Development of second primary cancer in radioiodine treated patients with differentiated thyroid carcinoma

Introduction: Development of second primary cancers (SPC) is a matter of concern in patients with differentiated thyroid carcinoma (DTC) especially after treatment with I-131. As many factors may interfere with the development of a second malignancy in DTC patients, the actual risk of SPC in treated patients with different doses of I-131 is under question. A retrospective cohort study was conducted to estimate the standardized rate of SPC and the associated factors after treatment with I-131 in patients with DTC. Methods: 973 DTC patients with history of radioiodine treatment were included in this study to calculate the age-standardized rate (ASR) of SPC using a direct method. In order to allow a minimum latency period for a radiation-induced cancer to occur after radioiodine therapy, the cases with a follow-up duration less than 3 years following initial I-131 treatment were not included in analysis. ASR of SPC and its 95% confidence interval (CI) during a median of 6 (from 3 to 26) years follow-up in the studied patients was compared with the data of general population. The ratio of ASR in the studied population to the ASR of cancers in the general population was defined as standardized rate ratio (SRR). A logistic multivariable regression analysis was applied to evaluate the effect of other potential covariates interfering with the risk of SPC after DTC treatment. Results: Eleven patients in 7370 patients-years at risk involved with SPC. The SRR of non-thyroid malignancies in the studied patients relative to the general population was 0.81 (95% CI: 0.57-1.04). In a multivariate model, the cumulative dose of I-131, age, follow-up duration, histology of DTC, presence/absence of metastasis and external radiotherapy were considered as potential covariate factors that may change the risk of SPC. In this model, the odds of SPC was significantly increased only when the cumulative dose of I-131 exceeded 40GBq (Odds ratio: 113; 95% CI: 8.6-1495.6; p<0.0001). Conclusion: The overall incidence of SPC following a minimum interval of 3 years from the first I-131 treatment may not be significantly increased on the whole population of patients with DTC; however, the chance of SPC may be increased in especial cases received a cumulative dose of I-131 exceeding 40GBq during repeated courses of treatments.