Thyroid Cancer in Childhood Cancer Survivors: Demographic, Clinical, Germline Genetic Characteristics, Treatment, and Outcome

Abstract

Objective: Childhood cancer survival rates have improved, but survivors face an increased risk of second malignant neoplasms (SMNs), particularly thyroid cancer. This study examines the demographic, clinical, genetic, and treatment characteristics of childhood cancer survivors who developed thyroid cancer as a second or third malignancy, emphasizing the importance of long-term surveillance. Methods: A retrospective review was conducted for childhood cancer survivors treated between 1990 and 2018 who later developed thyroid cancer as a second or third malignancy. Data on demographics, clinical characteristics, treatment, and outcomes were analyzed. Results: Among the 3204 childhood cancer survivors, 10 patients (6 female, 4 male) developed papillary thyroid carcinoma (PTC), a median of 9 years post-initial diagnosis. Radiation therapy, particularly to the head and neck, was commonly used. Genetic testing revealed mutations in the Cell Cycle CheckPoint Kinase 2 (CHEK2) and Adenomatous Polyposis Coli (APC) genes in four patients, possibly contributing to the increased risk. All were diagnosed through thyroid ultrasound and underwent total thyroidectomy, and three received radioactive iodine (RAI). No recurrences or deaths related to PTC occurred, with a median follow-up of 5.5 years after diagnosis. Conclusions: Radiation therapy, especially combined with chemotherapy, significantly increases the risk of thyroid cancer in childhood cancer survivors. Genetic predispositions also play a role. Lifelong thyroid cancer surveillance is essential, particularly for those who received radiation or chemotherapy. Further research is needed to refine surveillance strategies and better understand genetic factors that influence thyroid cancer risk. Early detection and ongoing monitoring are critical for improving long-term outcomes.