February 2017

Interventional News: RAI Helps Defeat Thyroid Cancer
By Richard Weiss, MD
Radiology Today
Vol. 18 No. 2 P. 6

This year, an estimated 64,300 adults (14,950 men and 49,350 women) in the United States will be diagnosed with thyroid cancer. It is now the most rapidly increasing cancer diagnosis in the United States and the fifth most common cancer in women. An estimated 1,980 people (910 men and 1,070 women) will die from thyroid cancer this year.1

While the increasing rates of thyroid cancer are troubling, the five-year survival rates indicate that treatment can be effective, especially the treatment of localized disease. The five-year survival rate for people with localized thyroid cancer is 98%. The 10-year and 15-year survival rates are 97% and 95%, respectively. If the cancer has spread to a distant part of the body, the five-year survival rate is 54%.1

The opportunity for long-term survival with thyroid cancer highlights the critical role that risk profiling, effective treatment, and ongoing monitoring play in patient management. In most cases, patients diagnosed with thyroid cancer are treated with surgical removal of the thyroid gland (thyroidectomy). Following removal of the gland and based on their established risk profile, appropriately selected patients are then treated with a procedure known as remnant ablation involving administration of radioiodine (RAI) to identify and kill any remaining cancer cells. (RAI is also often used in adjuvant therapy to identify and destroy unproven residual thyroid cancer and in therapy to treat persistent disease in high-risk patients.)2 According to guidelines set in 2015 by the American Thyroid Association, remnant ablation with RAI can be considered for low-risk patients and is generally favored for low- to intermediate-risk patients and recommended for patients at high risk of recurrence.2

In recent years, the range of options related to both administration of RAI and the imaging technologies used in the remnant ablation procedure have presented important new considerations to radiologists and oncologists to support effective management of thyroid cancer patients. The thyroid gland absorbs nearly all of the iodine circulating systemically in the body. As a result, when RAI is administered in patients, it has the targeted ability to concentrate in and kill thyroid cells, including any residual thyroid cancer cells. For remnant ablation with RAI to be effective, patients must have sufficient levels of thyroid-stimulating hormone (TSH or thyrotropin) in the blood. This hormone stimulates any remaining thyroid tissue to take up the RAI.

If the thyroid gland has been removed, one widely used method to raise TSH levels is to stop a patient's treatment with thyroid hormone replacement therapy for several weeks. This causes levels of TSH to rise but also increases the risk of a condition known as hypothyroidism (low thyroid hormone levels). While hypothyroidism will generally abate once thyroid hormone replacement therapy is resumed, it can cause a range of challenging symptoms including severe fatigue, depression, weight gain, constipation, muscle aches, and reduced concentration.3

Patients often report that symptoms of hypothyroidism can affect their ability to manage many day-to-day responsibilities. In just one example, a recent study of cognitive and motor impairment in patients with hypothyroidism concluded that complex activities requiring rapid responses, such as operating motor vehicles, should be avoided during severe iatrogenic hypothyroidism.4 In recent years, management of the remnant ablation process using RAI has increasingly focused on strategies to help reduce the risk of hypothyroidism.

Managing the RAI Ablation Process
In an empiric treatment model, following thyroidectomy treatment with thyroid hormone replacement therapy is either not initiated or is stopped to allow TSH levels to increase to approximately 25 to 30 mU/L. Patients are then treated with RAI (I-131) at doses ranging from 30 to 100 mCi. Between three and seven days following administration of recombinant human TSH (rhTSH), a whole body scan (WBS) is performed to identify any areas where the iodine was picked up.

In patients who continue treatment with thyroid hormone who are not hypothyroid, rhTSH is administered on days one and two to provide the necessary TSH stimulation. On day three the dose of I-131 (30 to 100 mCi) is given and WBS is performed between three and seven days later. Research has shown that rates of remnant ablation are comparable for patients treated with hormone withdrawal and for patients who continue treatment with thyroid hormone replacement therapy in conjunction with administration of rhTSH.5

In an alternative treatment model, a diagnostic preablation scan is performed in patients who are made hypothyroid or in patients who continue treatment with thyroid replacement hormone in conjunction with rhTSH. Patients are then given a tracer dose 4 mCi of I-131 and WBS is performed. In a study of 320 patients with differentiated thyroid cancer, use of preablation WBS with SPECT/CT technology resulted in changes in assessments of risk of recurrence in 15% of patients,6 and in diagnosis of stage of disease in 4% of younger patients and 25% of older patients.7

