The influence of biologically effective dose (BED) on the 131I therapy response in patients with benign thyroid disease – nonlinear mixed effect modelling approach

Aim. The purpose of the study was to explore the influence of biologically effective dose (BED [Gy]), the administered radioactivity dose (Aa [MBq]), the total absorbed dose (ABD [Gy]), the maximum of absorbed dose-rate (MXR [Gy/h]) to radioactive iodine (131I) on the response in patients with benign thyroid disease.

Materials and methods. Data from adult patients with benign thyroid disease who had previously received a test dose of 131I activity were included in the analysis. Individual thyroid exposure parameters were estimated from the population biokinetic 131I model and the therapeutic activity doses (in range from 185 to 1300 MBq). Patients response was followed up at periodic intervals, starting from 4-6 weeks, up to one year after the administration of 131I. A successful clinical outcome was resolution of of hyperthyroidism. A population exposure-response analysis was performed using nonlinear mixed-effects modelling using NONMEM® (v. 7.4). The response data was modelled as ordered categorical with three levels (hyper-, eu- and hypothyroidism). The performance of the final model was evaluated using visual predictive check (VPC).

Results. In total 95 adult patients were analyzed, including 57 (60%) with Graves’ disease, 22 (23.2%) with toxic multinodular goiter and 16 (16.8%) with toxic adenoma. The probability of the outcome 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. Among all tested exposure measures, BED was included in the final model. Its inclusion in the base model was statistically significant (p<0.001). The value of 289.7 Gy was associated with 80% probability of successful treatment outcome one year after 131I application in patients with median thyroid volume of 32.28 mL.

Conclusion. The results indicate that using BED formalism could lead to a better individualisation of the therapy. The larger thyroid volume is associated with a lower probability of a successful outcome.


  1. Topic Vucenovic V, Rajkovaca Z, Jelic D, Stanimirovic D, Vuleta G, Miljkovic B, Vucicevic K. Investigation of factors influencing radioiodine ((131)I) biokinetics in patients with benign thyroid disease using nonlinear mixed effects approach. Eur J Clin Pharmacol. 2018;74(8):1037-1045.
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Katarina Vucicevic

  • Faculty of Pharmacy-University of Belgrade