Afirma

Afirma Thyroid FNA Analysis

The Comprehensive Solution for Improved Thyroid Nodule Assessment

An Unmet Clinical Need is Addressed

Approximately 525,000 thyroid nodule fine needle aspiration (FNA) procedures were performed in the United States in 2011.1 FNA samples can be challenging to interpret and produce indeterminate results in 15% to 30% of cases.2

Prior to Afirma, guidelines recommended that most of these patients undergo a diagnostic thyroid surgery to assess whether the nodules are benign or malignant.2,3 Approximately 70% to 80% of the time, the nodules prove to be benign for cancer by surgical pathology.4,5

The Afirma Gene Expression Classifier

The novel Gene Expression Classifier (GEC), the centerpiece of the Afirma Thyroid FNA Analysis, helps physicians reduce the number of avoidable surgeries by preoperatively identifying benign nodules among those that were originally classified by cytopathology as indeterminate. The GEC measures the expression of 142 genes to determine if the FNA sample is benign or suspicious for cancer -- enabling patients with benign results to potentially avoid unnecessary surgery.

Clinical usage of the GEC is supported by mutiple, peer-reviewed, published studies and included in National Comprehensive Cancer Network (NCCN) and other leading clinical practice guidelines.6,7 The test is covered by Medicare and other major commercial payers, which collectively represent more than 135 million covered lives. Published evidence includes:

Clinical Validation

  • Alexander EK et al, New England Journal of Medicine, 20128– This prospective, multicenter clinical validation study involved 49 academic and community sites. Our Gene Expression Classifier exhibited a negative predictive value, or NPV, of 95% for indeterminate results in the atypia or follicular lesion of undetermined clinical significance category (AUS/FLUS) and 94% for indeterminate results in the suspicious for follicular or Hürthle cell neoplasm category (SFN/SHN) and reclassified as benign over half of the true benign FNA samples that had indeterminate cytopathology diagnoses, which the authors defined to include any results suspicious for malignancy in addition to AUS/FLUS and SFN/SHN. The authors concluded that a benign GEC result has a post-test probability of malignancy that is similar to the probability for operated nodules with cytologically benign features on an FNA, making watchful waiting a safe and effective clinical option for these patients.
  • Chudova D, et al, Journal of Clinical Endocrinology & Metabolism, 20109– In this study, our FNA trained classifier exhibited an NPV of 96% on a modest sized test set of indeterminate FNA samples, demonstrating an NPV similar to operated nodules with benign FNA cytology. The authors concluded that the GEC performance and validation conducted on an independent validation set demonstrated a high enough specificity to reclassify over half of indeterminate FNAs as benign and that the observed NPV indicated that those nodules classified as benign by the GEC carry a similar risk of malignancy as a benign diagnosis by thyroid nodule FNA cytopathology alone.
Clinical Utility
  • Duick DS et al, Thyroid, 201210 – In this study, a cohort of 51 endocrinologists (46 community-based; 5 academic based) at 21 practice sites in 11 states completed case report forms on whether surgery was recommended for their Afirma benign patients. Of 368 unique patients (395 cytopathology indeterminate FNAs) for whom data was collected, physicians and patients opted for watchful waiting in lieu of diagnostic thyroid surgery 92.4% of the time when the GEC result reclassified the patient's indeterminate nodule as benign. Surgery was performed on only 7.6% (CI 5.1 to 10.8) of patients, compared to the 74% rate of surgery on indeterminate thyroid nodules previously reported by Thyroid in 2011, a 90% reduction in the decision to operate.
  • Alexander EK et al, Journal of Clinical Endocrinology & Metabolism, 201411 – The study followed patients a mean of 8.5 months post-diagnosis which demonstrated the durability of a GEC benign result to change patient care. GEC results significantly altered care outcomes with 11 out of 174 (6%) GEC benign patients that underwent surgery as compared to 121 out of 148 (82%) GEC suspicious patients that underwent surgery.

Cost-Effectiveness

  • Li H et al, Journal of Clinical Endocrinology & Metabolism, 201112 – Researchers modeled the direct cost savings of utilizing the GEC in clinical practice. They concluded that if the GEC were to be universally adopted in routine clinical practice in the United States, every year 74% fewer surgeries would be performed on patients with benign nodules that cytopathology would have classified as indeterminate. The cost savings estimate in this model was based on an estimated 14% rate of surgery on a GEC benign nodule, which rate is almost double the 7.6% and 6.3% subsequently reported in the studies published in Thyroid and the Journal of Clinical Endocrinology and Metabolism (Chudova et al) described above. Based on the rate of surgery on GEC benign nodules reported in Thyroid, this study found that each GEC test would save approximately $2,600.
Analytical Validation
  • Walsh PS et al, Journal of Clinical Endocrinology & Metabolism, 201213 –In this study, analytical sensitivity, analytical specificity, robustness, and quality control of the GEC were successfully verified, indicating its suitability for clinical use.

