I-131 Best Practice Or In Need of Use Revision?
The U.S. yearly incidence of thyroid cancer diagnosis has increased from 3.6 per 100,000 in 1973 to 8.7 per 100,000 in 2002—a 2.4-fold increase in almost 30 years, according to David S. Cooper, MD, professor of medicine, Johns Hopkins University School of Medicine, Baltimore, and chair of the American Thyroid Association (ATA) Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid Cancer. He and colleagues published ATA revised management guidelines in November 2009 for patients with thyroid nodules and differentiated thyroid cancer. In 2011, an estimated 48,020 new cases of thyroid cancer were diagnosed (CA Cancer J Clin 2011;61[4]:212-236).
Differentiated thyroid cancer, which includes papillary and follicular cancer, comprises 90 percent of all thyroid cancers and the trend doesn’t seem to be abating any time soon, wrote Cooper et al. They attribute the increase in differentiated thyroid cancer largely to the 2.9 fold increase of papillary thyroid cancer between 1988 and 2002. “Moreover, 49 percent of the rising incidence consisted of cancers measuring 1 cm or smaller and 87 percent consisted of cancers measuring 2 cm or smaller,” they wrote. Much of the increase may be related to detection bias from ever-increasing amounts of imaging (CT scans, MRI, carotid Doppler) being done.
Thyroidectomy is the standard treatment for well-differentiated thyroid cancer. Radioactive iodine oftentimes is given to patients after total thyroidectomy to ensure full eradication of remnant thyroid tissue and to treat potential residual disease. There’s little controversy to the value of radioactive iodine for advanced-stage, well-differentiated thyroid cancer patients, wrote Megan R. Haymart, MD, divisions of metabolism, endocrinology and diabetes and hematology/oncology at University of Michigan Health System (UMHS), Ann Arbor, and colleagues (JAMA 2011;306(7):721-728).
“I-131 is one of the better treatments in all of medicine because it’s so targeted,” echoes Pieter L. Jager, PhD, MD, Isala Clinics, Zwolle, the Netherlands. He says Holland’s universal use of I-131 for remnant ablation allows the use of thyroglobulin as a tumor marker. “With thyroglobulin as a tumor marker, there should be none present [after sugery or remnant ablation] indicating no residual thyroid tissue or tumor,” Cooper adds. “Six to 12 months later, we can give the patient recombinant thyroid stimulating hormone and measure thyroglobulin to assess whether the patient is ‘free of disease.’ But, if you don’t give radioactive iodine, you can’t do the test since the stimulated thyroglobulin will rise due to remnant tissue, making the interpretation of the test impossible.”
“In contrast, for very low-risk disease, in which prognosis is typically excellent, treatment with radioactive iodine is of uncertain benefit,” wrote Haymart et al. “Opponents counter that mortality secondary to thyroid cancer is sufficiently low, negating the need for the unnecessary health risks, including secondary cancer following radioactive iodine.” Also, the costs associated with I-131 use can reach upwards of $4,724 per patient and $940,215 to the overall cost to the U.S. healthcare system (Arch Otolaryngol Head Neck Surg 2007;133[9]:870-873).
An incidence of second primary malignancy is also of concern. Van Nostrand says the pros and cons of I-131 use have to be considered in light of the objective. He describes three categories of objectives: remnant ablation; adjuvant treatment; and treating a disease has already spread to other sites such as lung, bone or liver.
With remnant ablation, I-131 seeks to rid the body of any normal thyroid tissue a surgeon may have left behind, which allows physicians track a patient’s thyroglobulin more effectively. “Since low-dose radiation is typically used for this, the radiation is warranted relative to the side effects in selected patients,” says Van Nostrand.
I-131 adjuvant treatment is administered to get rid of suspected, but unproven, residual malignant thyroid tissue as well as when there is suspicion that cancer has spread. “Adjuvant is usually a higher dose with the goal of a cure. ATA’s guidelines state if there is patient who has a known spread of thyroid cancer outside the thyroid involving a lymph node, the treatment has potential value to the patient,” Van Nostrand says. “Weighing the potential benefits and risks, the higher dose is frequently warranted.”
