Clinical and dosimetric factors for radiation-induced hypothyroidism following intensity-modulated radiotherapy in patients with head-and-neck cancer

Objective: To determine the clinical and dosimetric factors associated with radiation-induced hypothyroidism (HT) in head-and-neck cancer patients treated with intensity-modulated radiotherapy (IMRT). Methods: The clinical data of 28 head-and-neck cancer patients undergoing IMRT (with the prescribed radiation dose of neck ≥ 40 Gy) plus chemotherapy were retrospectively recruited. The serum levels of thyroid-stimulating hormone (TSH), free triiodo-thyronine (FT3), and free thyroxine (FT4) of each patient were recorded basally and at different times after the end of therapy. Primary HT was defined as increased TSH with or without decreased FT3 and/or FT4. Based on each patient's dose-volume histogram (DVH), the volume percentages of thyroid absorbing 5-50 Gy at interval of 5 Gy were estimated (marked as V_x, x = 5-50) together with the mean thyroid dose (MTD), maximum dose (D_max) and thyroid volume (TV). To evaluate the clinical and dosimetric factors associated with HT, univariate and multivariate logistic regression analysis were performed. Results: The median serum levels of TSH, FT3, and FT4 before treatment were 1.51 μU/ml, 5.38 pmol/L, and 18.57 pmol/L, respectively. During the follow-up time of of 15 months (3-57 months), 14 patients (50.0%) developed HT, and the median time for firstly detected HT was 8 months (2-23 months) after treatment. The median serum levels of TSH, FT3, and FT4 when HT was firstly detected were 7.48 μU/ml (4.67-60.11 μU/ml), 4.05 pmol/L (0.40-5.77 pmol/L), and 12.32 pmol/L (4.12-21.25 pmol/L) respectively. There was a significant increasing in TSH level in patients with HT during the follow-up (P < 0.05). The TV of the patients with HT was significantly lower than those without HT (Z = -2.154, P < 0.05). Univariate analysis showed that younger age and V₄₀ ≥ 80% were associated with a higher risk of HT (χ² = 11.340, 4.102; OR = 30.0, 9.17; P < 0.05). Multivariate analysis confirmed that age and V₄₀ were the independent predictors (OR = 34.7, 6.13; P < 0.05). Conclusions: HT after IMRT for head-and-neck cancer is accompanied by elevated TSH levels. Younger age, smaller thyroid volume, and V₄₀ ≥ 80% have been identified as risk factors for HT after IMRT. (authors)