Performance of the Afirma genomic sequencing classifier versus gene expression classifier: An institutional experience

Abstract

BACKGROUND:The use of fine-needle aspiration (FNA) to triage thyroid nodules has resulted in a significant reduction in thyroid surgery. However, approximately one-third of FNA specimens fall into the "indeterminate" category. The Afirma gene expression classifier (GEC) has been used to identify benign nodules with a high sensitivity and negative predictive value.However, the specificity and positive predictive value of the "suspicious" category are low. The updated Afirma genomic sequencing classifier (GSC) has been reported to demonstrate increased specificity while maintaining a high sensitivity and negative predictive value. METHODS: The authors retrospectively investigated 272 indeterminate thyroid FNA specimens (Bethesda categories III and IV) from nodules measuring >1 cm using the Afirma GEC or GSC tests (July 2012-January 2019). RESULTS: Of the 194 nodules tested using the Afirma GEC, a benign result was obtained in 88 cases (45.4%). In comparison, 52 of 78 FNA samples (66.7%) tested using GSC yielded a benign result (P = .002). In the GEC group, there were 31 cases with oncocytic cytology, 5 of which (16.1%) were benign on Afirma and 26 of which (83.9%) were suspicious on Afirma. In contrast, in the GSC group, there were 10 cases with oncocytic cytology, 8 of which (80%) were benign on Afirma and only 2 of which (20%) were found to be suspicious on Afirma (P < .001). The positive predictive value of the GSC group (57.1%) was higher than that of the GEC group (36.7%); however, there was no statistical significance noted (P = .15). CONCLUSIONS: A larger percentage of indeterminate thyroid FNA specimens were classified as benign using the Afirma GSC compared with the Afirma GEC, especially among samples with oncocytic features. The Afirma GSC appears to have a higher benign call rate compared with the Afirma GEC. Cancer Cytopathol 2019;127:720-724.

Molecular testing in diagnosis of indeterminate thyroid cytology: Trends and drivers

“…The PPV for GSC was found to be 57.1% compared to 36.7% for the GEC assay. 28 Similar results were reported by Endo et al in their comparative study between GEC and GSC. 29 Further studies with larger number of samples are required to validate Afirma GSC for clinical use in indeterminate thyroid nodules.…”

“…Results of meta-analyses of molecular panel testing for indeterminate thyroid nodules 28 Similarly, the PPV of ThyroSeq v2 fell from 42% if NIFTP was considered malignant to 33% when NIFTP was included in nonmalignant outcome. 34 Though pre-operative molecular testing might not assist in making a diagnosis of NIFTP, the presence of BRAF mutations or RET/-PTC translocations can aid in excluding this entity, thereby guiding better patient management.…”

“…The authors also reported that GSC was able to classify more oncocytic lesions as benign compared to the GEC. The PPV for GSC was found to be 57.1% compared to 36.7% for the GEC assay 28 . Similar results were reported by Endo et al in their comparative study between GEC and GSC 29 .…”

“…The main impact of introduction of NIFTP as a separate entity reflects on the performance characteristics of the existing molecular tests if NIFTP is not considered a carcinoma. For instance, if NIFTP was included in the malignant category, PPV of Afirma GEC would be 36.7% compared to 25.3% if NIFTP was not considered as malignant 28 . Similarly, the PPV of ThyroSeq v2 fell from 42% if NIFTP was considered malignant to 33% when NIFTP was included in non‐malignant outcome 34 …”

Thyroid Nodule Molecular Testing: Is It Ready for Prime Time?

“…This resulted in improved performance within specimens with Hürthle cell cytology, improved overall benign call rate of 68% ( vs. 41%) and a decrease in surgery rate from 48 to 35% for the population as a whole ( 36 ). Wei and colleagues have documented that the benign call rate for GSC is considerably higher than GEC (66.7 vs. 45.4%), and Endo and colleagues have reported a benign call rate of 88.8 vs. 25.7% for GSC vs. GEC for samples with Hürthle cells ( 37 , 38 ). Both these papers, as well as comparative study by Harrell and colleagues, suggested that the rate of surgical intervention was lower during the period when the newer test was utilized ( 39 ).…”