Hypothyroidism after Modern Photon or Proton Supraclavicular Nodal Irradiation for Breast Cancer

Abstract

<h3>Purpose/Objective(s)</h3> Hypothyroidism is associated with supraclavicular nodal irradiation (SNI) for breast cancer. Clinical and dosimetric characteristics affecting the risk of hypothyroidism have yet to be fully elucidated. This work sought to identify patient characteristics, technique factors, and thyroid dosimetric parameters that are associated with developing hypothyroidism in patients treated with SNI. <h3>Materials/Methods</h3> Medical records and treatment plans of 328 patients receiving postmastectomy radiotherapy including SNI at a single institution from 2015-2021 were reviewed; patients with a diagnosis of hypothyroidism or prior ipsilateral irradiation were excluded. Thyroid contours were standardized, and medial borders of SNI volume were reviewed. For patients not receiving 25 fractions, thyroid dosimetrics were normalized using biologic effective dose with an alpha/beta ratio of 3. Associations of hypothyroidism with patient/treatment characteristics (age, side, chemotherapy use, pre-SNI thyroid volume, fractionation, technique) and thyroid dosimetrics (V500, V1000, V2000, V2600, V3000, V4500 cGy) were evaluated using univariate Cox proportional hazard models. <h3>Results</h3> Forty-seven patients had a diagnosis of hypothyroidism prior to SNI, leaving 281 evaluable patients. Median patient age was 50 years, interquartile range (IQR) 42-60 years; 1% completed bilateral SNI, 53% left, 47% right; 67% received neoadjuvant chemotherapy, 33% adjuvant chemotherapy, 19% no chemotherapy; median thyroid volume was 9.7 cc, IQR 6.7-13.3 cc; 90% were prescribed 25 fractions, 10% 15 or 16 fractions; 67% underwent proton therapy, 30% 3D conformal, 3% volumetric modulated arc. At a median follow-up of 3.6 years, the cumulative incidence of hypothyroidism was 6.2% and 7.8% at 2 and 5 years, respectively. Ninety-seven (35%) of patients had completed thyroid function tests. On univariate analysis, only smaller thyroid volume was significantly associated with an increased risk of hypothyroidism (hazard ratio (HR) 0.23 per 10 cc, 95% confidence interval (CI) 0.07-0.83, p=0.02). Thyroid V500 cGy (median 57%, IQR 49-69%) approached but did not reach significance (HR 1.23 per 10%, 95% CI 0.99-1.63, p=0.06). Fourteen (5%) patients had died at last follow-up. <h3>Conclusion</h3> In a cohort of patients treated with modern radiotherapy techniques, rates of clinically apparent hypothyroidism after SCI were low, and most events occurred within the first two years. No thyroid dosimetric parameters were associated with the development of hypothyroidism, possibly due to a limited number of events.