PD44-02 PHARMACOGENOMIC DETERMINANTS OF SERUM STEROID HORMONE RESPONSES TO ABIRATERONE OR ENZALUTAMIDE AND HSD3B1 GENE MUTATION IN CRPC PATIENTS
Notice bibliographique
Résumé
You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology II (PD44)1 Sep 2021PD44-02 PHARMACOGENOMIC DETERMINANTS OF SERUM STEROID HORMONE RESPONSES TO ABIRATERONE OR ENZALUTAMIDE AND HSD3B1 GENE MUTATION IN CRPC PATIENTS Hosam Serag, Emilia Chen, Hans Adomat, Daniel Khalaf, Alexander Wyatt, and Martin Gleave Hosam SeragHosam Serag More articles by this author , Emilia ChenEmilia Chen More articles by this author , Hans AdomatHans Adomat More articles by this author , Daniel KhalafDaniel Khalaf More articles by this author , Alexander WyattAlexander Wyatt More articles by this author , and Martin GleaveMartin Gleave More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002058.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Abiraterone and enzalutamide are commonly used for treating patients with castration-resistant prostate cancer (CRPC). Serum levels of steroid hormones can be affected by drug type and mutation in the gene HSD3B1, with potential implications for outcome prediction. Objective: To determine the impact of treatment with abiraterone or enzalutamide as well as HSD3B1 gene mutation on steroid hormones, quantified by mass spectrometry (MS) in patients with CRPC. METHODS: A multicentre, randomised, crossover trial was performed in six cancer centres in British Columbia, Canada. Adult patients with metastatic CRPC were included. In this study we performed retrospective steroid MS analysis from patients in both arms of the trial.Patients were randomly assigned to groups A and B (1:1). Group A received Abiraterone acetate until PSA progression, followed by crossover to Enzalutamide. Group B followed the opposite sequence. Primary outcomes included levels of testosterone (T), dihydrotestosterone (DHT), dehydroepiandrosterone (DHEA), androstenedione, and progesterone at baseline, before crossover, and at the end of therapy (EOT) as well as variants of HSD3B1 allele. RESULTS: Baseline serum levels of T, DHT, DHEA, androstenedione, and progesterone were similar between the two arms. On crossover, the levels of T, DHT, DHEA, and androstenedione significantly decreased, while progesterone level significantly increased, in the abiraterone arm compared to the enzalutamide arm. This is reversed after patient cross-over (Figure 1). No significant association was detected in the levels of steroid hormones between HSD3B1 (1245 A) and HSD3B1 (1245 A>C) genotypes either at baseline, or after exposure to either treatment (Figure 2). The sample size was relatively small for assessing effect of HSD3B1 mutations. CONCLUSIONS: The results confirm expected effects of abiraterone and enzalutamide on steroid hormones levels in CRPC patients. HSD3B1 mutation seems not to affect levels of steroid hormones. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e736-e737 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Hosam Serag More articles by this author Emilia Chen More articles by this author Hans Adomat More articles by this author Daniel Khalaf More articles by this author Alexander Wyatt More articles by this author Martin Gleave More articles by this author Expand All Advertisement Loading ...
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 | 0,000 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,008 | 0,001 |
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 ».