The objective of treating patients with thyroid cancer that has spread may involve much higher doses of radioactive iodine. “One has to weigh the benefits and the risks involving side effects that now include secondary primary malignancies. It becomes a tougher choice,” he says. “However, one might accept the risks with a patient who has a good uptake of iodine.”
Sisson et al wrote that the two major principles guide radiation safety: sound medical practice and adherence to regulations (Thyroid 2011;21[4]:335-346). They advised that I-131 therapy for thyroid disease can be performed within Nuclear Regulatory Commission regulations by evaluating the requirements for individual patients and giving advice on reducing radiation exposures through appropriate and patient specific precautions.
One potential tool is the use of radioiodine SPECT/CT, which has been reported to change clinical management and risk stratification of patients between 25-47 percent of patients (J Nucl Med 2012;53[5]:754-764).
Van Nostrand has found that at WHC that the use of I-131 hasn’t decreased per se, but has become “smarter.” Use is “down in low-risk patients with a tumor of 1 cm or less,” he says. “However, the referral of patients with metastatic disease has gone up, and as a result, so has the use of I-131.” Noting that WHC sees about six to eight patients a week with metastatic disease, Van Nostrand reports that the provider’s appropriate use of I-131 has become better.
Cooper also uses I-131 less frequently in low-risk patients and not at all in patients with tumors less than a centimeter in diameter. In Cooper et al’s revised management guidelines for patients with thyroid nodules and differentiated thyroid cancer, radioiodine is not recommended in patients with micropapillary cancer, even when it is multifocal. “I’m hoping that the ATA guidelines ultimately will result in fewer people getting radioactive iodine,” he says.
Differentiated thyroid cancer, which includes papillary and follicular cancer, comprises 90 percent of all thyroid cancers and the trend doesn’t seem to be abating any time soon, wrote Cooper et al. They attribute the increase in differentiated thyroid cancer largely to the 2.9 fold increase of papillary thyroid cancer between 1988 and 2002. “Moreover, 49 percent of the rising incidence consisted of cancers measuring 1 cm or smaller and 87 percent consisted of cancers measuring 2 cm or smaller,” they wrote. Much of the increase may be related to detection bias from ever-increasing amounts of imaging (CT scans, MRI, carotid Doppler) being done.
Thyroidectomy is the standard treatment for well-differentiated thyroid cancer. Radioactive iodine oftentimes is given to patients after total thyroidectomy to ensure full eradication of remnant thyroid tissue and to treat potential residual disease. There’s little controversy to the value of radioactive iodine for advanced-stage, well-differentiated thyroid cancer patients, wrote Megan R. Haymart, MD, divisions of metabolism, endocrinology and diabetes and hematology/oncology at University of Michigan Health System (UMHS), Ann Arbor, and colleagues (JAMA 2011;306(7):721-728).
“I-131 is one of the better treatments in all of medicine because it’s so targeted,” echoes Pieter L. Jager, PhD, MD, Isala Clinics, Zwolle, the Netherlands. He says Holland’s universal use of I-131 for remnant ablation allows the use of thyroglobulin as a tumor marker. “With thyroglobulin as a tumor marker, there should be none present [after sugery or remnant ablation] indicating no residual thyroid tissue or tumor,” Cooper adds. “Six to 12 months later, we can give the patient recombinant thyroid stimulating hormone and measure thyroglobulin to assess whether the patient is ‘free of disease.’ But, if you don’t give radioactive iodine, you can’t do the test since the stimulated thyroglobulin will rise due to remnant tissue, making the interpretation of the test impossible.”
“In contrast, for very low-risk disease, in which prognosis is typically excellent, treatment with radioactive iodine is of uncertain benefit,” wrote Haymart et al. “Opponents counter that mortality secondary to thyroid cancer is sufficiently low, negating the need for the unnecessary health risks, including secondary cancer following radioactive iodine.” Also, the costs associated with I-131 use can reach upwards of $4,724 per patient and $940,215 to the overall cost to the U.S. healthcare system (Arch Otolaryngol Head Neck Surg 2007;133[9]:870-873).
