{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T14:01:04Z","timestamp":1793628064589,"version":"4.5.1"},"reference-count":32,"publisher":"American Medical Association (AMA)","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"\n Importance<\/jats:title>\n Proton pump inhibitors (PPI) are often prescribed to prevent steroid-induced gastritis and peptic ulcer disease in patients with glioblastoma. Yet, these drugs may enhance the activity of aldehyde dehydrogenase 1 A1 (ALDH1A1), which has been linked to protection from oxidative stress, radiotherapy, and chemotherapy.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To explore the associations of the use of potent ALDH1A1-activating PPIs (PA-PPIs) and other antacid drugs with outcomes in patients with newly diagnosed glioblastoma.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This meta-analysis was a secondary analysis of individual prospectively captured patient data using a dataset of 5 randomized clinical trials conducted between 2008 and 2020. Participants included patients with a new diagnosis of glioblastoma. Data analysis was completed in November 2024.<\/jats:p>\n <\/jats:sec>\n \n Exposure<\/jats:title>\n We assessed drug use at baseline and defined 3 landmarks: start of temozolomide maintenance cycles 1 (landmark 1) and 4 (landmark 2), and end of cycle 6 (landmark 3).<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n The primary outcome measures were progression-free survival (PFS) and overall survival (OS) from baseline and from the start of each corresponding landmark time.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The study population included 2981 patients (1858 [62.3%] male; median [range] age, 58 [18-85] years). On univariate analysis, patients treated with PA-PPI had worse PFS and OS at all 4 time points. The multivariate analysis accounting for age, sex, performance status, steroid use, extent of resection, and\n MGMT<\/jats:italic>\n status confirmed a difference for PFS at landmarks 1 (hazard ratio [HR], 1.14 [95% CI, 1.01-1.28]), 2 (HR, 1.26 [95% CI, 1.09-1.44]), and 3 (HR, 1.31 [95% CI, 1.10-1.56]), and for OS at landmarks 1 (HR, 1.34 [95% CI, 1.08-1.66]) and 2 (HR, 1.14 [95% CI, 1.01-1.29]). No such association was seen for the use of other antacid drugs. The negative association of PA-PPI use with PFS and OS was observed independently of\n MGMT<\/jats:italic>\n promoter methylation and steroid use.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n In this meta-analysis of patients with newly diagnosed glioblastoma, PPI use was associated with inferior survival outcomes. These findings suggest that PA-PPI use should be discouraged in patients with glioblastoma, since alternative agents are available and a detrimental effect cannot be excluded. Translational research studies should explore whether PPI-induced activity of ALDH mediates the potential adverse effects of PPI in glioblastoma.<\/jats:p>\n .<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2025.45578","type":"journal-article","created":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T16:00:47Z","timestamp":1764086447000},"page":"e2545578","source":"Crossref","is-referenced-by-count":3,"title":["Proton Pump Inhibitor Use and Survival in Patients With Newly Diagnosed Glioblastoma"],"prefix":"10.1001","volume":"8","author":[{"given":"Emilie","family":"Le Rhun","sequence":"first","affiliation":[{"name":"Department of Medical Oncology and Hematology, University Hospital and University of Zurich, Zurich, Switzerland"},{"name":"Department of Neurology, University Hospital and University of Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debaleena","family":"Sain","sequence":"additional","affiliation":[{"name":"European Organisation for Research and Treatment of Cancer Headquarters, Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara C.","family":"Erridge","sequence":"additional","affiliation":[{"name":"Edinburgh Cancer Centre, University of Edinburgh, Edinburgh, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Reardon","sequence":"additional","affiliation":[{"name":"Center for Neuro-Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Minniti","sequence":"additional","affiliation":[{"name":"Department of Radiological Sciences, Oncology and Anatomical Pathology, Sapienza University of Rome, Rome, Italy"},{"name":"Policlinico Umberto I, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Roth","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Hospital and University of Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Wick","sequence":"additional","affiliation":[{"name":"Department of Neurology and European Center for Neurooncology, University Hospital Heidelberg, Heidelberg University, Heidelberg, Germany"},{"name":"Clinical Cooperation Unit Neuro-Oncology, German Cancer Research Center and German Consortium for Translational Cancer Research, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Burt","family":"Nabors","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Alabama at Birmingham, Birmingham"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Sampson","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Duke University Medical Center, Preston Robert Tisch Brain Tumor Center at Duke, Durham, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Warren","family":"Mason","sequence":"additional","affiliation":[{"name":"Department of Medicine, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Cloughesy","sequence":"additional","affiliation":[{"name":"Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob C.","family":"Reijneveld","sequence":"additional","affiliation":[{"name":"Department of Neurology & Brain Tumor Center Amsterdam, Amsterdam University Medical Center, Amsterdam, the Netherlands"},{"name":"Department of Neurology, Stichting Epilepsie Instellingen Nederland, Heemstede, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger","family":"Stupp","sequence":"additional","affiliation":[{"name":"Lou and Jean Malnati Brain Tumor Institute, Robert H. 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