Development of multivariate NTCP models for radiation-induced hypothyroidism: a comparative analysis

Background: Hypothyroidism is a frequent late side effect of radiation therapy of the cervical region. Purpose of this work is to develop multivariate normal tissue complication probability (NTCP) models for radiation-induced hypothyroidism (RHT) and to compare them with already existing NTCP models for RHT. Methods: Fifty-three patients treated with sequential chemo-radiotherapy for Hodgkin's lymphoma (HL) were retrospectively reviewed for RHT events. Clinical information along with thyroid gland dose distribution parameters were collected and their correlation to RHT was analyzed by Spearman's rank correlation coefficient (Rs). Multivariate logistic regression method using resampling methods (bootstrapping) was applied to select model order and parameters for NTCP modeling. Model performance was evaluated through the area under the receiver operating characteristic curve (AUC). Models were tested against external published data on RHT and compared with other published NTCP models. Results: If we express the thyroid volume exceeding X Gy as a percentage (V-x(%)), a two-variable NTCP model including V-30(%) and gender resulted to be the optimal predictive model for RHT (Rs = 0.615, p < 0.001. AUC = 0.87). Conversely, if absolute thyroid volume exceeding X Gy (V-x(cc)) was analyzed, an NTCP model based on 3 variables including V-30(cc), thyroid gland volume and gender was selected as the most predictive model (Rs = 0.630, p < 0.001. AUC = 0.85). The three-variable model performs better when tested on an external cohort characterized by large inter-individuals variation in thyroid volumes (AUC = 0.914, 95% CI 0.760-0.984). A comparable performance was found between our model and that proposed in the literature based on thyroid gland mean dose and volume (p = 0.264). Conclusions: The absolute volume of thyroid gland exceeding 30 Gy in combination with thyroid gland volume and gender provide an NTCP model for RHT with improved prediction capability not only within our patient population but also in an external cohort.