Cancer Treatment Today

Veracyte’s Afirma Gene Expression Classifier test demonstrated in a multicenter, prospective validation study, published recently in the New England Journal of Medicine, that when it reclassified thyroid nodule FNA samples that were initially deemed indeterminate by cytopathology as benign which it did more than 50% of the time its accuracy was similar to a benign diagnosis using cytopathology.

The majority of FNAs of tyroid nodules show benign histological findings but some are indeterminate or non-diagnostic. In an attempt to separate out patients with a worse prognosis, Afirma has develoiped a proprietory tests, Benign Gene Expression Classifier.  In 2010, two modest-sized validation studies showed that the AGEC test could identify a benign gene expression signature in indeterminate cytology thyroid FNA samples with a negative prvaluations of the test have been positive. Palmetto Government Benefits Administrators (Palmetto GBA), the CMS Medicare Administrative Contractor with oversight for the Afirma GEC, has published its assessment of the test as an update to its local coverage article on molecular diagnostics. This review determined that the test meets criteria for analytical and clinical validity, and clinical utility as a reasonable and necessary Medicare benefit, effective January 1, 2012.25. As part of the CLIA Laboratory licensure process, the analytical and clinical validation data for the Afirma GEC were independently assessed by reviewers from the California Department of Public Health and the New York State Department of Health.26,27 Both of these reviews resulted in a favorable licensure outcome.

The National Comprehensive Cancer Network (NCCN) thyroid carcinoma guidelines were updated in December, 2012 to state “Molecular diagnostics may be useful to allow reclassification of follicular lesions (follicular neoplasm or follicular lesion of undetermined significance) as more likely to be benign or more likely to be malignant…If molecular testing predicts a risk of malignancy comparable to the risk of malignancy seen with a benign FNA cytology (approximately 5% or less), consider observation.” The NCCN guidelines for abnormal gene/gene expression profile testing are associated with Level of Evidence 2A (lower level evidence, uniform NCCN consensus that the intervention is appropriate).  The new 2015 NCCN Guidelines indicate that, when a thyroid nodule fine needle aspiration (FNA) result is indeterminate using traditional cytopathology, which relies on microscope-based review, physicians should consider using molecular testing in lieu of diagnostic surgery, provided the test’s performance is similar in accuracy to a benign diagnosis using cytopathology. This uaypia (AUS/FLUS).

REFERENCES:

1. Ross D, Cooper SD, Mulder JE.  Diagnostic approach to and treatment of thyroid nodules.  UpToDate, February 2013.
2. Ali SZ, Fish SA, Lanman R, Randolph GW, Sosa JA.  Use of the Afirma Gene Expression Classifier for Preoperative Identification of Benign Thyroid Nodules with Indeterminate Fine Needle Aspiration Cytopathology.  PLoS Curr.  2013 Feb 11:5.
3. NC Guidelines:  Thyroid Carcinoma, 2012 and 2015
4. Daniel S. Duick et al, The Impact of Benign Gene Expression Classifier Test Results on the Endocrinologist–Patient Decision to Operate on Patients with Thyroid Nodules with Indeterminate Fine-Needle Aspiration Cytopathology, Thyroid. 2012 October; 22(10): 996–1001.
5. Erik K. Alexander, M.D., Giulia C. Kennedy, Ph.D., Zubair W. Baloch, M.D., Ph.D., Edmund S. Cibas, M.D., Darya Chudova, Ph.D., James Diggans, Ph.D., Lyssa Friedman, R.N., M.P.A., Richard T. Kloos, M.D., Virginia A. LiVolsi, M.D., Susan J. Mandel, M.D., M.P.H., Stephen S. Raab, M.D., Juan Rosai, M.D., David L. Steward, M.D., P. Sean Walsh, M.P.H., Jonathan I. Wilde, Ph.D., Martha A. Zeiger, M.D., Richard B. Lanman, M.D., and Bryan R. Haugen, M.D. Preoperative Diagnosis of Benign Thyroid Nodules with Indeterminate Cytology N Engl J Med 2012; 367:705-715August 23, 2012 J.
6. Larry Jameson, EDITORIAL Minimizing Unnecessary Surgery for Thyroid Nodules,, N Engl J Med 2012; 367:765-767August 23, 2012

5. Syed Z. Ali, etal, Use of the Afirma® Gene Expression Classifier for Preoperative Identification of Benign Thyroid Nodules with Indeterminate Fine Needle Aspiration Cytopathology, PLoS Curr. 2013 February 11;