Second Primary Malignancy Risk Following Radioactive Iodine Therapy for Thyroid Cancer: A Population-based Matched Cohort Study in Taiwan

OBJECTIVE: To investigate the association between radioactive iodine (RAI) treatment and the subsequent risk of second primary malignancies (SPMs) in thyroid cancer patients. DESIGN: Population-based propensity score-matched retrospective cohort study. METHODS: Data were obtained from the National Health Insurance Research Database, Cancer Registry, and Death Registry in Taiwan between 2001 and 2021. SPM was defined as any primary malignancy diagnosed more than one year following RAI treatment. Subdistribution hazard ratios (SHRs) with 95% confidence intervals (CIs) were estimated using a competing-risks survival analysis, adjusted for age, sex, and the Charlson comorbidity index (CCI). RESULTS: A total of 60,479 patients with thyroid cancer were identified. Following propensity score matching for sex, age, and CCI, the study cohort comprised 16,967 patients who received RAI and 16,967 patients who did not. RAI treatment was significantly associated with increased risk of salivary gland cancer (adjusted SHR, 2.87; 95% CI, 1.14-7.23; P, 0.026) and leukemia (adjusted SHR, 2.76; 95% CI, 1.23-6.20; P, 0.014). In addition, a 30-mCi increase in RAI dose was significantly associated with a higher risk of salivary gland cancer (adjusted SHR, 1.03; 95% CI, 1.01-1.06; P, 0.017) and leukemia (adjusted SHR, 1.04; 95% CI, 1.02-1.07; P < 0.001). CONCLUSIONS: Thyroid cancer patients treated with RAI have a significantly increased risk of developing salivary gland cancer and leukemia.