Abstract A072: Serum sex steroids as prognostic biomarkers in patients receiving androgen-deprivation therapy for recurrent prostate cancer post-radiotherapy: A post hoc analysis of the PR.7 trial
Notice bibliographique
Résumé
Abstract Background and Objective: Nadir testosterone values following initiation of androgen deprivation therapy have been shown in several studies to be prognostic for outcome, including time to castration-resistant prostate cancer (TTCRPC) and cancer specific survival (CSS). The biologic reasons for this remain unclear. Using cryopreserved serum from the PR.7 trial of intermittent vs. continuous androgen deprivation therapy(ADT), we determined to assess the role of related sex steroids as prognostic biomarkers in men on androgen deprivation therapy for recurrent cancer post-radiotherapy. Patients and Methods: Canadian patients in the PR.7 trial randomized to the continuous arm were included. Patients were excluded who did not receive ADT(n=3), had <2 years of follow-up (n=2), received exogenous estrogens or glucocorticoids(n=5), or samples were unavailable(n=36). LC-MS/MS was performed using a validated method to simultaneously analyze ten steroids: dehydroepiandrosterone (DHEA), testosterone (T), dihydrotestosterone (DHT), androst-5-ene-β,17β-diol (5-diol), androstenedione (4-dione), androsterone (AD), estrone (E1), estradiol (E2), progesterone, and androstane-3β,17β-diol (3βdiol). Descriptive statistics and correlation analyses were performed, with longitudinal changes categorized as stable, increasing, decreasing, or mixed. The prognostic value of individual steroid tertiles as well as E1:E2, E2:T, and DHT:T ratios were assessed by Kaplan-Meier analysis and Cox proportional hazards adjusted for baseline clinical variables. Outcomes assessed were TTCRPC, CSS, and overall survival (OS). Results: A total of 219 patients were included in the analysis who had a cryopreserved serum available within 2 years of randomization, with 104 patients having 2 subsequent annual samples available for measurement. Values for DHT, T, 4-dione, AD, DHEA, and 5-diol tended to be correlated among samples. Lower DHEA and AD values were significant associated with older age as was lower DHEA and DHT values with poorer performance status. Higher tertiles of E1 and E2 were associated with sooner TTCRP (log-rank, p=0.03, p=0.02, respectively). Similar trends were seen for 4-dione in predicting TTCRPC (log-rank, p=0.07). Upon adjustment, the highest tertile of E2:T had increased hazard ratios (HR) for CSS (HR=2.36, 95% CI I: 0.90-6.21; p=0.08) and TTCRPC (HR=1.70, 95% CI: 0.90-3.23; p=0.10) relative to the lowest tertile. In an analysis of the subset of patients with longitudinal values, increasing levels of AD over time were associated with poorer CSS and OS (log-rank: p=0.04 and p <0.01, respectively). On adjusted analysis, increasing AD levels had a HR for CSS of 3.43 (95% CI: 0.63-18.67; p=0.15) and a HR for OS of 4.75 (95% CI: 1.49-15.17; p <0.01). Limitations include the number of events for some groups. Conclusions: Increased levels of E1, E2, and AD during ADT correlated with adverse TTCRPC and CSS. Serum sex steroids, including both androgens and estrogens, may act as prognostic biomarkers in men receiving ADT for recurrent prostate cancer. Further investigation is warranted to support clinical use. Citation Format: Paul Toren, Azik Hoffman, Keyue Ding, France-Hélène Joncas, Frédéric Pouliot, Yves Fradet, Éric Lévesque, Chantal Guillemette, Laurence Klotz. Serum sex steroids as prognostic biomarkers in patients receiving androgen-deprivation therapy for recurrent prostate cancer post-radiotherapy: A post hoc analysis of the PR.7 trial [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr A072.
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 | 0,004 | 0,003 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,003 | 0,003 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,002 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,004 | 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 ».