Evaluation of Risk Factors for Developing Hypothyroidism Following Radiation Therapy for Head and Neck Cancers

Abstract

<h3>Purpose/Objective(s)</h3> Hypothyroidism is a frequent late complication of Head and Neck radiotherapy. We sought to determine the incidence and risk factors for developing hypothyroidism after intensity modulated radiation therapy (IMRT) in patients with locally advanced head-and-neck cancer. We explored the hypothesis that baseline clinical characteristics and treatment factors would correlate with the development of hypothyroid. <h3>Materials/Methods</h3> We conducted an IRB approved retrospective review of patients with locally advanced head-and-neck cancer treated with radiotherapy at our institution. We determined the incidence as well as time to development of hypothyroidism defined as the initiation of hormone replacement or TSH value greater than 2-fold the normal assay limit. We then evaluated baseline clinical features including age, gender, tumor stage, tumor site in addition to clinical treatment factors including surgery, chemotherapy, and radiation dose for correlation with the development of hypothyroidism. <h3>Results</h3> We initially identified 207 subjects who completed radiation therapy between January 2015 and December 2017. We excluded patients who had hypothyroidism diagnosed before treatment, thyroid cancer, thyroidectomy or incomplete records yielding 147 evaluable patients with median follow-up time of 1.8 years. 77% of patients were male with mean age of 61 years (range 18-89). 58 of 147 evaluable patients (40.14%) developed hypothyroidism after a median of 12.7 months after radiation (range 2.6 to 44.4 months). Age, gender, stage, tumor site, and surgery did not show statistically significant correlation with the development with hypothyroidism. Mean Thyroid radiation dose correlated with the development of hypothyroidism (<i>P</i> < 0.01) on logistic regression modeling. 47.6 % of patients with mean thyroid dose greater than 40 Gy developed hypothyroidism compared to 18.7% of those receiving less than 40 Gy (<i>P</i> < 0.01, Chi-square test). Administration of chemotherapy was associated with hypothyroidism development after radiation (<i>P</i> < 0.05, Chi-square test). <h3>Conclusion</h3> Our institutional experience demonstrates hypothyroidism remains a frequent late complication with modern IMRT techniques. Mean thyroid dose correlates with the development of hypothyroidism. Intriguingly, administration of chemotherapy also correlates with the development of hypothyroidism. Ongoing aims include further characterizing the interaction of radiation therapy dose with chemotherapy in the development of hypothyroidism.