Incidence of Second Primary Malignancies During a Long-term Surveillance of Patients With Differentiated Thyroid Carcinoma in Relation to Radioiodine Treatment

Purpose: Controversies remain over the actual risk of developing a second primary malignancy (SPM) as a consequence of I-131 treatment in patients with differentiated thyroid carcinoma (DTC). The objective of this study was to evaluate the adjusted rate and risk estimate of SPM in radioiodine-treated patients after controlling for confounding factors. Materials and Methods: A retrospective cohort study was conducted on 973 cases randomly selected from a population of 9550 radioiodine-treated DTC patients. The cases with prior or coincident nonthyroid malignancies and those with SPM during the first 3 years of the initial I-131 treatment were not included. Age-standardized rate of SPM and its 95% confidence interval (CI) during a median of 6 (3-26) years follow-up in DTC patients was compared with that of the general population. A logistic multivariable analysis was also conducted to identify the potential covariate factors that might influence the risk of SPM. Results: Eleven patients from 7370 person-years at risk developed an SPM. The standardized rate ratio of nonthyroid malignancy was 0.81 (95% CI, 0.57-1.04) for the studied patients relative to the general population. The cumulative dose of I-131 more than 40 GBq (1.08 Ci) was the sole factor associated with increased odds of SPM, after adjusting for age, follow-up duration, histology of DTC, presence of metastasis, and history of external radiotherapy (odds ratio, 113; 95% CI, 8.6 -1495.6; P < 0.0001). Conclusions: The overall rate of SPMs was not significantly increased after a minimum interval of 3 years from the first I-131 treatment; however, the chance of this event may be radically increased in patients who had received a cumulative activity of I-131 exceeding 40 GBq (1.08 Ci).