Population exposure-response model of 131I in patients with benign thyroid disease
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2021
Authors
Topić-Vučenović, ValentinaRajkovača, Zvezdana
Jelić, Dijana
Stanimirović, Dragi
Mikov, Momir
Miljković, Branislava
Vučićević, Katarina
Article (Published version)
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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 r...esponse-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.
Keywords:
Benign thyroid disorders / Biologically effective dose / Dose-rate effects / Outcome probability / Proportional odds model / Radioiodine therapySource:
European Journal of Pharmaceutical Sciences, 2021, 165Publisher:
- Elsevier B.V.
DOI: 10.1016/j.ejps.2021.105942
ISSN: 0928-0987
WoS: 000704184800001
Scopus: 2-s2.0-85110609435
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PharmacyTY - JOUR AU - Topić-Vučenović, Valentina AU - Rajkovača, Zvezdana AU - Jelić, Dijana AU - Stanimirović, Dragi AU - Mikov, Momir AU - Miljković, Branislava AU - Vučićević, Katarina PY - 2021 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3927 AB - 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. PB - Elsevier B.V. T2 - European Journal of Pharmaceutical Sciences T1 - Population exposure-response model of 131I in patients with benign thyroid disease VL - 165 DO - 10.1016/j.ejps.2021.105942 ER -
@article{ author = "Topić-Vučenović, Valentina and Rajkovača, Zvezdana and Jelić, Dijana and Stanimirović, Dragi and Mikov, Momir and Miljković, Branislava and Vučićević, Katarina", year = "2021", 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.", publisher = "Elsevier B.V.", journal = "European Journal of Pharmaceutical Sciences", title = "Population exposure-response model of 131I in patients with benign thyroid disease", volume = "165", doi = "10.1016/j.ejps.2021.105942" }
Topić-Vučenović, V., Rajkovača, Z., Jelić, D., Stanimirović, D., Mikov, M., Miljković, B.,& Vučićević, K.. (2021). Population exposure-response model of 131I in patients with benign thyroid disease. in European Journal of Pharmaceutical Sciences Elsevier B.V.., 165. https://doi.org/10.1016/j.ejps.2021.105942
Topić-Vučenović V, Rajkovača Z, Jelić D, Stanimirović D, Mikov M, Miljković B, Vučićević K. Population exposure-response model of 131I in patients with benign thyroid disease. in European Journal of Pharmaceutical Sciences. 2021;165. doi:10.1016/j.ejps.2021.105942 .
Topić-Vučenović, Valentina, Rajkovača, Zvezdana, Jelić, Dijana, Stanimirović, Dragi, Mikov, Momir, Miljković, Branislava, Vučićević, Katarina, "Population exposure-response model of 131I in patients with benign thyroid disease" in European Journal of Pharmaceutical Sciences, 165 (2021), https://doi.org/10.1016/j.ejps.2021.105942 . .