The Impact of Thyroid Gland Volume on the Risk of Developing Post-RT Hypothyroidism in Breast Cancer Patients Requiring Comprehensive Nodal Irradiation

Abstract

<h3>Purpose/Objective(s)</h3> Comprehensive nodal irradiation involving supraclavicular (SCV) nodes for breast cancer can unavoidably irradiate the thyroid gland to a significant dose. Based on a previously published normal tissue complication probability (NTCP) model [1], we evaluated the probability of developing hypothyroidism (HT) 5 years post proton radiation therapy for these patients. Based on the original model and our data, we developed an empirical correlation to predict the probability of developing HT based on the patient's thyroid volume before generating a treatment plan. <h3>Materials/Methods</h3> Fifty breast cancer patients (45 left- and 5 right-sided) received comprehensive intensity-modulated proton therapy between March 2020 and August 2021. The prescribed dose was 50.4 Gy to the chest wall or breast, SCV, axillary and internal mammary node target volumes. Two en-face beams, single-field-optimization and planning tool algorithm with robustness evaluation were used for planning to ensure that the target volumes received at least 95% of the prescription dose. The published NTCP model was used to predict the risk of developing HT 5 years after treatment. The key factors for the model are the mean thyroid dose (Dmean) and the total gland volume for small thyroids, and the thyroid gland receiving less than 20 Gy (CV20 Gy) for large thyroids. We established an empirical correlation between baseline thyroid volumes and the risk of developing HT, based on the received thyroid dose without sacrificing SCV coverage and robustness. <h3>Results</h3> Average values for total thyroid volumes, Dmean, and CV20 Gy were 10.3 cc (1.6, 64.0), 21.2 Gy (5.8, 34.9) and 5.7 cc (0.7, 37.4), respectively. The NTCP model for large thyroid glands predicts that the HT risk decreases exponentially as CV20 Gy increases; for small thyroids, the HT risk increases exponentially with decreasing thyroid volume, as well as with increasing Dmean. Our empirical correlation, based on the actual dose to the thyroid without compromising SCV coverage, showed that gland volume is a strong predictor for HT risk for small thyroids. Thyroid volume of 12.5 cc was derived from this correlation. For patients with larger than 12.5 cc thyroids, the 5-year HT risk is lower than 15%. For patients with thyroids < 12.5 cc, the 5-year HT risk is higher than 15%, and more significantly, it increased faster than the exponential decrease in thyroid volume. <h3>Conclusion</h3> Our empirical correlation indicates that patients with small thyroid glands (<12.5 cc) are substantially more likely to develop late post-RT HT. The risk of HT rapidly escalates >15% as gland volumes decrease < 12.5 cc. For such patients, more diligent dosimetric techniques to minimize gland dose, and proactive post-treatment surveillance for HT should be considered. [1] "NTCP model for hypothyroidism after supraclavicular-directed radiation therapy for breast cancer", HuaKang Huang, <i>et al</i>., Radiotherapy and oncology, 154 (2021) 87-92