RAI Confers Excessive Secondary Malignancy Risk in the Young

Pam Harrison

September 25, 2012

September 25, 2012 (Quebec City, Quebec) — The risk of developing a secondary primary malignancy is excessive in children and young adults with well-differentiated thyroid cancer (WDTC) treated with radioactive iodine (RAI), new research shows.

Jennifer Marti, MD, from the Beth Israel Medical Center in New York City, and colleagues found that children and young adults with WDTC who were treated with RAI had a 42% excess risk of developing a secondary primary malignancy, compared with children and young adults who did not receive RAI.

"If the benefit of using RAI is unclear, one should consider these risks," Dr. Marti told delegates here at the American Thyroid Association 82nd Annual Meeting.

More Advanced Disease

Dr. Marti noted that children and young adults with WDTC present with more advanced disease — nodal metastasis, distant metastases, and extrathyroidal extension — than adults.

Despite this, mortality from thyroid cancer in children and young adults is low (below 2%), even in patients who do not receive RAI.

The investigators noted that in a large European registry, adults had a 27% greater cancer risk after RAI, and wanted to determine whether there was also an increased risk in children and young adults.

Dr. Marti and colleagues identified 3637 WDTC patients younger than 25 years from the Surveillance, Epidemiology and End Results (SEER) registry. Of these, 1587 patients received RAI and 2050 did not (44% vs 56%).

"We compared the number of cancers observed [in this registry] to the number of cancers expected; this gave us the excess risk, which we expressed as a standardized incidence ratio [SIR]," Dr. Marti explained.

Weigh the Risks

Overall, 20-year survival was excellent in the RAI and no-RAI groups (98.5% vs 97.3%).

"When we looked at the use of RAI over time, we saw a dramatic increase in use, from 4% in 1973 to 62% in 2008. The risk of a secondary primary malignancy also increased with increasing use of RAI," Dr. Marti added.

The investigators found that the SIR for all cancer sites was 1.42 for the RAI group and 1.01 for the no-RAI group — or a 42% excess risk of developing a secondary primary malignancy after receiving RAI.

The most dramatic increase in risk was in salivary cancer, which was 34-fold higher in the RAI group than in the no-RAI group (hazard ratio, 34.12; P = .0007).

There was also an almost 4-fold increase in the risk for leukemia in the RAI group, but this did not reach statistical significance (P = .09).

"The absolute elevated risk is low, with only 1 excess secondary primary malignancy for every 227 patients treated with RAI over 10 years. These low risks should not dissuade one from treating a patient with RAI if the patient will benefit," Dr. Marti said.

"However, when the benefit is not clear, these data help illuminate the risks of administering RAI to young patients with WDTC," she added.

Certain Circumstances

Sylvia Asa, MD, PhD, from the University of Toronto, in Ontario, Canada, told Medscape Medical News that, as with any other treatment, RAI is still necessary in certain circumstances.

For example, if a tumor is widely metastatic, "you need to deal with any residual tumors because once it's out of the thyroid and has spread to sites where you might lose control of it, you have to treat it. In these circumstances, the benefit [of RAI] outweighs the risk," she said.

However, in low-risk cancers that are localized to the thyroid or that present as micrometastases in local lymph nodes, RAI might not be effective if put to a clinical test.

"I think what this study shows is that where there is no clear indication for RAI, it's probably better not to use it, and for low-risk cancers, that's where this really makes a difference."

Dr. Marti and Dr. Asa have disclosed no relevant financial relationships.

American Thyroid Association (ATA) 82nd Annual Meeting: Oral abstract 5. Presented September 20, 2012.