THYROID DYSFUNCTION IN HEAD AND NECK SQUAMOUS CELL CARCINOMA PATIENTS AFTER EXTERNAL RADIOTHERAPY

Abstract

Introduction/Justification: Head and neck squamous cell carcinoma (HNSCC) is the seventh leading cause of cancer in the world, and substantial morbidity and mortality have been attributed to the tumor effects. Radiotherapy (RT) alone or with chemotherapy (CHEMO) and/or surgery is a commonly used treatment but, despite its beneficial effects on tumor control, it can cause early and late adverse effects. RT can cause thyroid dysfunction (TD) in patients with HNSCC, but not all patients treated similarly develop TD. Objectives: The study aimed to identify TD among HNSCC patients submitted to external RT, and to identify risk factors for TD in these patients. Materials and Methods: This is a retrospective study focusing on early and long-term thyroid function in 285 HNSCC patients treated with RT alone or alone or combined with CHEMO and/or surgery. The patients were seen at diagnosis and follow up at the Clinical Oncology Service of the University Hospital between July 2001 and March 2016. The analysis of the thyroid function data of each patient included in study was done serially after the end of treatment, using free thyroxine (FT4) and thyroid-stimulating hormone (TSH) levels. The study was approved by the Institutional Human Research Ethics Committee (number: 2312237). Results: One-hundred fifty-six (54.7%) patients presented TD during follow-up, 153 (53.7%) in long-term. Subclinical hypothyroidism (SCH, 43.5%) was most common, of which 68.5% persisted SCH, 21% overt hypothyroidism, 0.8% central hypothyroidism, and 9.7% returned to euthyroidism at the study end. Mean time after RT for first TD detection was 7.2 months; 3.85 for subclinical thyrotoxicosis; 17.77 for SCH, 42.0 for long-term follow-up TD. Type 2 diabetes mellitus, tumor infiltration of lymph nodes, and no tumor resection were TD risk factors. About: One-hundred fifty-six (54.7%) patients presented TD during follow-up, 153 (53.7%) in long-term. Subclinical hypothyroidism (SCH, 43.5%) was most common, of which 68.5% persisted SCH, 21% overt hypothyroidism, 0.8% central hypothyroidism, and 9.7% returned to euthyroidism at the study end. Mean time after RT for first TD detection was 7.2 months; 3.85 for subclinical thyrotoxicosis; 17.77 for SCH, 42.0 for long-term follow-up TD. Type 2 diabetes mellitus, tumor infiltration of lymph nodes, and no tumor resection were TD risk factors. About SCH progression risk, a direct association with TSH was observed, all patients with TSH ≥ 7.5mIU/mL had primary hypothyroidism/SCH, whereas 19.5% with TSH < 7.5mIU/mL persisted euthyroid in long-term follow-up. Oral cavity tumors were associated with euthyroidism/SCH; pharynx/larynx with overt hypothyroidism. Conclusion: The data indicate the need for frequent monitoring of thyroid function in HNSCC patients treated with RT, particularly in those with type 2 diabetes mellitus, lymph nodes infiltrated by the tumor, and not submitted to surgical tumor resection. Acknowledgements: This study was supported by grants from the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES).

Keywords

• Head and neck squamous cell carcinoma
• Radiotherapy
• Thyroid dysfunction