Radioactive Iodine Treatment of Thyroid Cancers Increases Risk of MDS

The incidence of well-differentiated thyroid cancers (WDTC) has been rising steadily in the United States over the past three decades, mainly due to improved detection of subclinical disease (tumors < 2 cm). At the same time, there’s growing concern about the risk of secondary cancers in thyroid cancer patients treated with radioactive iodine, a potential carcinogen.

Now Cleveland Clinic researchers have found that thyroid cancer patients who undergo surgery and adjuvant radioactive iodine therapy — a common treatment for WDTC tumors — with or without external beam radiotherapy (EBRT), have an increased risk of myelodysplastic syndromes (MDS). Results of their research, was presented at the 57th American Society of Hematology Annual Meeting & Exposition in December in Orlando, Fla.

“Thyroid cancer is the most common endocrine cancer in the United States, and we are treating an increasing number of these cancers using both surgery and radioactive iodine,” says Sudipto Mukherjee, MD, PhD, lead researcher and associate staff member in Cleveland Clinic’s Department of Hematology and Medical Oncology.

“Because we’re detecting many of these cancers when they are small (< 2cm) — and there is lack of data demonstrating better survival with radioactive iodine — we may be overtreating them. As a result, we could be exposing low-risk thyroid cancer patients to the risk of secondary cancers including hematologic malignancies years later,” Dr. Mukherjee says.

MDS risk appears to be increased within the first two years of treatment with radioactive iodine

In Cleveland Clinic’s investigation, summarized in the abstract Radioactive Iodine Treatment of Thyroid Cancer and Risk of Myelodysplastic Syndromes, researchers examined 18 Surveillance Epidemiology and End Results (SEER) registries to identify well-differentiated thyroid cancers treated with surgery, radioactive iodine and EBRT, and the later development of myelodysplastic syndromes as secondary cancers. In all, 132,157 WDTC cancer patients treated from 1973 to 2011 were identified. Of these patients, 53 percent were treated with surgery alone, while 45 percent underwent surgery plus adjuvant radioactive iodine therapy. Two percent underwent external beam radiotherapy and surgery with or without adjuvant radioactive iodine treatment. Patients were followed for a median of five to six years after thyroid cancer treatment.

A total of fifty-five patients developed MDS. Of these, 24 had undergone surgery alone, while 27 received surgery plus radioactive iodine. Four patients had EBRT. Compared to those treated with surgery alone, thyroid cancer patients who received radioactive iodine with or without EBRT had an increased risk of developing MDS within the first two years of treatment (RR=1.9 vs. RR=5.8), researchers found.

Beyond two years, however, the risk for MDS in those treated with radioactive iodine dropped to baseline rates comparable to the general population, Dr. Mukherjee says. Interestingly and of concern, a trend towards a rise in MDS incidence was observed starting at 12 years after treatment, among those who underwent radioactive iodine therapy, but this did not reach statistical significance.

Study results reinforce need for measured treatment response, long-term research

Dr. Mukherjee notes that the reason behind early increased rates of MDS in patients treated with radioactive iodine remains unclear and needs to be investigated.

“The results could be an ascertainment bias,” he says. “The increased risk could be real, or it could be that increased rates of MDS in patients receiving radioactive iodine therapy is an effect of these patients being seen more frequently by oncologists and hence being diagnosed earlier than those undergoing surgery alone.”

Still, the results indicate that there is a risk of MDS with radioactive iodine therapy and oncologists should exercise caution when treating low-risk WDTC tumors, especially when there is paucity of data suggesting any efficacy of adjuvant radioactive iodine in preventing recurrences or prolonging survival in these patients, Dr. Mukherjee suggests.

“For some patients with small WDTC cancers without high risk features particularly extension beyond thyroid gland or lymph node involvement, the American Thyroid Association guidelines does not support routine use of radioactive iodine for these low-risk tumors. We don’t want to overtreat these patients, and so, we should weigh the risks of treatment very carefully,” he says.

In conclusion, the abstract notes, “Considering the long latency of MDS seen in atomic bomb cohorts with risk persisting beyond 40 years, there is a growing clinical concern that MDS rates are likely to rise in WDTC patients due to a combination of factors including relative young age of WDTC patients at the time of diagnosis, a high proportion of long-term survivors and the recent trend in overdiagnosing and subsequently overtreating WDTCs.”