Abstract Context 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). Objective To evaluate Afirma GSC in young patients with ITNs. Design Retrospective analysis of Afirma GSC testing. Setting ITNs referred for molecular testing in a real-world setting Participants Forty-nine ITNs from 49 patients 21 yrs. who had histopathology or two years’ clinical follow-up data ascertained. Intervention none Main outcome measure Afirma GSC test performance Results 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. Conclusion 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.
Castellanos et al. (Wed,) studied this question.