Meta-analysis of secondary hematologic malignancy risks following radioactive iodine therapy for differentiated thyroid cancer.

[PURPOSE] Radioactive iodine (RAI) therapy remains a widely accepted and effective intervention for differentiated thyroid cancer (DTC). Nonetheless, concerns persist regarding the potential emergence of second primary malignancies following RAI exposure. To assess the association between RAI administration and the risk of secondary hematologic malignancies in DTC patients, a meta-analysis was conducted.

[METHODS] A systematic literature search was performed via PubMed and Web of Science, conforming to PRISMA guidelines.

[RESULTS] Seventeen studies, including a total of 586 260 DTC patients, were included in the final analysis. The aggregated risk ratio (RR) for secondary hematologic malignancies among those treated with RAI was 1.25 (95% CI: 1.13-1.38, P< 0.0001), compared with non-RAI recipients. Heterogeneity across studies was minimal ( I2  = 8%). Further subgroup analyses were conducted based on malignancy subtype and RAI dosage. The RR estimates by subtype were as follows: non-Hodgkin's lymphoma, 0.91 (95% CI: 0.72-1.16, P = 0.45); Hodgkin's lymphoma, 1.17 (95% CI: 0.62-2.21, P = 0.63); myeloma, 0.90 (95% CI: 0.59-1.37, P = 0.62); and leukemia, 1.52 (95% CI: 1.05-2.21, P = 0.03). For patients receiving RAI doses below 3.7 GBq, the pooled RR was 0.39 (95% CI: 0.22-0.72, P = 0.002). Sensitivity and subgroup analyses reinforced the robustness and internal consistency of these findings. No publication bias was detected via Egger's regression or Begg's funnel plot ( P =  0.511).

[CONCLUSION] These results suggest a potential elevation in the risk of secondary hematologic malignancies - particularly leukemia - following RAI therapy in DTC patients. However, administration of RAI at doses below 3.7 GBq may not confer such risk. Additional large-scale, multicenter prospective investigations are warranted to validate these observations.