Overtreatment a Concern With RAI for Well-Differentiated Thyroid Cancer

Patients with well-differentiated thyroid cancer (WDTC) treated with radioactive iodine (RAI) appear to have an increased early risk of developing acute myeloid leukemia (AML) or chronic myeloid leukemia (CML), according to a new study published in the Journal of Clinical Oncology. The study turned up no increased earlier risk for any other hematologic malignancies.  The findings suggest that RAI use in patients with WDTC should be limited to patients with high-risk disease features.

“In today’s day and age of evidence-based medicine, any therapeutic approach offered to the patient should be done so with a careful risk-benefit analysis. As our findings show, at least for WDTC patients who have low risk tumors, RAI treatment is unnecessary and does put patients at a small but significant risk for AML and CML,” said study investigator Sudipto Mukherjee, MD, MPH, of the Department Hematology and Medical Oncology at the Cleveland Clinic, in Cleveland, Ohio.

THE STUDY

The authors write that papillary and follicular thyroid carcinomas are classified as WDTCs and today make up 90% of all thyroid cancer cases in the United States. They reviewed the risk and outcomes of second hematologic malignancies (SHMs) in 148,215 patients with WDTC identified from the Surveillance Epidemiology and End Results (SEER) registry. Among these patients, 53% underwent surgery alone and 47% underwent surgery followed by RAI.

After a median interval of 6.5 years, 783 patients developed leukemia (417 after surgery alone and 366 after surgery plus RAI). The team conducted a multivariable analysis and found that RAI treatment was significantly associated with early risk of developing AML (hazard ratio [HR], 1.79) or CML (HR, 3.44).

WHAT WAS LEARNED

The study showed that the increased risks of AML and CML after RAI treatment was demonstrated even in low-risk and intermediate-risk WDTC tumors. In addition, the study suggested that occurrence of AML but not CML was associated with shorter median overall survival (OS) compared with matched controls.  Patients who developed AML after RAI trended toward inferior survival compared with matched controls with de novo AML, according to the investigators.

“We did not observe any increase in risk of other hematologic malignancies, Hodgkin disease, non-Hodgkin lymphoma, acute lymphocytic leukemia, chronic lymphocytic leukemia, and multiple myeloma. The risk of AML and CML peaked early, in the second year following RAI exposure,” Dr Mukherjee told Oncology Nurse Advisor.

The researchers write that patients with WDTC treated with adjuvant RAI should be monitored for myeloid malignancies as part of cancer surveillance. Dr Mukherjee said in the last 3 decades incidence of WDTC in the United States has increased fourfold.  Most of this increase is attributed to improved detection of low-risk tumors. 

There have been no published data showing any benefit from RAI in patients with low-risk tumors. “Yet, there has been a staggering increase in the use of RAI in this patient population going from 6.1% in 1973 to 49.8% in 2006. Our findings show overtreating low-risk WDTC patients with RAI carries small but significant early risk of AML and CML,” said Dr Mukherjee.

IMPLICATIONS FOR NURSES

Dr Mukherjee said these new findings have significant clinical implications and discussing these latest findings with patients is paramount.  “While the risk is low, it is not trivial particularly for those developing AML as they have inferior survival. Oncology nurses should be aware of these findings as they are so commonly involved in patient education and counseling as part of the oncology team and can help increase awareness of these findings. This is a patient-safety issue,” said Dr Mukherjee.

The researchers write that appropriately monitoring blood counts to detect development of myeloid malignancies is important in the management of patients with WDTC treated with RAI. In 2009, the American Thyroid Association issued guidelines on RAI use and since then there has been a modest decrease in its use, according to the researchers. Dr Mukherjee said strict adherence to these guidelines cannot be stressed enough.

“There is a risk of overtreating low-risk thyroid cancers. There is an increase in the risk of AML and CML. The risk is highest in the second year after RAI exposure. While the risk of AML gradually declines after 2 years and reaches general population rates by 6 years, the risk for CML remains significantly elevated up to 10 years after RAI exposure,” said Dr Mukherjee.

Reference

Molenaar RJ, Sidana S, Radivoyevitch T, et al. Risk of hematologic malignancies after radioiodine treatment of well-differentiated thyroid cancer [published online December 18, 2017]. J Clin Oncol. doi: 10.1200/JCO.2017.75.0232