Variation of normal tissue complication probability (NTCP) estimates of radiation-induced hypothyroidism in relation to changes in delineation of the thyroid gland.

BACKGROUND: To examine the variations of risk-estimates of radiation-induced hypothyroidism (HT) from our previously developed normal tissue complication probability (NTCP) model in patients with head and neck squamous cell carcinoma (HNSCC) in relation to variability of delineation of the thyroid gland. PATIENTS AND METHODS: In a previous study for development of an NTCP model for HT, the thyroid gland was delineated in 246 treatment plans of patients with HNSCC. Fifty of these plans were randomly chosen for re-delineation for a study of the intra- and inter-observer variability of thyroid volume, Dmean and estimated risk of HT. Bland-Altman plots were used for assessment of the systematic (mean) and random [standard deviation (SD)] variability of the three parameters, and a method for displaying the spatial variation in delineation differences was developed. RESULTS: Intra-observer variability resulted in a mean difference in thyroid volume and Dmean of 0.4 cm(3) (SD ± 1.6) and -0.5 Gy (SD ± 1.0), respectively, and 0.3 cm(3) (SD ± 1.8) and 0.0 Gy (SD ± 1.3) for inter-observer variability. The corresponding mean differences of NTCP values for radiation-induced HT due to intra- and inter-observer variations were insignificantly small, -0.4% (SD ± 6.0) and -0.7% (SD ± 4.8), respectively, but as the SDs show, for some patients the difference in estimated NTCP was large. CONCLUSION: For the entire study population, the variation in predicted risk of radiation-induced HT in head and neck cancer was small and our NTCP model was robust against observer variations in delineation of the thyroid gland. However, for the individual patient, there may be large differences in estimated risk which calls for precise delineation of the thyroid gland to obtain correct dose and NTCP estimates for optimized treatment planning in the individual patient.

External validation of a normal tissue complication probability model for radiation-induced hypothyroidism in an independent cohort.

BACKGROUND: A normal tissue complication probability (NTCP) model for radiation-induced hypothyroidism (RIHT) was previously derived in patients with squamous cell carcinoma of the head and neck (HNSCC) discerning thyroid volume (Vthyroid), mean thyroid dose (Dmean), and latency as predictive factors. The purpose of this study was to test the performance of this model in an independent cohort of patients receiving primary radiotherapy (RT) for HNSCC. MATERIAL AND METHODS: A validation cohort of 198 patients with HNSCC was included after plasma thyrotropin (TSH) assessment. RIHT was defined as TSH > 4.0 mU/l from blood samples obtained during follow-up. A new mixture NTCP model was developed from the validation cohort after multivariable analysis. Due to only one follow-up TSH assessment in the validation cohort, the time factor derived from the original cohort was fixed in a mixture model and applied for the NTCP validation. Association between model predictions of the initial model and observed clinical outcome in the validation cohort was investigated by applying the previous model (Vthyroid, Dmean and time) on the new cohort and comparing it to the clinical outcome. RESULTS: Both Dmean and Vthyroid were confirmed as significant risk factors for RIHT in the validation cohort, odds ratio (OR) 1.19 (1.1-1.37) and OR 0.75 (0.57-0.9), respectively. A small difference in overall probability of RIHT was observed between the cohorts, further analysis indicated this to be related to less frequent blood tests in the validation cohort relative to the original cohort. However, Pearson's correlation coefficients between model and clinical outcome were high: r = 0.97 estimated by the original model versus the original cohort, and r = 0.97 estimated by the original model versus the new cohort. CONCLUSION: Dmean and Vthyroid were significant predictors of RIHT in both cohorts. The original NTCP model demonstrated external validity owing to high Pearson's correlation coefficients between estimated and observed incidence rates of RIHT in the original as well as in the validation cohort. This model may facilitate clinically relevant estimations of RIHT after RT to the neck.