Risk of second primary malignancies following radioactive iodine therapy in thyroid cancer: A meta-analysis of 1,189,992 patients

<ns3:p>While the prognosis of thyroid cancer (TC) was generally excellent, there was a long-term concern regarding the risk of subsequent second primary malignancies (SPM) following radioactive iodine (RAI). This study aimed to comprehensively estimate the pooled risk of SPM occurrence following RAI therapy. The study searched the literature across three databases (PubMed, Scopus, and ScienceDirect), and was followed by citation searching. Original observational studies assessing the risk of SPM following RAI in TC were included. The Newcastle Ottawa scale was used for methodological assessment. STATA 17.0 was used for statistical analysis. A total of 18 studies encompassing 1,189,992 patients were included (638,275 in the RAI group and 551,717 in the non-RAI group). Pooled meta-analysis demonstrated no statistically significant increase in the risk of SPMs in the RAI-treated group, with a pooled RR of 1.07 (95% CI: 0.96 –1.21; p = 0.23). This result was deemed robust based on leave-one-out analysis. Subgroup analysis across publication year, follow-up duration (>10 years vs ≤10 years), population size, and SPM site (including breast, genitourinary, gastrointestinal-hepatobiliary, respiratory, skin, hematology, central nervous system, head and neck) consistently showed comparable results. There was no evidence of a significantly increased risk of SPM among TC survivors treated with RAI.</ns3:p>