Surgery May Prevent Rare Thyroid Cancer in At-Risk ChildrenKey Words
Thyroid cancer, childhood cancer, thyroidectomy, genetic screening. (Definitions of many terms related to cancer can be found in the Cancer.gov Dictionary.)
Summary
Forty-four of 50 children who carried a genetic mutation that causes a rare type of thyroid cancer, but who had no symptoms of the disease, remained disease-free five or more years after preventive surgery to remove the thyroid gland. However, longer follow-up is necessary to confirm that the complex procedure should be routinely done on all at-risk children.
Source
New England Journal of Medicine, Sept. 15, 2005 (see the journal abstract).
Background
A rare type of childhood cancer called medullary thyroid cancer can only be cured if surgery to remove the
thyroid gland (thyroidectomy) is performed before the disease develops or spreads beyond the thyroid. The operation is complex and patients must then take synthetic thyroid hormone for the rest of their lives.
In the early 1990s, researchers discovered that children who inherit one of several mutations in a gene known as RET are almost certain to develop medullary thyroid carcinoma. Such children can now be identified by a genetic screening test. The clinical trial described here was designed to find out whether this group of healthy but at-risk children could avoid medullary thyroid carcinoma by undergoing a preventive thyroidectomy.
The Study
Researchers started a genetic screening program in 1993 and eventually identified 85 patients who had inherited one of the RET mutations that causes medullary thyroid cancer. Eighty-three of these patients had surgery to remove the thyroid gland and were then followed for at least five years.
To determine whether or not patients developed cancer despite the surgery, researchers relied on a blood test which measures the level of a substance called calcitonin, which is produced by medullary thyroid cancer cells. Elevated levels of calcitonin are considered one sign of disease.
Researchers also gathered information about other physical characteristics of the patients to see if any of these factors would predict which patients were most likely to benefit from the preventive surgery. Examples of such factors included which specific RET mutation the patients had, the particular location of the mutation on the gene, age at the time of surgery, and whether cells in the removed thyroid gland or in the nearby lymph nodes showed signs of cancer.
In this report, researchers provide results from 50 patients who were between three and 19 years old at the time of surgery. The study’s lead author is Michael A. Skinner, M.D., of Duke University School of Medicine in Durham, North Carolina.
Results
Forty-four of the 50 patients - including all of those who were under the age of eight when they had their surgery - were cancer free when examined at least five years later, as determined by the calcitonin blood test.
Researchers were unable to reliably determine why six of the patients did develop cancer despite the surgery, though age may have been a factor since all of them were older than eight. Lymph node status may also have been influential: of the three patients who had cancerous lymph nodes at the time of surgery, two went on to develop cancer within five years. Otherwise, none of the other factors studied by the researchers appeared to predict an outcome.
Limitations
Although these findings are encouraging, say the study authors, more patients need to be followed for a longer time after surgery to confirm that early surgical removal of the thyroid gland does prevent or cure hereditary medullary thyroid cancer.
The study report does not mention the possible complications of thyroidectomy in young children, says Barry Anderson, M.D., Ph.D., a pediatric cancer specialist with the National Cancer Institute. Such surgery-related complications may include nerve and vocal cord damage, permanent impairment of the parathyroid gland that regulates calcium levels in the body, bleeding into the neck tissues and, rarely, death. Due to their smaller neck structure, children are more likely than adults to experience these complications after surgery, note Francis D. Moore, M.D., and Robert G. Dluhy, M.D., of Brigham and Women’s Hospital in Boston, Mass., in an accompanying editorial.
In addition, the study is not a randomized controlled trial, generally considered to be the “gold standard” for establishing whether a treatment is safe and effective. In a randomized trial, patients would be assigned at random to have surgery or not. However, because children identified as carrying a RET mutation are almost certain to get medullary thyroid cancer without surgery, it would be inappropriate to conduct a trial in which some patients were not offered surgery, says Anderson.
Comments
“This study demonstrates that preventive surgery at a young age averts the development of medullary thyroid cancer in patients with a RET mutation, at least for the five years that the patients were followed,” says Anderson. He cautions that the surgery should be done only at pediatric specialist centers where all staff are highly trained and experienced in performing such surgery on very young patients.
Editorialists Moore and Dluhy echo this advice, adding that the surgery should be performed at the earliest age at which it is safe to do so. They also recommend that each center employ a genetic counselor whose role includes providing information and emotional support to patients and their families.
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