Association Between Thyroid Radiation Dose and Hypothyroidism in Breast Cancer Patients Undergoing Volumetric Modulated Arc Therapy for Regional Nodal Irradiation

Background/Aim: To investigate the association between the thyroid dysfunction and thyroid radiation dose in regional nodal irradiation (RNI) using volumetric modulated arc therapy (VMAT) for breast cancer. Patients and Methods: We reviewed medical data of 67 patients with breast cancer who underwent curative surgery followed by adjuvant radiotherapy, including RNI using VMAT, between 2018 and 2021. All patients had normal thyroid functional test results, including thyroid stimulating hormone (TSH), T3, and free-T4. We defined subclinical hypothyroidism as increased TSH with or without decreased levels of free-T4 and T3 after the completion of VMAT. We calculated dose-volume histogram parameters (DVHPs), including the mean dose and relative thyroid volume receiving at least 10, 20, 30, and 40 Gy. Results: The median follow-up time was 23.2 months. The 3-year locoregional failure-free survival, progression-free survival, and overall survival rates were 96.3%, 94.7%, and 96.2%, respectively. The mean thyroid dose was 21.4 Gy (range=11.5- 29.4 Gy). Subclinical hypothyroidism was noted in 14 patients (20.9%) and the median time to the event was 4.1 months. Among the DVHPs, the relative volume receiving ≥20 Gy (V20Gy) was associated with subclinical hypothyroidism. The 2- year rates of subclinical hypothyroidism were 24.8% and 59.1% in patients with V20Gy ≤46.3% and >46.3%, respectively. Conclusion: A significant proportion of patients with breast cancer developed subclinical hypothyroidism after undergoing VMAT for RNI. Our findings highlight the importance of considering the thyroid as an organ at risk for VMAT planning, and suggest that V20Gy could be a useful dose-volume constraint.