Risky business
Radioactive iodine also brings its share of risks and concerns. The acute short-term risks associated with I-131 use, Cooper says, include nausea and salivary gland pain and swelling. Long-term side effects, says Douglas Van Nostrand, MD, division of nuclear medicine, Washington Hospital Center (WHC), Washington, D.C., include the salivary glands swelling potentially leading to xerostomia (chronic dry mouth). “This can cause more frequent dental cavities and disease,” says Van Nostrand.An incidence of second primary malignancy is also of concern. Van Nostrand says the pros and cons of I-131 use have to be considered in light of the objective. He describes three categories of objectives: remnant ablation; adjuvant treatment; and treating a disease has already spread to other sites such as lung, bone or liver.
With remnant ablation, I-131 seeks to rid the body of any normal thyroid tissue a surgeon may have left behind, which allows physicians track a patient’s thyroglobulin more effectively. “Since low-dose radiation is typically used for this, the radiation is warranted relative to the side effects in selected patients,” says Van Nostrand.
I-131 adjuvant treatment is administered to get rid of suspected, but unproven, residual malignant thyroid tissue as well as when there is suspicion that cancer has spread. “Adjuvant is usually a higher dose with the goal of a cure. ATA’s guidelines state if there is patient who has a known spread of thyroid cancer outside the thyroid involving a lymph node, the treatment has potential value to the patient,” Van Nostrand says. “Weighing the potential benefits and risks, the higher dose is frequently warranted.”
The objective of treating patients with thyroid cancer that has spread may involve much higher doses of radioactive iodine. “One has to weigh the benefits and the risks involving side effects that now include secondary primary malignancies. It becomes a tougher choice,” he says. “However, one might accept the risks with a patient who has a good uptake of iodine.”
Sisson et al wrote that the two major principles guide radiation safety: sound medical practice and adherence to regulations (Thyroid 2011;21[4]:335-346). They advised that I-131 therapy for thyroid disease can be performed within Nuclear Regulatory Commission regulations by evaluating the requirements for individual patients and giving advice on reducing radiation exposures through appropriate and patient specific precautions.
More appropriate use
For adjuvant therapy following total thyroidectomy from 2004 to 2008, Haymart et al found a statistically significant difference in radioactive iodine use between the American Joint Committee on Cancer Stages I and IV, but not for Stage II or Stage III vs. Stage IV. “The adjusted odds ratio suggests that for every one additional case a hospital treats, the odds of radioactive iodine use increase by 0.6 percent after adjusting for patient and tumor characteristics and hospital type,” the authors wrote. “We would anticipate for a lower stage disease, your prognosis is going to be better and some of these patients may not need radioactive iodine but instead what we’re seeing is that Stage II, III and IV are receiving similar rates of treatment which suggests we need to tailor radioactive iodine use to disease severity and not treat all thyroid cancers the same.”One potential tool is the use of radioiodine SPECT/CT, which has been reported to change clinical management and risk stratification of patients between 25-47 percent of patients (J Nucl Med 2012;53[5]:754-764).
Van Nostrand has found that at WHC that the use of I-131 hasn’t decreased per se, but has become “smarter.” Use is “down in low-risk patients with a tumor of 1 cm or less,” he says. “However, the referral of patients with metastatic disease has gone up, and as a result, so has the use of I-131.” Noting that WHC sees about six to eight patients a week with metastatic disease, Van Nostrand reports that the provider’s appropriate use of I-131 has become better.
Cooper also uses I-131 less frequently in low-risk patients and not at all in patients with tumors less than a centimeter in diameter. In Cooper et al’s revised management guidelines for patients with thyroid nodules and differentiated thyroid cancer, radioiodine is not recommended in patients with micropapillary cancer, even when it is multifocal. “I’m hoping that the ATA guidelines ultimately will result in fewer people getting radioactive iodine,” he says.