THU617 Prolonged Exposure To Target Mitotane Concentrations Is Associated With Better Recurrence-free Survival In Patients With Adrenocortical Carcinoma On Adjuvant Treatment
Notice bibliographique
Résumé
Abstract Disclosure: S. Puglisi: None. A. Calabrese: None. V. Basile: None. O. Kimpel: Speaker; Self; HRA Pharmaceuticals. B. Altieri: None. A. Angelousi: None. G. Kaltsas: None. U. Ambroziak: None. M.L. Appetecchia: None. M. Arosio: None. A. Berruti: Advisory Board Member; Self; HRA Pharmaceuticals. D. Cosentini: None. L. Canu: None. F. Ceccato: None. G. Di Dalmazi: None. L. Bouys: None. R. Libè: None. K. Nowak: None. L. Papierska: None. J. Pittaway: None. T. Kienitz: None. M. Quinkler: None. Y. Elhassan: None. C. Ronchi: None. L. Saiegh: None. A. Stigliano: None. T. Dusek: None. D. Kastelan: None. M. Fassnacht: None. M. Terzolo: Advisory Board Member; Self; HRA Pharmaceuticals. Grant Recipient; Self; HRA Pharmaceuticals. Background: The management of adjuvant mitotane therapy in patients with adrenocortical carcinoma (ACC) is challenging. Plasma mitotane concentrations >14 mg/L have been associated with efficacy in the treatment of advanced ACC; however, data in the adjuvant setting are mixed. Moreover, there is no consensus on how to assess the optimal exposure to mitotane and all the proposed methods have inherent limitations. We have recently proposed a new method analogous to what is established for the anticoagulant warfarin, the time in target range (TTR). We aimed to evaluate whether the TTR is a factor influencing recurrence-free survival (RFS) in patients with ACC on adjuvant mitotane. Methods: This is an international, retrospective, cohort study undertaken in 18 centers in 8 countries, under the auspices of the European Network for the Study of Adrenal Tumors (ENSAT), including adult patients with ACC treated with adjuvant mitotane for at least 1 year following tumor resection, with the availability of at least 3 mitotane measurements per year. TTR was calculated with the Rosendaal method and expressed as the number of months with plasma mitotane concentration >14 mg/L. The following potential predictive factors for RFS have been investigated: patient sex and age, ENSAT stage, hormone secretion, resection status, Weiss score, Ki67 index, and TTR. Data are expressed as median and interquartile range. Results: From a total of 254 patients, 157 fulfilled inclusion criteria and were analyzed (F/M 94/63; age 49, 41-58 years), with a follow-up of 49 (33-92) months. The key baseline features were: 7.0% stage I, 69.4% II, 22.3% III, 1.3% IV; 51.6% secreting tumors; 87.2% R0, 2.6% R1, 10.2% RX; Weiss score 5 (4-7); Ki67 index 11 (5-20). All patients were treated with mitotane for 25 (22-36) months, with a TTR of 14 (6-21) months. At multivariate analysis, Ki67 index (HR 1.07, 95%CI, 1.02-1.12; p<0.01) and Weiss score (HR 1.7, 95%CI, 1.16-2.47; p<0.01) were associated with an increased risk of recurrence, while female sex (HR 0.14, 95%CI, 0.04-0.58; p<0.01) and TTR (HR 0.80, 95%CI, 0.70-0.90; p<0.001) were associated with a reduced risk. Conclusions The present findings show that the patients who are exposed to plasma mitotane >14 mg/L for longer periods have better RFS. These findings provide indirect evidence of the value of adjuvant therapy with mitotane and support the importance of drug monitoring to guide dose adjustment in clinical practice and improve patient outcome. Presentation: Thursday, June 15, 2023
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 distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| 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 | 0,000 | 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) | 0,000 | 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 tête enseignante, 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 ».