Kathleen Dekeister1,2, Pierre-Adrien Bolze3,4, Michel Tod5, Rémi Tod5, Jérôme Massardier3,6, Jean-Pierre Lotz7, Touria Hajri3, Olivier Colomban5, Michael J Seckl8, Ray Osborne9, Gilles Freyer10,5, François Golfier5,3,4, Benoit You10,5,3. 1. Oncology Medical Department, CITOHL, Université Claude Bernard Lyon-1, Hospices Civils de Lyon, Lyon, France. kathleen.dekeister@gmail.com. 2. EMR 3738 Ciblage Thérapeutique en Oncologie, Faculté de Médecine Lyon-Sud, BP12, 69310, Pierre-Bénite Cedex, France. kathleen.dekeister@gmail.com. 3. French Trophoblastic Disease Reference, Hospices Civils de Lyon, Lyon, France. 4. Gynecology-Obstetrics Department, Centre Hospitalier Lyon-Sud, Pierre-Bénite, France. 5. EMR 3738 Ciblage Thérapeutique en Oncologie, Faculté de Médecine Lyon-Sud, BP12, 69310, Pierre-Bénite Cedex, France. 6. Gynecology-Obstetrics Department, Centre Hospitalier Femme Mère Enfant, Bron, France. 7. Oncology Medical Department, Groupe Hospitalier APHP, Sorbonne Université, Hôpital Tenon, Paris, France. 8. Charing Cross Gestational Trophoblastic Disease Centre, Charing Cross Hospital Campus of Imperial College London, London, W68RF, UK. 9. Gynecology-Obstetrics Department, Sunnybrook Health Sciences Centre, Toronto, Canada. 10. Oncology Medical Department, CITOHL, Université Claude Bernard Lyon-1, Hospices Civils de Lyon, Lyon, France.
Abstract
PURPOSE: In a low-risk gestational trophoblastic neoplasia (GTN) treated with methotrexate (MTX), the modeled hCG (human chorionic gonadotropin) residual concentration (hCGres), calculated with NONMEM program® (NM) during the first 50 treatment days, is a predictor of MTX-resistance risk. This model was implemented with another algorithm on https://www.biomarker-kinetics.org/hCG . The objective was to confirm the validity of the website estimations with respect to NM. METHODS: The consistencies of modeled hCGres estimated by NM and by the website were assessed in a dataset of 60 fictive patients with simulated hCG profiles, as well as in an independent database of 531 actual patients. Moreover, the hCGres predictive values regarding MTX failure-risk were assessed. RESULTS: The values of hCGres obtained with both methods were highly consistent in the fictive patient and in the actual patient datasets: median relative prediction errors (RPE) were - 0.059 and 9.9 × 10-7, respectively. The ROC AUCs for predictions of MTX failure-risk were 0.90 (95% CI 0.87,0.93) with both NM and the website. The gradual association between increasing hCGres and the 2-year MTX failure-free survival was confirmed. CONCLUSION: There is a high consistency of hCGres estimates obtained with the two methods. The website is meant to help clinicians in the interpretation of hCG decline curves of MTX-treated GTN patients. hCGres is now validated for more than 1690 patients in four independent datasets, and its recognition as an early predictor of MTX resistance for treatment adjustment and for the future studies should be considered.
PURPOSE: In a low-risk gestational trophoblastic neoplasia (GTN) treated with methotrexate (MTX), the modeled hCG (human chorionic gonadotropin) residual concentration (hCGres), calculated with NONMEM program® (NM) during the first 50 treatment days, is a predictor of MTX-resistance risk. This model was implemented with another algorithm on https://www.biomarker-kinetics.org/hCG . The objective was to confirm the validity of the website estimations with respect to NM. METHODS: The consistencies of modeled hCGres estimated by NM and by the website were assessed in a dataset of 60 fictive patients with simulated hCG profiles, as well as in an independent database of 531 actual patients. Moreover, the hCGres predictive values regarding MTX failure-risk were assessed. RESULTS: The values of hCGres obtained with both methods were highly consistent in the fictive patient and in the actual patient datasets: median relative prediction errors (RPE) were - 0.059 and 9.9 × 10-7, respectively. The ROC AUCs for predictions of MTX failure-risk were 0.90 (95% CI 0.87,0.93) with both NM and the website. The gradual association between increasing hCGres and the 2-year MTX failure-free survival was confirmed. CONCLUSION: There is a high consistency of hCGres estimates obtained with the two methods. The website is meant to help clinicians in the interpretation of hCG decline curves of MTX-treated GTN patients. hCGres is now validated for more than 1690 patients in four independent datasets, and its recognition as an early predictor of MTX resistance for treatment adjustment and for the future studies should be considered.
Entities:
Keywords:
Algorithms; Chorionic gonadotropin; Drug resistance; Gestational trophoblastic disease; Neoplasm; Online systems
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