Linear Association between Radioactive Iodine Dose and Second Primary Malignancy Risk in Thyroid Cancer.

BACKGROUND: We aimed to investigate whether the risk of second primary malignancy (SPM) in TC patients receiving RAI therapy increases in a cumulative dose-dependent manner compared to those without.

METHODS: Using the Korean National Health Insurance Service-National Health Information Database (NHIS-NHID, 2002-2019), we investigated hazard ratios (HRs) of SPM associated with RAI in TC. SPM was defined as a second primary malignancy diagnosed at least 1 year after TC diagnosis.

RESULTS: Of 217,777 TC patients (177,385 women and 40,392 men; mean age, 47.2 ± 11.6 years), 100,448 (46.1%) received RAI therapy. The median follow-up duration was 7.7 years (interquartile range [IQR]: 5.5-10.3) and the median cumulative RAI dose was 3.7 GBq (IQR 1.9-5.6). During 2004-2019, SPM incidence rates were 7.30 and 6.56 per 1,000 person-years in the RAI and non-RAI groups, respectively, with an unadjusted HR of 1.09 (95% CI, 1.05-1.13); this remained at 1.08 (95% CI, 1.04-1.13) after adjustment for multiple clinical confounding factors. Notably, SPM risk increased significantly from 3.7 GBq with full adjustments, and a strong linear association between cumulative RAI dose and SPM was observed in the restricted cubic spline analysis. Regarding cancer subtypes, myeloid leukemia and salivary gland, trachea, lung and bronchus, uterus, and prostate cancers had the most significantly elevated risks in patients who underwent RAI therapy.

CONCLUSIONS: This study identified that SPM risk increased linearly in a dose-dependent manner in TC patients with RAI therapy compared to those without.