Is radioactive iodine- 131 treatment related to the occurrence of non-synchronous second primary malignancy in patients with differentiated thyroid cancer?

Abstract

Objective: Much controversy relates to the risk of non-synchronous second primary malignancies (NSSPM) after radioactive iodine treatment (RAI-131) in differentiated thyroid cancer (DTC) patients. This study evaluated the relationship between RAI-131 and NSSPM in DTC survivors with long-term follow-up. Materials and methods: Retrospective analysis of 413 DTC cases was performed; 252 received RAI-131 and 161 were treated with thyroidectomy alone. Exclusion criteria were: prior or synchronous non-thyroidal malignancies (within the first year), familial syndromes associated to multiple neoplasms, ionizing radiation exposure or second tumors with unknown histopathology. Results: During a mean follow-up of 11.0 ± 7.5 years, 17 (4.1%) patients developed solid NSSPM. Patients with NSSPM were older than those without (p = 0.02). RAI-131 and I-131 cumulative activity were similar in patients with and without NSSPM (p = 0.18 and p = 0.78, respectively). Incidence of NSSPM was 5.2% in patients with RAI-131 treatment and 2.5% in those without RAI-131 (p = 0.18). Using multivariate analysis, RAI-131 was not significantly associated with NSSPM occurrence (p = 0.35); age was the only independent predictor (p = 0.04). Under log rank statistical analysis, after 10 years of follow-up, it was observed a tendency of lower NSSPM-free survival among patients that received RAI-131 treatment (0.96 vs. 0.87; p = 0.06), what was not affected by age at DTC diagnosis. Conclusion: In our cohort of DTC survivors, with a long-term follow-up period, RAI-131 treatment and I-131 cumulative dose were not significantly associated with NSSPM occurrence. A tendency of premature NSSPM occurrence among patients treated with RAI-131 was observed, suggesting an anticipating oncogenic effect by interaction with other risk factors. Arch Endocrinol Metab. 2016;60(1):9-15

Nonthyroidal second primary malignancies in differentiated thyroid cancer patients: Is the incidence increased comparing to the general population and could it be a radioiodine therapy consequence?

“…Our data are overall consistent with other studies described in the literature although among them there are differences in the inclusion and exclusion criteria used, definition of NTSPC, data collection method and median follow‐up period. In the paper by de Souza et al 11 the prevalence of NTSPC after an 11‐year median follow‐up period was lower than ours (4.1% in all DTC patients, 5.2% in 131‐I‐treated patients, and 2.5% in untreated patients) despite also including nonmelanoma skin cancer (squamous and basal cell cancer) in the group of NTSPCs. One possible explanation for the lower prevalence could be the shorter follow‐up period.…”

“…According to the data from Silva‐Vieira et al 9 collected from the South Portuguese regional cancer registry database, during a median follow‐up of 8.8 years, the prevalence of NTSPC in a Portuguese DTC population was 6%, in particular 8.2% in the 131‐I‐treated group and 4.8% in the untreated group. Additionally, in our study, the prevalence was lower, but the follow‐up period was even shorter than that of de Souza et al 11 Moreover, the data were collected from a regional cancer registry with no possibility of verifying all of the data collected by other nonreferral thyroid cancer centers. In the Korean paper by Khang et al, 8 after a 7‐year follow‐up period, the prevalence was 2.5% in the DTC population, 2.7% in the treated group and 2.2% in the untreated group, but there was no indication regarding the NTSPC histotype included and the follow‐up was even shorter.…”

“…The long‐term survival of DTC patients leads to the question of whether 131‐I treatment increases the lifetime risk of developing a nonthyroidal second primary cancer (NTSPC), especially in younger patients at diagnosis and in those who have been repeatedly treated. To date, the data conflict with some studies showing a higher risk of NTSPC in DTC patients compared to the general population and related to 131‐I therapy, 6‐9 and other studies suggesting that the higher incidence of NTSPCs could be explained by common genetic or environmental risk factors 10‐12 …”

Radioiodine for thyroid cancer: sometimes, less is best

“…An interesting observation of the study was that, probably, a tendency of premature NSSPM occurrence among patients treated with RAI exists. The author also concluded that patients with more advanced age at DTC diagnosis were under greater risk of NSSPM development (10).…”

“…(10), also presented a very controversial and interesting subject that challenges physicians treating DTC patients. The authors evaluate a large number of patients (n = 413) with histopathological diagnosis of thyroid cancer treated between January 1 st of 1979 and December 31 of 2009.…”