RAI Treatment in DTC Survivors Associated With Increased Risk of Other Cancers

Radioactive iodine (RAI) treatment for patients with childhood and young-adulthood differentiated thyroid cancer (DTC) was associated with increased risks of several solid tumors, supporting the need for long-term surveillance of these patients.

Experts have previously determined RAI to be associated with increased risk of leukemia. However, the risks of second solid malignancies associated with this treatment remain unclear. As a result, a study aimed to understand the risks of second malignancies associated with RAI treatment for both children and young adult patients with DTC, who are more susceptible than older adults to the late effects of radiation.

Between 1975-2017, patients with primary DTC diagnosed before the age of 45 were identified using 9 surveillance, epidemiology, and end results (SEER) registries, covering 9% of the U.S. population. Relative risks (RR) for solid and hematologic malignancies associated with RAI were assessed 2 or 5 years after DTC diagnosis. DTCs were classified according to their size and lymph node involvement.

A total of 36,311 pediatric and young adult survivors with diagnosed nonmetastatic DTC were evaluated. Females made up 81% of the patients within the study and 45% were treated with RAI. Males depicted a higher rate in RAI use (50%) than females (44%), and the rate was highest among patients younger than 15 years of age (55%), and lowest in Black patients (40%).

Findings revealed that a total of 27,050 patients were 5+ year survivors, and 1,524 second solid malignancies were observed over the median follow-up of 15.6 years. Risks were increased for uterine cancer (RR = 1.55; 95% CI 1.03-2.32) as well as non-significantly for cancers including salivary gland (RR = 2.15; 95% Cl 0.91-5.08), stomach (RR = 1.61; 95% CI 0.70-3.69), lung (RR = 1.42; 95% CI 0.97-2.08), and female breast (RR = 1.18; 95% CI 0.99-1.40).

Additionally, risks of total solid and female breast cancer were reported as being the highest among 20-year and older DTC survivors (RRsolid = 1.47; 95% CI 1.24-1.74; RRbreast = 1.46; 95% CI 1.10-1.95).

Among 32,171 2+ year survivors, RAI was associated with increased risk of hematologic malignancies (RR = 1.51; 95% CI 1.08-2.01), including leukemia (RR = 1.92; 95% CL 1.04-3.56). A total of 146 of these patients were diagnosed with hematologic malignancies over a median follow-up of 13 years. It was also estimated that 6% of solid and 14% of hematologic malignancies in pediatric and young adult DTC survivors may be attributable to RAI.

The findings for both lung and uterine cancer were positive and somewhat stronger in the sensitivity analysis restricted to DTC diagnosed before age 40 years. Additionally, these data were consistent with previous studies.

The results showed an increased risk of hematologic malignancies following RAI treatment. There also was no association observed for lymphoid malignancies, which are not clearly radiation associated.

Cumulative incidence curves and RRs which were stratified by follow-up ended up staying consistent in showing different exposure latency periods for hematologic and solid malignancies, with shorter-term elevated risks for hematologic malignancies and longer-term elevated risks (increasing over time) for solid malignancies.

Overall, RAI therapy for DTC increases the leukemia risk starting approximately 2-3 years after exposure in pediatric and young adult patients with DTC. Further, RAI increases the risk of several types of solid cancer. More research and discussion on the evaluation of RAI therapy in the management in DTC of this patient population is needed to fully understand the benefits and make sure they outweigh the risks.

Reference

Pasqual E, Schonfeld S, Morton LM et al. Association between radioactive iodine treatment for pediatric and young adulthood differentiated thyroid cancer and risk of second primary malignancies. J Clin Oncol. 1;40(13):1439-1449. doi: 10.1200/JCO.21.01841.