Normal tissue complication probability models of hypothyroidism after radiotherapy for breast cancer.

Purpose: We aimed to develop Lyman-Kutcher-Burman (LKB) and multivariable normal tissue complication probability (NTCP) models to predict the risk of radiation-induced hypothyroidism (RIHT) in breast cancer patients.

Materials And Methods: A total of 1,063 breast cancer patients who underwent whole breast irradiation between 2009 and 2016 were analyzed. Individual dose-volume histograms were used to generate LKB and multivariable logistic regression models. LKB model was fit using the thyroid radiation dose-volume parameters. A multivariable model was constructed to identify potential dosimetric and clinical parameters associated with RIHT. Internal validation was conducted using bootstrapping techniques, and model performance was evaluated using the area under the curve (AUC) and Hosmer-Lemeshow (HL) goodness-of-fit test.

Results: RIHT developed in 4 % of patients with a median follow-up of 77.7 months. LKB and multivariable NTCP models exhibited significant agreement between the predicted and observed results (HL values > 0.05). The multivariable NTCP model outperformed the LKB model in predicting RIHT (AUC 0.62 vs. 0.54). In the multivariable model, systemic therapy, age, and percentage of thyroid volume receiving ≥ 10 Gy (V10) were significant prognostic factors for RIHT. The cumulative incidence of RIHT was significantly higher in patients who exceeded the cut-off values for all three risk predictors (systemic therapy, age ≥ 40 years, and thyroid V10 ≥ 26 %,  < 0.005).

Conclusions: Systemic therapy, age, and V10 of the thyroid were identified as strong risk factors for the development of RIHT. Our NTCP models provide valuable insights to clinicians for predicting and preventing hypothyroidism by identifying high-risk patients.