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@ARTICLE{LeRhun:306583,
      author       = {E. Le Rhun and D. Sain and S. C. Erridge and D. A. Reardon
                      and G. Minniti and P. Roth and W. Wick$^*$ and B. Nabors and
                      J. Sampson and W. Mason and T. Cloughesy and J. C.
                      Reijneveld and R. Stupp and M. Preusser and T. Gorlia and M.
                      Weller},
      title        = {{P}roton {P}ump {I}nhibitor {U}se and {S}urvival in
                      {P}atients {W}ith {N}ewly {D}iagnosed {G}lioblastoma.},
      journal      = {JAMA network open},
      volume       = {8},
      number       = {11},
      issn         = {2574-3805},
      address      = {Chicago, Ill.},
      publisher    = {American Medical Association},
      reportid     = {DKFZ-2025-02624},
      pages        = {e2545578 -},
      year         = {2025},
      abstract     = {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.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.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.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).The primary outcome measures were
                      progression-free survival (PFS) and overall survival (OS)
                      from baseline and from the start of each corresponding
                      landmark time.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 MGMT 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 MGMT promoter methylation and steroid
                      use.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. .},
      keywords     = {Humans / Glioblastoma: mortality / Glioblastoma: drug
                      therapy / Proton Pump Inhibitors: therapeutic use / Male /
                      Female / Middle Aged / Aged / Adult / Brain Neoplasms:
                      mortality / Brain Neoplasms: drug therapy / Temozolomide:
                      therapeutic use / Proton Pump Inhibitors (NLM Chemicals) /
                      Temozolomide (NLM Chemicals)},
      cin          = {B320 / HD01},
      ddc          = {610},
      cid          = {I:(DE-He78)B320-20160331 / I:(DE-He78)HD01-20160331},
      pnm          = {312 - Funktionelle und strukturelle Genomforschung
                      (POF4-312)},
      pid          = {G:(DE-HGF)POF4-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41288972},
      doi          = {10.1001/jamanetworkopen.2025.45578},
      url          = {https://inrepo02.dkfz.de/record/306583},
}