Afirma Genomic Sequencing Classifier Performance in Young Patients with Cytologically Indeterminate Thyroid Nodules.

Abstract

The Afirma Genomic Sequencing Classifier (GSC) is validated in patients > 21 yrs. with a 96% negative predictive value (NPV) for malignancy when GSC-(B)enign. Afirma GSC has not been formally studied in patients <21 yrs. with indeterminate thyroid nodules (ITNs). To evaluate Afirma GSC in young patients with ITNs. Retrospective analysis of Afirma GSC testing. ITNs referred for molecular testing in a real-world setting. Forty-nine ITNs from 49 patients < 21 yrs. who had histopathology or two years' clinical follow-up data ascertained. none. Afirma GSC test performance. In 49 ITNs from patients ages 9-20 yrs. (median 18.5 [IQR 17.3-19.8]), 30 were GSC-B and 19 GSC-(S)uspicious, among which 14 (73.7%) were malignant (i.e., true positive, TP) and five (26.3%) were benign (i.e., false positive, FP). All 30 Afirma GSC-B cases were either histologically (n=9) or clinically benign (n=21) (i.e., true negative, TN). All 14 malignancies were GSC-S (sensitivity 100% [95% CI 77-100%]); 30/35 clinically or histologically benign cases were GSC-B (specificity 86% [95% CI 70-95%]). NPV for an Afirma GSC-B result was 100% [95% CI 88-100%]. Genomic alterations were not detected in the 30 GSC-B samples. Among the 14 malignant samples, there were 9 papillary thyroid carcinomas; 1 oncocytic carcinoma; 1 non-invasive follicular thyroid neoplasm with papillary-like nuclear features; and 3 follicular thyroid carcinomas. In young patients with ITN, the Afirma GSC demonstrated an excellent negative predictive value when defining a TN result by histology or clinical follow-up.