P17.15.A ASSOCIATION OF PROTON PUMP INHIBITOR USE WITH OUTCOME OF PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA
Bibliographic record
Abstract
Abstract BACKGROUND 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. MATERIAL AND METHODS We analyzed data from 2981 patients enrolled into 5 randomized clinical trials for newly diagnosed glioblastoma to explore an association of the use of potent ALDH1A1-activating PPI (PA-PPI) and other anti-acid drugs with outcome. We assessed drug use at baseline and at defined landmarks: start of temozolomide maintenance cycles 1 (landmark 1) and 4 (landmark 2), and end of cycle 6 (landmark 3). RESULTS On univariate analysis, we noted inferior progression-free and overall survival for patients treated with PA-PPI at all 4 time points. The multivariate analysis accounting for age, sex, performance status, steroid use, extent of resection, and O6-methylguanine DNA methyltransferase promoter methylation (MGMT) status confirmed a difference for progression-free survival at landmarks 1, 2 and 3, and for overall survival at landmarks 1 and 2. No such effect was seen for the use of other anti-acid drugs. The negative association of PA-PPI use with outcome was observed independently of MGMT promoter methylation and of steroid use. CONCLUSION We conclude that PA-PPI use should be discouraged in patients with glioblastoma since alternative agents are available and since 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.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".