Advancing Education, Research, and Quality of Care for the Head and Neck oncology patient.
Introduction: Radioactive iodine (RAI) is commonly given after thyroidectomy to treat high-risk differentiated thyroid cancer (DTC). However, RAI has been linked to an increased risk of certain second primary malignancies (SPMs), especially in younger patients. This association may shift across age groups due to decreasing radiation sensitivity and remaining life span, but there is limited research on age-specific risk. Therefore, this study aims to assess whether RAI is associated with an increased risk of solid SPMs in adults aged 45 to 65.
Methods: 19,695 adults between the ages of 45 and 65 diagnosed with non-metastatic DTC were identified from eight SEER Registries (1975-2021). Patients were stratified into two groups according to whether they received RAI. Surveillance for solid SPMs began five years after DTC diagnosis to account for the latency period of radiation carcinogenesis. Surveillance ended at time of SPM diagnosis, death, last follow-up, or December 31st, 2021, whichever occurred first. Using the SEER database, the observed and expected number of SPMs by cancer site were used to calculate relative risks (RRs), 95% confidence intervals (CI), and the excess number of SPMs attributable to RAI using Poisson regression models. All analyses were done in SEER*Stat and SAS (Statistical Analysis System, Version 9.4, Cary, NC).
Results: The overall risk of solid SPMs was not elevated for RAI-treated patients (RR=0.94, 95% CI, 0.76 to 1.16). Risks were significantly increased for prostate (RR=1.61, 95% CI, 1.10 to 2.37) and salivary gland cancers (RR=10.22, 95% CI, 1.27 to 82.24), and significantly decreased for brain cancers (RR=0.21, 95% CI, 0.06 to 0.74). There was no increased risk of cancers of the digestive system, breast, corpus uteri, endocrine system, lung and bronchus, skin, ovary, soft tissue, and vulva. We estimated that 2.14 excess prostate cancers and 0.80 excess salivary gland cancers per 10,000 person-years were attributable to RAI. Of note, 9 cases of “other endocrine” cancers occurred in the RAI-treated group versus 0 in the non-RAI group, whereas 16 cases of vulvar cancers occurred in the non-RAI group versus 0 in the RAI group.
Conclusion: Increased risks of salivary gland and prostate cancers were found following RAI in adults aged 45 to 65. Multiple other studies have found an increased risk of salivary gland cancer after RAI in pediatric and young adult patients; this may be due to Na+/I- symporter expression driving RAI accumulation in the salivary gland. Our finding of increased prostate cancer risk may be attributable to confounding factors such as more vigilant screening and higher access to care in the RAI-treated group. There was no increased risk of 22 other solid cancers. Given this data, the benefits of RAI may far outweigh the risks for most patients aged 45 to 65. Physicians may need to closely monitor DTC survivors aged 45 to 65 who received RAI for salivary gland and prostate cancers, even in the absence of other risk factors. Future research should focus on the relationship between RAI dose and the risk of specific SPMs and how it varies across age groups.