Risk of Hematologic Malignancies After Radioiodine Treatment of Well-Differentiated Thyroid Cancer

Abstract

Purpose To investigate the risk and outcomes of second hematologic malignancies (SHMs) in a population-based cohort of patients with well-differentiated thyroid cancer (WDTC) treated or not with radioactive iodine (RAI). Methods Patients with WDTC were identified from SEER registries. Competing risk regression analysis was performed to calculate the risks of SHMs that occurred after WDTC treatment and outcomes after SHM development were assessed. Results Of 148,215 patients with WDTC, 53% received surgery alone and 47% received RAI. In total, 783 patients developed an SHM after a median interval of 6.5 years (interquartile range, 3.3 to 11.2 years) from WDTC diagnosis. In multivariable analysis, compared with those undergoing thyroidectomy alone, RAI treatment was associated with an increased early risk of developing acute myeloid leukemia (AML; hazard ratio, 1.79; 95% CI, 1.13 to 2.82; P = .01) and chronic myeloid leukemia (CML; hazard ratio, 3.44; 95% CI, 1.87 to 6.36; P < .001). This increased risk of AML and CML after RAI treatment was seen even in low-risk and intermediate-risk WDTC tumors. Occurrence of AML but not CML in patients with WDTC was associated with shorter median overall survival compared with matched controls (8.0 years v 31.0 years; P = .001). In addition, AML developing after RAI trended toward inferior survival compared with matched controls with de novo AML (median overall survival, 1.2 years v 2.9 years; P = .06). Conclusion Patients with WDTC treated with RAI had an increased early risk of developing AML and CML but no other hematologic malignancies. AML that arises after RAI treatment has a poor prognosis. RAI use in patients with WDTC should be limited to patients with high-risk disease features, and patients with WDTC treated with adjuvant RAI should be monitored for myeloid malignancies as part of cancer surveillance.

Therapy-related acute lymphoblastic leukemia is a distinct entity with adverse genetic features and clinical outcomes

“…5,6 Furthermore, a recent population-based cohort study identified a 3.4-fold higher risk for developing chronic myeloid leukemia and a 1.8-fold higher risk for developing AML after RAI treatment. 18 Therefore, Ph 1 ALL cases observed in our cohort might represent patients presenting with lymphoid blast crisis in the setting of a previously undiagnosed chronic myeloid leukemia. Altogether, the data suggest a possible link between RAI and Ph 1 hematologic cancers.…”

Radioactive Iodine Therapy for Differentiated Thyroid Cancer: Lessons from Confronting Controversial Literature on Risks for Secondary Malignancy

“…The paper by Molenaar et al and prior similar reports fueled growing pressure on NMSs to lower prescribed activity ranges (1,(6)(7)(8)(9). This trend has had a greater impact in countries where NMSs are not usually engaged in managing patients before and after RAIT.…”

“…On January 17, 2018, Dr. Mark Tulchinsky sent a petition to Dr. Stephen A. Cannistra, Editor-in-Chief of JCO, asking that the article by Molenaar et al (1) be retracted. This petition was supported and undersigned by 67 experts in nuclear medicine in 16 countries worldwide and included a rebuttal of the conclusions reached by the authors of that article.…”

“…The secondary malignancies evoke a particularly high level of concern in patients and health-care professionals because of potential grave consequences. A recent report by Molenaar et al aimed to clarify the risks of secondary hematologic malignancy (1). The investigators purported to show that RAIT was associated with an increased risk of acute and chronic myeloid leukemia.…”

“…Molenaar et al built the study cohort (148,215 patients with WDTC) from the Surveillance, Epidemiology, and End Results Program database (1). The authors state that ''a large population with relatively homogenous treatment exposure'' constituted the main strength of their study.…”