Exploratory analysis of angiotensin converting enzyme (ACE) and aldosterone (Ald) serum levels as prognostic and predictive biomarkers on the NCIC CTG BR24 trial.
Bibliographic record
Abstract
8048 Background: Benefit from angiogenesis inhibitors (AI) has been linked to high blood pressure. One of the main determinants of blood pressure is the renin-angiotensin axis. We undertook an exploratory, retrospective analysis of ACE and Ald serum levels on specimens banked during the conduct of the BR24 study. The aim was to evaluate these markers for their prognostic significance and their predictive value regarding Cediranib (Ced) treatment. Methods: The NCIC CTG BR24 study randomized advanced non-small cell lung cancer patients (pts) to carboplatin and paclitaxel (CP) +/- Ced. ACE and Ald serum levels were retrospectively tested on baseline samples using commercial ELISA kits. A graphic method, differentiating treatment effect by the range of marker, was used to determine cutoff points (JCO 2010, 28: 5247). Exploratory analyses were performed to correlate biomarkers levels with pts characteristics and overall survival (OS). Association between categorical variables was assessed by Chi-square test or Fisher’s exact test; time to event correlation with biomarkers was tested using a Cox regression model. Potential confounding factors including medications were integrated into the statistical model. Results: Biomarker data was available in 226 of 296 randomized pts. The tested pts vs. all the randomized pts were more likely to have a lower performance status (PS, p=0.03), a normal LDH (p=0.05) and to be ever-smokers (p=0.015). The determined cutoffs were ACE: 115ng/ml and Ald: 250 pg/ml. High ACE was associated with a better PS (p=0.03). High ACE levels were prognostic for longer OS (adjusted HR 0.52 [95%C.I. 0.29-0.92], p=0.025). High ACE pts had no OS benefit (HR 1.27 [95% C.I. 0.78–2.08], p=0.34), while low ACE predicted OS benefit from the addition of Ced to CP (HR 0.64 [95%CI 0.42-0.97], p=0.03). Interaction p value=0.03; this remained significant after adjustment in multivariate analyses. Ald levels were neither prognostic nor predictive. Conclusions: This exploratory analysis suggests high ACE serum levels maybe prognostic for better OS, while low ACE may predict benefit from Ced when added to CP.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.007 | 0.007 |
| Meta-epidemiology (narrow) | 0.002 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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 source (direct Gemma or distilled Codex), 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".