Second Primary Malignancy After Radioiodine Therapy in Thyroid Cancer Patient: A Nationwide Study

Objective: This study aimed to investigate the risk of second primary malignancy after radioiodine (RAI) therapy in patients with thyroid cancer, using the National Health Insurance Service (NHIS) database. Methods: We extracted data from the NHIS database of South Korea, which covers the entire population of the nation. Risk of second primary malignancy in the thyroid cancer patients who received RAI therapy were compared with the thyroid cancer patients who received surgery only. Results: Between January 1, 2004, and December 31, 2018, we identified 363,155 patients who underwent thyroid surgery due to thyroid cancer for analysis. The surgery only cohort was 215,481, and the RAI cohort was 147,674 patients. A total of 19,385 patients developed second primary malignancy (solid cancer, 18,285; hematologic cancer, 1,100). There was no significant increase in the risk of second primary malignancy in patients who received a total cumulative dose of 100 mCi or less (hazard ratio [HR], 1.013; 95% confidence interval [CI], 0.979–1.049). However, a statistically significant increase in the risk of second primary malignancy was observed in patients who received 101–200 mCi (HR, 1.214; 95% CI, 1.167–1.264), 201–300 mCi (HR, 1.422; 95% CI, 1.258–1.607), and > 300 mCi (HR, 1.693; 95% CI, 1.545–1.854). Conclusion: Total cumulative doses of 100 mCi or less of RAI can be safely administered without concerns about second primary malignancy. However, the risk of second primary malignancy increases in a dose-dependent manner, and the risk–benefit needs to be considered for doses over 100 mCi of RAI therapy.