Valentina Topić Vučenović1, Zvezdana Rajkovača2, Dijana Jelić3, Dragi Stanimirović2, Momir Mikov4, Branislava Miljković5, Katarina Vučićević5. 1. Department of Pharmacy, Faculty of Medicine, University of Banja Luka, Save Mrkalja 14, 78000 Banja Luka, Bosnia and Herzegovina; Department of Pharmacokinetics and Clinical Pharmacy, University of Belgrade - Faculty of Pharmacy, Vojvode Stepe 450, 11221 Belgrade, Republic of Serbia. Electronic address: valentina.topic.vucenovic@med.unibl.org. 2. Institute of Nuclear Medicine and Thyroid Gland Disease, University Clinical Centre of the Republic of Srpska, 12 beba bb, 78000 Banja Luka, Bosnia and Herzegovina. 3. Chemistry Department, Faculty of Natural Sciences and Mathematics, University of Banja Luka, Mladena Stojanovića 2, 78000 Banja Luka, Bosnia and Herzegovina. 4. Department of Pharmacology, Toxicology and Clinical Pharmacology, University of Novi Sad - Faculty of Medicine, Hajduk Veljkova 3, 21000 Novi Sad, Republic of Serbia. 5. Department of Pharmacokinetics and Clinical Pharmacy, University of Belgrade - Faculty of Pharmacy, Vojvode Stepe 450, 11221 Belgrade, Republic of Serbia.
Abstract
PURPOSE: The study aimed to explore the relationship of different exposure measures with 131I therapy response in patients with benign thyroid disease, estimate the variability in the response, investigate possible covariates, and discuss dosing implications of the results. METHODS: A population exposure-response analysis was performed using nonlinear mixed-effects modelling. Data from 95 adult patients with benign thyroid disease were analysed. Evaluated exposure parameters were: administered radioactivity dose (Aa) [MBq], total absorbed dose (ABD) [Gy], maximum of absorbed dose-rate (MXR) [Gy/h] and biologically effective dose (BED) [Gy]. The response was modelled as ordered categorical data: hyper-, eu- and hypothyroidism. The final model performance was evaluated by a visual predictive check. RESULTS: The probability of the outcome following 131I therapy was best described by a proportional-odds model, including the log-linear model of 131I effect and the exponential model of the response-time relationship. All exposure measures were statistically significant with p<0.001, with BED and ABD being statistically better than the other two. Nevertheless, as BED resulted in the lowest AIC value, it was included in the final model. Accordingly, BED value of 289.7 Gy is associated with 80% probability of successful treatment outcome 12 months after 131I application in patients with median thyroid volume (32.28 mL). The target thyroid volume was a statistically significant covariate. The visual predictive check of the final model showed good model performance. CONCLUSION: Our results imply that BED formalism could aid in therapy individualisation. The larger thyroid volume is associated with a lower probability of a successful outcome.
PURPOSE: The study aimed to explore the relationship of different exposure measures with 131I therapy response in patients with benign thyroid disease, estimate the variability in the response, investigate possible covariates, and discuss dosing implications of the results. METHODS: A population exposure-response analysis was performed using nonlinear mixed-effects modelling. Data from 95 adult patients with benign thyroid disease were analysed. Evaluated exposure parameters were: administered radioactivity dose (Aa) [MBq], total absorbed dose (ABD) [Gy], maximum of absorbed dose-rate (MXR) [Gy/h] and biologically effective dose (BED) [Gy]. The response was modelled as ordered categorical data: hyper-, eu- and hypothyroidism. The final model performance was evaluated by a visual predictive check. RESULTS: The probability of the outcome following 131I therapy was best described by a proportional-odds model, including the log-linear model of 131I effect and the exponential model of the response-time relationship. All exposure measures were statistically significant with p<0.001, with BED and ABD being statistically better than the other two. Nevertheless, as BED resulted in the lowest AIC value, it was included in the final model. Accordingly, BED value of 289.7 Gy is associated with 80% probability of successful treatment outcome 12 months after 131I application in patients with median thyroid volume (32.28 mL). The target thyroid volume was a statistically significant covariate. The visual predictive check of the final model showed good model performance. CONCLUSION: Our results imply that BED formalism could aid in therapy individualisation. The larger thyroid volume is associated with a lower probability of a successful outcome.
Authors: Christian Happel; Wolfgang Tilman Kranert; Benjamin Bockisch; Amir Sabet; Frank Grünwald; Daniel Groener Journal: Sci Rep Date: 2022-08-17 Impact factor: 4.996