Recent studies have also demonstrated that use of RAI ablation is similarly effective with or without administration of treatment with rhTSH to reduce the risk of hypothyroidism.5 Among patients receiving RAI post total thyroidectomy, low-risk patients who show uptake of RAI outside of the thyroid bed, as well as all intermediate- and high-risk patients, should receive follow-up diagnostic testing including TSH stimulated WBS at six to 18 months.2

In addition to reducing a risk of hypothyroidism, use of rhTSH has also been shown to have an impact on RAI kinetics. RAI has a longer half-time in remnant tissue after rhTSH compared with thyroid hormone withdrawal, while the differences in uptake and residence time are not statistically significant.6 In patients treated with RAI with rhTSH for TSH stimulation, mean residence times of RAI in tissue and blood were significantly lower compared with patients utilizing thyroid hormone withdrawal as the method for TSH stimulation. This suggests use of rhTSH may lead to less of an undesired effect of RAI on the remainder of the body.8

The safety profile in patients receiving rhTSH either for diagnostic purposes or as adjunctive treatment for RAI ablation in patients who have undergone a thyroidectomy does not differ. In the combined clinical trials, reactions reported in patients greater than or equal to 1% include nausea, headache, fatigue, vomiting, dizziness, and asthenia.

Options in management of RAI have been further supported by the introduction of advanced imaging modalities able to provide more precise information related to uptake of RAI. SPECT/CT combines the information from a nuclear medicine SPECT with imaging from CT to support enhanced observation and staging of neoplastic disease. SPECT/CT RAI imaging can provide better anatomic localization of RAI uptake and distinguish between likely tumors and nonspecific uptake. Results from SPECT/CT can be used to confirm designations and modifications in patient risk assessments and correlating treatment protocols.6 In addition, updated collimators are available that can enhance imaging and address challenges associated with use of older cameras that produce lower-quality scans.

The prospects for long-term survival in thyroid cancer reinforce the need for clinicians and radiologists to continually assess the available interventional strategies and technologies that can help patients remain cancer-free while maintaining both overall health and quality of life. The application of different approaches in the administration of RAI coupled with access to advanced imaging technologies and procedures represent important considerations in development of treatment protocols able to support optimal outcomes for patients in the years ahead.

— Richard Weiss, MD, is the former global medical director, endocrinology-rare diseases of Sanofi-Genzyme.

1. American Cancer Society. Cancer facts & figures 2016. http://www.cancer.org/acs/groups/content/@research/documents/document/acspc-047079.pdf. Published 2016.

2. Haugen BR, Alexander EK, Bible KC, et al. 2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: the American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. 2016;26(1):1-133.

3. Schlumberger M, Catargi B, Borget I, et al. Strategies of radioiodine ablation in patients with low-risk thyroid cancer. N Engl J Med. 2012;366(18):1663-1673.

4. Smith CD, Grondin R, LeMaster W, Martin B, Gold BT, Ain KB. Reversible cognitive, motor, and driving impairments in severe hypothyroidism. Thyroid. 2015;25(1):28-36.

5. Pacini F, Ladenson PW, Schlumberger M, et al. Radioiodine ablation of thyroid remnants after preparation with recombinant human thyrotropin in differentiated thyroid carcinoma: results of an international, randomized, controlled study. J Clin Endocrinol Metab. 2006;91(3):926-932.

6. Avram AM, Esfandiari NH, Wong KK. Preablation 131-I scans with SPECT/CT contribute to thyroid cancer risk stratification and 131-I therapy planning. J Clin Endocrinol Metab. 2015;100(5):1895-1902.

7. Avram AM, Fig LM, Frey KA, Gross MD, Wong KK. Preablation 131-I scans with SPECT/CT in postoperative thyroid cancer patients: what is the impact on staging? J Clin Endocrinol Metab. 2013;98(3):1163-1171.

8. Hänscheid H, Lassmann M, Luster M, et al. Iodine biokinetics and dosimetry in radioiodine therapy of thyroid cancer: procedures and results of a prospective international controlled study of ablation after rhTSH or hormone withdrawal. J Nucl Med. 2006;47(4):648-654.