Abstract P2-05-12: Effects of de-escalated bisphosphonate therapy on bone turnover or metastasis markers and their correlation with risk of skeletal related events – A biomarker analysis in conjunction with the REFORM study.
Notice bibliographique
Résumé
Abstract Background: Despite variability in an individual's risk of skeletal related events (SREs) from bone metastases (BM), all patients are treated using a similar dose and schedule (q3-4 wk) of IV bisphosphonate (BP). The REFORM trial (Amir et al., Am J Clin Oncol, in press) was a pilot randomised study evaluating the efficacy of de-escalated (q12 wk) versus standard (q3-4 wk) pamidronate in maintaining C-telopeptide (CTx) levels in the low risk range (<600ng/L) in patients with BM from breast cancer. Here we report a biomarker substudy, where additional biomarkers of bone turnover and BM behaviour were measured and correlated with SRE risk. Methods: Eligible patients with BM, who had received ≥ 3 months of q3-4 wk IV BP and no systemic treatment change within 4 wks of study entry were enrolled. Serum & urine obtained at baseline and at 12 wks were assessed for urinary N-telopeptide (uNTx), serum procollagen type I amino-terminal propeptide (P1NP), transforming growth factor (TGF)-β, activinA and bone sialoprotein (BSP) by ELISA. Levels were correlated with number of SREs using linear regression analysis. Changes in biomarkers from baseline to 12 wks were used to calculate odds ratios for coming off study (due to either elevated CTx or SRE) or having an SRE alone using logistic regression analysis. Results: REFORM randomized 19 patients to each treatment arm, and found that the SRE rate at 1 year in both arms was the same (n = 2). Although the mean level of the standard bone turnover marker CTx decreased slightly from baseline to wk 12 in the q3-4 wk group (240±50ng/L to 206±46ng/L), and slightly increased in the q12 wk treated group (263±65ng/L to 313±71ng/L), these changes were not statistically significant (p = 0.8). Mean activinA levels were slightly increased in both treatment arms from baseline to wk 12 (730±93pg/ml to 875±148pg/ml in q3-4 wk group vs 445±35pg/ml to 582±61pg/ml in q12 wk group) but did not quite reach statistical significance (p = 0.1). Levels of TGF-β from baseline to 12 wks in both groups was similar (22±1.6ng/ml to 22±2.3ng/ml for q3-4 wk vs 23±2.2ng/ml to 24±2.4ng/ml for q12 wk group, p = 0.8). Although the number of SREs was small, mean CTx levels at wk 12 were statistically different between patients who experienced SREs vs those that did not (615±72ng/L, n=4 vs 190±26ng/L, n=19, p < 0.0001). Although it did not reach statistical significance, mean activinA levels at wk 12 were also higher in patients who had SREs than those that did not (1069±358pg/ml, n=3 vs 681±83pg/ml, n=18, p = 0.12). Results of NTx, BSP and P1NP and correlations with more mature clinical data will also be presented. Conclusions: In patients with BM from breast cancer with low levels of bone resorption markers, CTx predicted and activinA trended to predict SRE risk. However the non-significant trends in increasing CTx in de-escalated BP treatment, together with the observation that activinA levels are similar regardless of dosing regimen, suggest that analysis of conventional and experimental biomarkers of SRE risk requires further examination in other larger patient cohorts comparing de-escalated therapy. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-05-12.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,002 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».