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 reviewed meeting data and published trials, and 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. 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 evaluation of thyroid nodules, especially follicular or Hürthle cell neoplasms and follicular lesions of undetermined significance that cannot be diagnosed by fine needle aspiration (FNA). For example, management of an undetermined lesion depends on whether thyroid stimulating hormone is high, normal, or low. If it 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 also changed in the guideline update. 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 in the division of internal medicine 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 nodule, the risk of cancer, at most, is 1%, he 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, available at www.nccn.org.
In addition, the NCCN added Principles of Thyroid Stimulating Hormone Suppression to the guidelines, providing specific recommendations for use of levothyroxine for TSH suppression in papillary, follicular, and Hürthle cell carcinomas.
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. The panel noted, however, that there are insufficient data to recommend appropriate serum TSH levels. Instead, “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.”
The NCCN also changed its recommendations for evaluation of patients with thyroid carcinoma post thyroidectomy, especially concerning use of radioiodine therapy. RAI is now an option for patients with no gross residual disease in the neck after surgery, “to destroy any remaining normal thyroid tissue as a source of thyroglobulin production,” said Dr. Sherman.
The guidelines now list RAI as an alternative at 1-12 weeks post thyroidectomy to a total body radioiodine scan. Clinical indications for RAI are based on pathology, postoperative thyroglobulin, and intraoperative findings.
The recommendations are specific by cancer stage. For example, radioiodine therapy for stage II disease “for the first time is associated with a survival advantage… with total or near-total thyroidectomy,” Dr. Sherman said. But “stage I is the problem. This is the largest group of patients, but clearly there is no evidence of a benefit of radioactive iodine therapy among stage I patients. This is a very important pullback in the recommendations.”
Dr. Sherman is a consultant for Bayer HealthCare, Celgene Corporation, Eisai Inc., Exelixis Inc., OXiGENE Inc., Plexxikon Inc., and Semafore Pharmaceuticals Inc. He receives grant and research support from Amgen, AstraZeneca, Eisai, Genzyme, and the National Cancer Institute, and is on the speakers bureau for Genzyme.
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