Abstract
ObjectiveTo analyze the impact of nutritional counseling on the development of hypothyroidism after (chemo)radiotherapy in head and neck cancer patients to propose a new normal tissue complication probability (NTCP) model.Materials and methodsAt baseline, at the end of (chemo)radiotherapy, and during follow-up, thyroid-stimulating hormone (TSH) with free thyroxin (fT3 and fT4), nutritional status, and nutrient intake were prospectively analyzed in 46 out of 220 screened patients. Patients received (chemo)radiotherapy within an intervention (individual nutritional counseling every 2 weeks during therapy) and a control group (no nutritional counseling).ResultsOverall median follow-up was 16.5 [IQR: 12; 22] months. Fourteen patients (30.4%) presented with hypothyroidism after 13.5 [8.8; 17] months. During (chemo)radiotherapy, nutritional status worsened in the entire cohort: body mass index (p < 0.001) and fat-free mass index (p < 0.001) decreased, calorie deficit (p = 0.02) increased, and the baseline protein intake dropped (p = 0.028). The baseline selenium intake (p = 0.002) increased until the end of therapy. Application of the NTCP models by Rønjom, Cella, and Boomsma et al. resulted in good performance of all three models, with an AUC ranging from 0.76 to 0.78. Our newly developed NTCP model was based on baseline TSH and baseline ferritin. Model performance was good, receiving an AUC of 0.76 (95% CI: 0.61–0.87), with a sensitivity of 57.1% and specificity of 96.9% calculated for a Youden index of 0.73 (p = 0.004; area = 0.5).ConclusionBaseline TSH and ferritin act as independent predictors for radiotherapy-associated hypothyroidism. The exclusion of such laboratory chemistry parameters in future NTCP models may result in poor model performance.
Highlights
Methods radiotherapy constitutes a curative therapeutic approach for squamous cell carcinoma of the head and neck (HNSCC), it is often associated with a significant dose to the thyroid gland
Radiotherapy-induced thyroid dysfunction can lead to primary manifest hypothyroidism or subclinical hypothyroidism, Hashimoto’s thyroiditis, or Graves’ disease
N/A not applicable, RT radiotherapy, TSH thyroid-stimulating hormone, 95% CI 95% confidence interval, BMI body mass index, FFMI fat-free mass index, VxGy thyroid volume receiving x Gy, CVxGy thyroid volume receiving ≤ x Gy aNone of the diabetic and none of the unilaterally irradiated patients presented with the endpoint hypothyroidism
Summary
Methods radiotherapy constitutes a curative therapeutic approach for squamous cell carcinoma of the head and neck (HNSCC), it is often associated with a significant dose to the thyroid gland. Primary hypothyroidism is considered the most common radiotherapy-induced thyroid disorder and affects 20–60% of patients receiving irradiation to the neck [1, 2]. It usually occurs within 5 years after therapy completion [1]. Prior thyroidectomy and the applied irradiation dose are risk factors for hypothyroidism [1, 3, 4]. Apart from the applied radiation dose, the occurrence of hypothyroidism correlates with a reduction in thyroid volume [2, 7, 8]
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