence":"additional","affiliation":[{"name":"Department of Oncology, Academic Oncology Unit, IRCCS Azienda Ospedaliera Metropolitana , Genova,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1797-5296","authenticated-orcid":false,"given":"Matteo","family":"Lambertini","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Medical Specialties (DIMI), School of Medicine, University of Genova , Genova,","place":["Italy"]},{"name":"Academic Medical Oncology Unit, Ente Ospedaliero Ospedali Galliera , Genova,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Lonardi","sequence":"additional","affiliation":[{"name":"Department of Oncology, Oncology 1, Veneto Institute of Oncology IOV-IRCCS , 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