Afirma Begins with Specialized Cytopathology

The Afirma Thyroid FNA Analysis combines specialized cytopathology and the novel genomic testing for improved thyroid nodule diagnosis. Physicians submit to Veracyte thyroid nodule FNA samples collected in a single patient visit. Then, a thyroid cytopathology specialist at Thyroid Cytopathology Partners (TCP), an independent partner of Veracyte, performs cytopathology assessment of the thyroid nodule FNA sample under the microscope. If the cytopathology diagnosis is benign or malignant, the analysis is complete. Only when TCP's cytopathology diagnosis is indeterminate* (TCP’s indeterminate rate to date has been 14% to 17%)14 is the proprietary Gene Expression Classifier performed.

The TCP team reads thousands of cases each month, making them what we believe to be the largest thyroid-only cytopathology group.15 Their volume and specialization expose them to rare neoplasms, including medullary thyroid cancer, on a routine basis.16 In addition, they have implemented processes to ensure quality and consistency is maintained.15 Learn more about TCP at thyroidcytopath.com.

The Afirma Malignancy Classifiers

In May 2014, Veracyte introduced its Afirma Malignancy Classifiers to further establish the Afirma Thyroid FNA Analysis as a comprehensive tool for reducing unnecessary surgeries and healthcare costs.

  • Medullary thyroid cancer (MTC) is an aggressive type of thyroid cancer that is not definitively identified by cytopathology alone about half of the time.17
  • About 40% of patients with MTC do not undergo a total thyroidectomy with central neck dissection – the recommended treatment in current guidelines.2,18,19
  • As a result, many patients with MTC may subsequently undergo a “follow-up” surgery, once the presence of MTC becomes known.
  • The presence of the BRAF V600E gene mutation may also prompt surgeons to perform more extensive thyroid surgeries.

The Afirma Malignancy Classifiers comprise tests for MTC and to assess BRAF V600E gene mutation status, and are intended to provide physicians with preoperative information that can enable them to perform a more appropriate procedure the first time, potentially reducing the need for additional surgeries – and the risks and costs that accompany them.

A Comprehensive Approach to Thyroid Nodule Management

With the Afirma Thyroid FNA Analysis, physicians can collect one FNA sample in a single office visit to:

  • obtain a confident cytopathology diagnosis through TCP;
  • identify benign nodules among those deemed indeterminate by cytopathology using the Afirma GEC; and
  • use the Afirma Malignancy Classifiers to obtain further preoperative information about those patients headed to surgery.

Visit Afirma.com to Learn More

* Indeterminate includes Follicular Lesion of Undetermined Significance (FLUS)/Atypia of Undetermined Significance (AUS) and (suspicious for) Hürthle/Follicular Neoplasm.

