Radiation-Induced Hypothyroidism in Patients With Breast Cancer After Hypofractionated Radiation Therapy: A Prospective Cohort Study

Abstract

Our objective was to assess the incidence and risk factors of radiation-induced hypothyroidism (RHT) after adjuvant hypofractionated radiation therapy (RT) in patients with breast cancer. Eligible patients with breast cancer who were treated with hypofractionated RT were prospectively evaluated. Thyroid function tests were performed before and at regular times after RT. RHT was defined as twice elevated serum thyroid-stimulating hormone (TSH) with decreased or normal free thyroxin after RT. The patient, tumor, and treatment factors were evaluated for possible associations with the risk of RHT. Five hundred patients were analyzed. All patients underwent chest wall/breast with or without regional nodal irradiation. Among them, 369 (73.8%) patients received supraclavicular nodal radiation (SCRT). Eighty-two (16.4%) patients had elevated TSH before RT. At a median follow-up of 21.9 months, 131 (26.2%) patients developed RHT, and 59 (11.8%) patients received thyroid hormone-replacement therapy. Patients with SCRT had a significantly increased 2-year cumulative incidence of RHT compared with patients without SCRT (31.5% and 11.4%, P<.001). The peak incidence of RHT occurred around 6 to 12 months after RT. Multivariate analysis revealed that elevated baseline TSH and increased thyroid mean dose (Dmean) were independent risk factors for developing RHT. After adjusted for baseline TSH, there was a nonlinear relationship between thyroid Dmean and the risk of RHT. Dmean >21 Gy was the threshold value for predicting RHT (hazard ratio, 2.2; P<.001). The incidence of RHT was high in patients with breast cancer. Thyroid function test should be started no later than 6 months after RT. We recommend that the Dmean of the thyroid should be kept lower than 21 Gy for hypofractionated RT.