Comparison of Afirma GEC and GSC to Nodules Without Molecular Testing in Cytologically Indeterminate Thyroid Nodules

Abstract

Background Analysis of cytologically indeterminate thyroid nodules with Afirma Gene Expression Classifier (GEC) and Genomic Sequencing Classifier (GSC) can reduce surgical rate and increase malignancy rate of surgically resected indeterminate nodules. Methods Retrospective cohort analysis of all adults with cytologically indeterminate thyroid nodules from January 2013 through December 2019. We compared surgical and malignancy rates of those without molecular testing to those with GEC or GSC, analyzed test performance between GEC and GSC, and identified variables associated with molecular testing. Results 468 indeterminate thyroid nodules were included. No molecular testing was performed in 273, 71 had GEC, and 124 had GSC testing. Surgical rate was 68% in the group without molecular testing, 59% in GEC, and 40% in GSC. Malignancy rate was 20% with no molecular testing, 22% in GEC, and 39% in GSC (p = 0.022). GEC benign call rate (BCR) was 46%, sensitivity 100%, specificity 61% and PPV 28%. GSC BCR was 60%, sensitivity 94%, specificity 76%, and PPV 41%. Those with no molecular testing had larger nodule size, pre-operative growth of nodules, and constrictive symptoms, and those who underwent surgery in the no molecular testing group had higher BMI, constrictive symptoms, higher TIRADS and Bethesda classification. Type of provider was also associated with the decision to undergo surgery. Conclusion Implementation of GEC showed no effect on surgical or malignancy rate, but GSC resulted in significantly lower surgical and higher malignancy rates. This study provides insight into the factors that affect the real- world use of these molecular markers preoperatively in indeterminate thyroid nodules.

Facilitation of Definitive Cancer Diagnosis With Quantitative Molecular Assays of BRAF V600E and TERT Promoter Variants in Patients With Thyroid Nodules

“…Significant advances have been made in the understanding of cancer molecular pathogenesis, including genetic and epigenetic alterations . Molecular assays, such as real-time polymerase chain reaction (PCR) and next-generation sequencing (NGS), have arisen to detect genomic changes in tumors as novel cancer diagnostic approaches with great potential in the preoperative stratification of malignancy or benignity in thyroid nodules . Most cancer gene variants in most patients occur at intermediate frequencies (2%-20%) or lower .…”

Development and validation of an RNA sequencing–based classifier for medullary thyroid carcinoma on thyroid FNA

“…There have yet to be any false negatives or false positives. [24][25][26][27][28][29][30][31][32][33][34][35][36] In summary, the article by Randolph et al 11 provides insight into the development and validation of the Afirma RNA sequencing-based classifier for distinguishing MTC from non-MTC samples on thyroid FNAC. It presents a fascinating look into the complex process of machine learning and statistical models used to create such a test.…”

“…The Afirma RNA sequencing–based MTC classifier described in this text has also been performed on thyroid FNAC specimens from various independent institutions, with more than 2100 thyroid nodules reported in the literature. There have yet to be any false negatives or false positives 24–36 …”

Molecular diagnostics in the evaluation of thyroid nodules: Current use and prospective opportunities

“…The results showed (at a 24% cancer prevalence): SN -91% [CI, 79-98], SP -68% [CI, 60-76], NPV -96% [CI, [90][91][92][93][94][95][96][97][98][99], PPV -47% [CI, 36-58] (21) (Table 1). Since the validation study, 14 independent real-world studies have been published and in aggregate show a significant improvement in performance over the Afirma GEC, primarily with improved specificity and a higher benign call rate (BCR) of 65% (as compared to 54% with the Afirma GEC) (40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54). As expected, some of these studies have also demonstrated that the implementation of Afirma GSC reduced the rate of surgical intervention by 45-68% (40,43).…”