1. Sosa JA, Hanna J, Lanman RB, Robinson KA, Ladenson PW. Increases in thyroid nodule fine needle aspirations, surgeries and diagnoses of thyroid cancer in the United States. American Association of Endocrine Surgeons 34th Annual Meeting, Apr 14-16, 2013. Chicago, Ill. (oral abstract).
2. Cooper DS, Doherty GM, Haugen BR, Kloos RT, Lee SL, Mandel SJ, et al. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid.2009;19:1167-1214.
3. Gharib H, Papini E, Paschke R, Duick DS, Valcavi R, Hegedüs L, et al. American Association of Clinical Endocrinologists, Associazione Medicie Endocrinologi, and European Thyroid Association medical guidelines for clinical practice for the diagnosis and management of thyroid nodules: executive summary of recommendations. Endocr Pract. 2010;16(S1):1-43.
4. Wang CC, Friedman L, Kennedy GC, Wang H, Kebebew E, Steward DL, et al. A Large Multicenter Correlation Study of Thyroid Nodule Cytopathology and Histopathology. Thyroid. 2011;21:243-251.
5. Lewis CM et al. Thyroid Fine-Needle Aspiration Biopsy: Variability in Reporting 2009 Thyroid 19(7) 717-722.
6. Version 2.2013, 12/21/12 © National Comprehensive Cancer Network. http://www.nccn.org/professionals/physician_gls/pdf/thyroid.pdf.
7. Ross DS, Cooper DS, Mulder JE. Diagnostic approach to and treatment of thyroid nodules. UpToDate 2013.
8. Alexander EK, et al. Preoperative Diagnosis of Benign Thyroid Nodules with Indeterminate Cytology. N Engl J Med. 2012;367:705-715.
9. Chudova D, Wilde JI, Wang ET, Wang H, Rabbee N, Egidio CM, et al. Molecular Classification of Thyroid Nodules Using High-Dimensionality Genomic Data. J Clin Endocrinol Metab. 2010;95:5296-5304.
10. Duick DS, 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. Published Online Ahead of Print. 2012.doi:10.1089/thy.2012.0180.
11. Alexander EK, Schorr M, Klopper J, et al. Multicenter clinical experience with the Afirma Gene Expression Classifier. J Clin Endocrinol Metab. 2014;99(1):119-125.
12. Li H, Robinson KA, Anton B, Saldanha IJ, Ladenson PW. Cost-Effectiveness of a Novel Molecular Test for Cytologically Indeterminate Thyroid Nodules. J Clin Endocrinol Metab. 2011;96:E1719-E1726.
13. Walsh PS, Wilde JI, Tom EY, et al. Analytical performance verification of a molecular diagnostic for cytology-indeterminate thyroid nodules. J Clin Endocrinol Metab. 2012;97(12):E2297-E2306.
14. Data on file at Thyroid Cytopathology Partners, 2014.
15. Data on file at Veracyte, Inc.
16. Kloos KT, O’Reilly K, Traweek ST, et al. Novel gene expression classifier raises pre-operative suspicion of thyroid cancer. [Poster 1332] 21st Annual Meeting and Clinical Congress of the American Association of Clinical Endocrinology, Philadelphia, PA. May 23-27, 2012.
17. Essig GF, Porter K, Schneider D, et al. Fine Needle Aspiration and Medullary Thyroid Carcinoma: The Risk of Inadequate Preoperative Evaluation and Initial Surgery when Relying Upon FNAB Cytology Alone. Endocr Pract 2013:1-27.
18. Panigrahi B, Roman SA, Sosa JA. Medullary thyroid cancer: are practice patterns in the United States discordant from American Thyroid Association guidelines? Ann Surg Oncol. 2010;17:1490-1498.
19. Esfandiari NH, Hughes DT, Yin H, Banerjee M, Haymart MR. The effect of extent of surgery and number of lymph node metastases on overall survival in patients with medullary thyroid cancer. J Clin Endocrinol Metab. 2014;99(2):448-454.

Afirma Thyroid FNA Analysis Description
Afirma Thyroid FNA Analysis is a diagnostic service provided by Veracyte, Inc. in South San Francisco, California, USA and Austin, Texas, USA for the assessment of thyroid nodules. Patient samples obtained through fine needle aspirate (FNA) biopsies are collected for both cytopathology assessment and gene expression testing. Initially, cytopathology assessment is conducted. If the cytopathology diagnosis is benign or nondiagnostic, Afirma testing is complete.

If the cytopathology diagnosis is indeterminate (includes Follicular Lesion of Undetermined Significance (FLUS)/Atypia of Undetermined Significance (AUS) and (suspicious for) Hurthle/ Follicular Neoplasm), the thyroid nodule is greater than or equal to 1 cm and the patient is 21 years or older, the Afirma Gene Expression Classifier (GEC) is performed. The Afirma GEC determines the expression profile of RNA isolated from the nodule to be benign or suspicious for malignancy.

If the Afirma GEC result is suspicious, Afirma MTC is performed and the physician has the option to order Afirma BRAF to determine the BRAF V600E mutation status. If the cytopathology diagnosis is suspicious for malignancy or malignant, the physician has the option to order Afirma MTC and /or Afirma BRAF to determine if the expression profile of RNA isolated from the nodule is positive for Medullary Thyroid Carcinoma (MTC) and/or the BRAF V600E mutation status respectively.

Clinical correlation of the Afirma result is recommended. The Afirma Gene Expression Classifier, Afirma MTC and Afirma BRAF and their performance characteristics were determined by Veracyte. Afirma testing is used for clinical purposes. The Veracyte laboratory is certified under the Clinical Laboratory Improvement Amendments of 1988 (CLlA) as qualified to perform high-complexity clinical testing.