HOLLYWOOD, FLA. — The National Comprehensive Cancer Network has updated its thyroid carcinoma guidelines to add consideration of small molecule kinase inhibitors in metastatic disease treatment, refine diagnosis and treatment strategies based on fine-needle aspiration, and provide new information on thyroid-stimulating hormone suppression.
The panel of 26 physicians noted increasing off-label use of small molecule kinase inhibitors in patients with thyroid carcinoma. They said these agents can be considered to treat papillary, follicular, Hürthle cell, or medullary carcinoma, if a clinical trial is unavailable or inappropriate.
Although it's a drug class recommendation, “we specifically mention sorafenib and sunitinib as options,” Dr. Steven I. Sherman said at the annual conference of the National Comprehensive Cancer Network (NCCN). Best supportive care also remains a consideration for these patients with clinically progressive or symptomatic disease.
Neither kinase inhibitor is indicated for thyroid cancer. The Food and Drug Administration has approved sorafenib (Nexavar) in advanced renal cell carcinoma and hepatocellular carcinoma, and sunitinib (Sutent) in gastrointestinal stromal tumors and metastatic renal cell carcinoma. Both are under investigation in other tumors.
The NCCN revised procedures for evaluating thyroid nodules, especially follicular or Hürthle cell neoplasms and follicular lesions of undetermined significance that cannot be diagnosed by fine-needle aspiration (FNA). For an undetermined lesion, if the thyroid-stimulating hormone level is high or normal, repeat FNA and consider surgery based on clinical findings concerning growth or suspicious findings on ultrasound. If the TSH is low, perform a thyroid scan, and repeat FNA based on the same factors if the scan is cold; if it is hot, evaluate and treat for thyrotoxicosis. A follicular lesion of undetermined significance still carries a 5%–10% risk of cancer, Dr. Sherman said.
Diagnostic categories based on FNA findings have been updated. One category, for example, is patients who have or are suspected of having papillary, medullary, or anaplastic thyroid carcinoma. These patients have a 99% risk of cancer, and should go directly to primary treatment, said Dr. Sherman, department chair and professor of endocrine neoplasia and hormonal disorders at the University of Texas M.D. Anderson Cancer Center, Houston.
If the FNA indicates thyroid lymphoma, refer to NCCN Non-Hodgkin's Lymphoma Guidelines. If the FNA comes back as an insufficient biopsy or as nondiagnostic, treatment is dictated by whether it is cystic or solid. “An insufficient biopsy still carries a 1%–7% risk of cancer,” Dr. Sherman said.
For a benign thyroid nodule, the risk of cancer is 1% or less, Dr. Sherman said, and observation is recommended. However, if there is nodule growth, repeat the FNA or consider surgery.
Patient age over 45 years is no longer a factor that should raise clinical suspicion with a solitary thyroid nodule greater than 1 cm in diameter in the setting of an unknown TSH level, according to the new guidelines.
For patients with a positive FNA finding, the panel provides a less stringent recommendation for a chest radiograph: “Consider chest x-ray” instead of “chest x-ray, if not recently done.” There is greater consensus now behind the panel's recommendation to perform a lateral neck ultrasound in this group of patients.
The NCCN also added recommendations for the use of levothyroxine for TSH suppression in papillary, follicular, and Hürthle cell carcinomas. The use of levothyroxine is considered optimal to maintain low TSH levels and minimize risk of stimulating the growth of cells derived from thyroid follicular epithelium, but there are insufficient data to recommend serum TSH targets. Instead, the guidelines say, “in general, patients with known residual carcinoma or at high risk for recurrence should have TSH levels maintained below 0.1 mU/L, whereas disease-free patients at low risk for recurrence should have TSH levels maintained either slightly below or slightly above the lower limit of the reference range.” Patients who remain disease free for several years can probably have TSH levels maintained within the reference range.
The guidelines advise balancing risks and benefits of suppressive levothyroxine therapy for each patient. There is potential for cardiac tachyarrhythmias, bone demineralization, and thyrotoxicosis caused by TSH-suppressive doses. Also, patients on long-term suppression need an adequate intake of calcium (1,200 mg/day) and vitamin D (800 U/day).
Dr. Sherman is a consultant for and receives grant and research support from several pharmaceutical companies and the National Cancer Institute, and is on the speakers bureau for Genzyme.
Radioiodine Recommendations Refined
The National Comprehensive Cancer Network changed its recommendations for management of patients with thyroid carcinoma post thyroidectomy, especially concerning the use of radioiodine therapy.
Radioactive iodine (RAI) therapy is now an option for patients with no gross residual disease in the neck after surgery. “Postoperative RAI therapy is to destroy any remaining normal thyroid tissue as a source of thyroglobulin production, to improve accuracy of follow-up testing,” Dr. Sherman said.