Sodium Iodide I-131

To investigate the association between radioactive iodine (RAI) treatment and the subsequent risk of second primary malignancies (SPMs) in thyroid cancer patients.

Population-based propensity score-matched retrospective cohort study.

Data were obtained from the National Health Insurance Research Database, Cancer Registry, and Death Registry in Taiwan between 2001 and 2021. SPM was defined as any primary malignancy diagnosed more than one year following RAI treatment. Subdistribution hazard ratios (SHRs) with 95% confidence intervals (CIs) were estimated using a competing-risks survival analysis, adjusted for age, sex, and the Charlson comorbidity index (CCI).

A total of 60 479 patients with thyroid cancer were identified. Following propensity score matching for sex, age, and CCI, the study cohort comprised 16 967 patients who received RAI and 16 967 patients who did not. RAI treatment was significantly associated with increased risk of salivary gland cancer (adjusted SHR, 2.87; 95% CI, 1.14-7.23; P, .026) and leukemia (adjusted SHR, 2.76; 95% CI, 1.23-6.20; P, .014). In addition, a 30-mCi increase in RAI dose was significantly associated with a higher risk of salivary gland cancer (adjusted SHR, 1.03; 95% CI, 1.01-1.06; P, .017) and leukemia (adjusted SHR, 1.04; 95% CI, 1.02-1.07; P < .001).

Thyroid cancer patients treated with RAI have a significantly increased risk of developing salivary gland cancer and leukemia.

Differentiated thyroid cancer (DTC) is the most common endocrine malignancy among children, adolescents, and young adults (CAYA). While prognosis is generally favorable, rising incidence, longer survivorship, and radioactive iodine (RAI) treatment raise concern for late effects, particularly second primary malignancies (SPMs) and late mortality.

To evaluate SPM risk, all-cause mortality, and the impact of RAI in CAYA DTC survivors.

Retrospective cohort study (1982–2022) using Clalit Health Services records, including DTC patients diagnosed <40 years, who survived ≥2 years. Participants were matched to cancer-free controls (1:4) by birth year, sex, ethnicity, and socioeconomic status. Cox models estimated hazard ratios (HRs) with 95% confidence intervals (CIs).

Among 5267 DTC survivors ( n = 497 [∼9.5%] diagnosed before age 20 years) and 21,062 matched controls, SPM incidence was higher in survivors with 50% increased risk (500 vs. 360 per 100,000 person-years; HR 1.50, CI 1.34–1.67) and occurred after a shorter latency (13.8 vs. 15.1 years; p = 0.042). Survivors diagnosed before age 20 were significantly younger at data retrieval than those diagnosed at 20–40 years (median 33 vs. 47 years; p < 0.001) and had significantly lower SPM rates ( n = 28 [5.6%] vs. n = 398 [9.0%]; p = 0.012). Compared with RAI-untreated survivors, SPM risk increased after one RAI treatment (HR 1.91, CI 1.52–2.40) and further after ≥2 RAI treatments (HR 2.73, CI 2.13–3.50). Overall mortality rate was low ( n = 148, 2.8%) and similar to that of matched controls ( n = 517, 2.5%) but was significantly higher among survivors who developed SPMs and/or received RAI treatment ( p < 0.001).

Over four decades of follow-up, SPMs were identified as a significant long-term risk among CAYA DTC survivors, frequently manifesting many years after the initial diagnosis. Both SPM occurrence and higher cumulative RAI doses were associated with increased mortality. These findings support careful risk-adapted use of RAI and underscore the need for extended surveillance, particularly for those diagnosed in childhood or adolescence, as malignancies may arise many years after diagnosis.