Effects on bone resorption markers of continuing pamidronate or switching to zoledronic acid in patients with high risk bone metastases from breast cancer
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
BACKGROUND: Switching patients who remain at high risk of skeletal related events (SREs) despite pamidronate to the more potent bisphosphonate zoledronate, may be an effective treatment strategy. As part of a previously reported clinic study in this setting, we evaluated whether biomarkers for bone resorption, such as Bone-Specific Alkaline Phosphatase (BSAP), bone sialoprotein (BSP), and N-terminal telopeptide (NTX) correlated with subsequent SRE risk. METHODS: Breast cancer patients who remained at high risk of SREs despite at least 3 months of q.3-4 weekly pamidronate were randomized to either continue on pamidronate or to switch to zoledronate (4 mg) once every 4 weeks for 12-weeks. High risk bone metastases were defined by either: occurrence of a prior SRE, bone pain, radiologic progression of bone metastases and/or serum C-terminal telopeptide (CTx) levels > 400 ng/L despite pamidronate use. Serum samples were collected at baseline and weeks 1, 4, 8 and 12 (CTx and BSAP) and baseline and week 12 (NTx and BSP), and all putative biomarkers were measured by ELISA. Follow up was extended to 2 years post trial entry for risk of subsequent SREs. The Kaplan-Meier method was used to estimate time-to-event outcomes. Generalized estimating equations (GEE) were used to evaluate if laboratory values over time or the change in laboratory values from baseline were associated with having a SRE within the time frame of this study. RESULTS: From March 2012 to May 2014, 76 patients were screened, with 73 eligible for enrolment. All 73 patients were available for biochemical analysis, with 35 patients receiving pamidronate and 38 patients receiving zoledronate. The GEE analysis found that no laboratory value was associated with having a subsequent SRE. Interaction between visit and laboratory values was also investigated, but no interaction effect was statistically significant. Only increased number of lines of prior hormonal treatment was associated with subsequent SRE risk. CONCLUSION: Our analysis failed to find any association between serum BSAP, BSP, CTx or NTx levels and subsequent SRE risk in this cohort of patients. This lack of correlation between serum biomarkers and clinical outcomes could be due to influences of prior bisphosphonate treatment or presence of extra-osseous metastases in a significant proportion of enrolled patients. As such, caution should be used in biomarker interpretation and use to direct decision making regarding SRE risk for high risk patients in this setting.
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.
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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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 | 0.001 |
| 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 it