Bone metabolism biomarkers in men with advanced prostate cancer (PC) and bone metastases treated with denosumab versus zoledronic acid (ZA).
Bibliographic record
Abstract
267 Background: Denosumab, compared with ZA, has recently demonstrated significant benefits in preventing skeletal-related events (SREs) in a double-blind phase 3 study of men with castration-resistant PC and bone metastases (N=1901). This post hoc analysis was performed to determine if key bone metabolism biomarker levels correlated with time-to-first SRE. Methods: Time-to-Grade ≥2 increase in total serum alkaline phosphatase (ALP) was assessed for correlation with time-to-first SRE. Levels of urinary N-telopeptide (uNTX) and serum bone-specific alkaline phosphatase (BSAP) markers were measured at baseline and study week 13, and correlations with time-to-first SRE were assessed. Covariate analyses were performed using a Cox proportional hazards model, stratified by treatment group or (for baseline analyses) with treatment group as the independent variable. Results: Analysis of the relationship between time-to-Grade ≥2 increase in total ALP and time-to-first SRE demonstrated that Grade ≥2 increases in ALP of PC patients were associated with a higher risk of first SRE (hazard ratio [HR] 1.838, 95% confidence interval [CI] 1.559, 2.167; P<0.0001). In dichotomized analyses (< vs ≥ median), a higher level of uNTX and BSAP (at baseline or week 13) was correlated with an increased risk of first SRE (Table). In baseline covariate analyses, treatment benefit for denosumab was maintained after adjusting for either baseline uNTX (HR 0.818, 95% CI 0.703, 0.951; P=0.0091) or BSAP (HR 0.813, 95% CI 0.700, 0.943; P=0.0061). Conclusions: Higher levels of uNTX or BSAP at baseline or week 13 were associated with worse SRE outcomes in men with advanced PC and bone metastases. Denosumab was more efficacious for preventing or delaying SREs compared with ZA, regardless of bone-related biomarker levels. Relationship of covariate to time-to-first SRE Clinical trial information: NCT00321620. [Table: see text]
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".