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Use of RAI for Thyroid Cancer Comes Under Scrutiny

 |  By cclark@healthleadersmedia.com  
   August 18, 2011

Doctors may be increasingly using radioactive iodine inappropriately to treat early stage, low-risk thyroid cancer after surgery, contrary to the latest guidelines and with some evidence it will do more harm than good, according to a report from the University of Michigan.

Conversely, the study indicates that some patients with more clinically significant, higher-risk disease are not getting treated with radioactive iodine according to guidelines.

"Our study findings indicate there's variation in care, and that's suggestive that there is some provider uncertainty in regard to which patients actually need radioactive iodine," Haymart said in a phone interview.


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"For certain groups, radioactive iodine treatments are clearly beneficial, but for other groups, the patients are going to do well no matter what you do in regard to treatment, so the risk of using radioactive iodine really needs to be considered," said Megan R. Haymart, MD, author of the study.

"The recent guidelines (issued in 2009 by the American Thyroid Association) say those with very low risk disease don't need it, but there's a huge middle ground – a gray zone – where they leave it to the provider's discretion. So it's very possible that some of those patients don't need it as well."

Haymart pointed to research from others that show "if you diagnose more low-risk disease, there's an inflated belief that the treatment is working when, in fact, the patient would have done fine either way. I'm sure that's playing a role."

Haymart, an endocrinologist who specializes in thyroid disease, is the lead author of a paper published Wednesday in the Journal of the American Medical Association. The project looked at 189,219 patients with well-differentiated thyroid cancer treated at 981 hospitals between 1990 and 2008.

The researchers highlighted the rapid rise in the use of radioactive iodine to treat thyroid cancer, which went from 40% in 1990 to 56% in 2008.  "After adjusting for patient, tumor, and hospital characteristics," they wrote, "29.1% of the variance was attributable to unexplained hospital characteristics."

The issue is controversial in large part because of the unexplained rise in diagnoses of thyroid cancer in recent years. Incidences are accelerating "at a faster rate than any other malignancy," but most are very small at the earliest stage, she said.

For example, in 2009, the National Cancer Institute estimated there would be 37,200 people diagnosed with thyroid cancer. In 2011, the American Cancer Society estimates, the number will be 48,020, with expected mortality this year at a relatively low 1,740.

While some speculate that environmental changes may be at the root of increased diagnoses, Haymart and others suspect that increased use of imaging is more likely the cause.

Instead of recognizing thyroid disease by palpation, cases are being captured through tests done for other reasons, such as during examinations after accidents or to rule out heart disease.

"Most think that the largest component of the reason is the increased use of imaging. We're imaging more and more, and we're picking up more potentially indolent disease."

Thyroid cancer is largely a young person's disease, and the average age of those diagnosed is currently 49. However, 16% of the new patients diagnosed are between the ages of 20 and 34 while another 20% are between 35 and 44.

Use of radioactive iodine, while mostly safe, can involve side effects and complications, such as adverse impacts on quality of life, damage to local tissue such as salivary glands, and additional adverse effects. In rare cases, radiation can result in secondary cancers such as leukemia.

Haymart says a further review of the study's results will reveal regional trends in use of radioactive iodine in low-risk patients, so the reasons for more aggressive care may become a bit clearer.

"There was a wide between-hospital variation in radioactive iodine use, and much of the variance was attributable to unexplained hospital characteristics," the researchers wrote. An upcoming report will further analyze use of radioactive iodine in various groups of patients by hospital.

In an accompanying editorial, however, Edward Livingston, MD, and Robert McNutt, MD, of the division of gastrointestinal and endocrine surgery at the University of Texas Southwestern Medical Center in Dallas questioned Haymart's findings.

"The authors conclude that the substantial between-hospital variation in RAI use suggests clinical uncertainty and perhaps inappropriate use of radioactive iodine in thyroid cancer management," they wrote.

"However, there is incomplete knowledge about how and why care was delivered in hospitals showing variation."  For example, the database that the researchers used did not explain patient preferences or physician reasoning for why it may not have been given to a high-risk patient or why it was given to a low-risk one.

"Some surgeons leave a rim of thyroid tissue adjacent to nerves to minimize the risk of nerve injury, and rely on RAI to ablate the residual thyroid tissue," Livingston and McNutt argued. " Such surgeons have made a conscious risk-benefit decision balancing nerve injury with the risks of RAI."

They added, "these scenarios fall into the realm of individual clinician judgment and decision making. Consequently, variation is to be expected."

Haymart, however, said that the guidelines' indication for RAI is related to disease, "not whether there is thyroid tissue around the nerve."

In conclusion, Haymart and colleagues wrote that while radioactive iodine after surgery "is appropriate therapy for certain well-differentiated thyroid cancers, the benefit of radioactive iodine may not always exceed the risks.

"There is a clear role for adjuvant therapy with radioactive iodine in iodine-avid, advanced stage, well-differentiated thyroid cancer; however, there is unclear benefit to radioactive iodine use in low risk disease because patients with low-risk disease have an excellent prognosis, regardless of intervention."

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