Afirma Genomic Sequencing Classifier Experience among the First 1614 Consecutive Samples from Cytologically Indeterminate Thyroid Nodules

Presentation Number: SAT-659
Date of Presentation: March 17, 2018, 2018

Michael Howard Shanik, MD1, Trevor E. Angell, MD2, Joshua Barbiarz, PhD3, Neil M. Barth, MD3, Thomas C. Blevins, MD4, Quan-Yang Duh, MD5, Ronald Ghossein, MD6, Richard Mack Harrell, MD7, Jing Huang, PhD3, Giulia Kennedy, PhD3, Su Yeon Kim, PhD3, Richard T. Kloos, MD3, Virginia Anne LiVolsi, MD8, Kepal N. Patel, MD9, Gregory W. Randolph, MD10, Peter M. Sadow, MD,PHD11, Julie Ann Sosa, MD12, Tom Traweek, MD13, Sean Walsh, MPH3, Michael W. Yeh, MD14, Paul W. Ladenson, MD15.
1Endocrine Associates of Long Island, PC, Smithtown, NY, USA, 2Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA, 3Veracyte, Inc., South San Francisco, CA, USA, 4Texas Diabetes and Endocrinology, Austin, TX, USA, 5University of California San Francisco, San Francisco, CA, USA, 6Memorial Sloan-Kettering Cancer Center, New York, NY, USA, 7The Memorial Center for Integrative Endocrine Surgery, Hollywood, FL, USA, 8University of Pennsylvania School of Medicine, Philadelphia, PA, USA, 9NYU Langone Medical Center, New York, NY, USA, 10Massachusetts Eye and Ear and Harvard Medical School, Boston, MA, USA, 11Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA, 12Duke Cancer Institute and Duke University Medical Center, Durham, NC, USA, 13Thyroid Cytopathology Partners, Austin, TX, USA, 14UCLA David Geffen School of Medicine, Los Angeles, CA, USA, 15Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Abstract

Background: The Afirma Genomic Sequencing Classifier (GSC) was designed to improve test specificity for identification of benign thyroid nodules among cytologically indeterminate lesions while maintaining high sensitivity for malignant nodules compared to its predecessor, the Gene Expression Classifier (GEC), with the goal of sparing more patients diagnostic surgery. The blinded GSC clinical validation performance was previously reported. Here we report the initial GSC experience since its July 26, 2017 introduction in a consecutive series of samples received by the Veracyte CLIA laboratory compared to the GEC experience. Methods: Veracyte analyzed the results of all Afirma GEC and GSC testing in Bethesda III and IV samples from January 1, 2011 through October 29, 2017. Results: The Afirma GEC was performed on 92089 Bethesda III and IV thyroid nodule samples. Considering adequate samples (85048, 92%), Afirma GEC was benign in 37794 (44%). Extrapolating from 25 published studies of 2136 GEC-tested patients in which only 11.6% of the GEC benign patients underwent surgery, we infer that 33410 patients may have been spared diagnostic surgery because of their GEC benign result, representing 39% of patients with adequate GEC samples. Since its introduction, the Afirma GSC was performed on 1614 Bethesda III and IV thyroid nodule samples. Considering adequate samples (1504, 93%), Afirma GSC was benign in 1103 (73%), and suspicious in 401 (27%). Thus, the GSC benign call rate was significantly higher than for the GEC (p <0.0002). Applying the reported operative rates for GEC benign patients to GSC benign patients, 65% of patients with adequate GSC samples may avoid surgery (p <0.0002 compared to GEC). Conclusion: While both the Afirma GEC and GSC have reliable benign results (i.e., high negative predictive values), the GSC provides significantly more benign results. This is likely to permit more clinical observation and less diagnostic surgery, reducing surgical complications, enhancing patients’ qualities of life, and decreasing healthcare expenditures.

Disclosures

  M.H. Shanik: Research Investigator; Self; Veracyte, Inc.. Speaker; Self; Veracyte, Inc.. T.E. Angell: None. J. Barbiarz: Employee; Self; Veracyte, Inc.. Stock Owner; Self; Veracyte, Inc. N.M. Barth: Employee; Self; Veracyte, Inc.. Stock Owner; Self; Veracyte, Inc. T.C. Blevins: Research Investigator; Self; Veracyte, Inc.. Speaker; Self; Veracyte, Inc.. Q. Duh: None. R. Ghossein: Consulting Fee; Self; Veracyte, Inc.. R.M. Harrell: None. J. Huang: Employee; Self; Veracyte, Inc.. Stock Owner; Self; Veracyte, Inc. G. Kennedy: Employee; Self; Veracyte, Inc.. Stock Owner; Self; Veracyte, Inc. S. Kim: Employee; Self; Veracyte, Inc.. Stock Owner; Self; Veracyte, Inc. R.T. Kloos: Employee; Self; Veracyte, Inc.. Stock Owner; Self; Veracyte, Inc. V.A. LiVolsi: Consulting Fee; Self; Veracyte, Inc. K.N. Patel: Speaker; Self; Veracyte, Inc.. G.W. Randolph: None. P.M. Sadow: Consulting Fee; Self; Veracyte, Inc. J.A. Sosa: Advisory Board Member; Self; American Thyroid Association Data Monitoring Committee of the Medullary Thyroid Cancer Consortium supported by GlaxoSmithKline, Novo Nordisk, Astra Zeneca and Eli Lilly. T. Traweek: Employee; Self; Thyroid Cytopathology Partners. Stock Owner; Self; Veracyte, Inc. S. Walsh: Employee; Self; Veracyte, Inc.. Stock Owner; Self; Veracyte, Inc.. M.W. Yeh: None. P.W. Ladenson: Consulting Fee; Self; Veracyte, Inc.. Research Investigator; Self; Veracyte, Inc.. Speaker; Self; Veracyte, Inc..