THU617 Prolonged Exposure To Target Mitotane Concentrations Is Associated With Better Recurrence-free Survival In Patients With Adrenocortical Carcinoma On Adjuvant Treatment
Bibliographic record
Abstract
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
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How this classification was reachedexpand
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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".