Gene expression classifier for the diagnosis of indeterminate thyroid nodules: a meta-analysis

Abstract

Prior studies demonstrate that a novel genomic test, the gene expression classifier (GEC), could identify a benign gene expression signature in those nodules with indeterminate cytology with a negative predictive value of greater than 95 %. Examine the performance of the AFIRMA gene expression classifier in predicting benign and malignant nodules in patients with cytologically indeterminate nodules. MEDLINE and EMBASE search for studies meeting eligibility criteria between January 1, 2005, and August 30, 2015. A total of 58 studies identified. After excluding duplicates, case reports, reviews, commentary, insufficient data, a total of seven studies selected for analysis. We combined individual patient data from seven studies that examined the GEC test for indeterminate thyroid nodules. The reference standard for determination of benign or malignant nodules was the histopathology of the thyroidectomy specimen. A QUADAS-2 report for all studies included in the final analysis was tabulated for risk of bias and applicability. The pooled sensitivity of the GEC was 95.7 % (95 % CI 92.2-97.9, I (2) value 45.4 %, p = 0.09), and the pooled specificity was 30.5 % (95 % CI 26.0-35.3, I (2) value 92.1 %, p < 0.01). Overall, the diagnostic odds ratio was 7.9 (95 % CI 4.1-15.1). Patients with benign GEC were not followed long enough to ascertain the actual false-negative rates of the index test. Our meta-analysis revealed a high pooled sensitivity and a low specificity for the AFIRMA-GEC test for indeterminate thyroid nodules. This makes it an excellent tool to rule out malignancy.

Biologic and Clinical Perspectives on Thyroid Cancer

“…Afirma, a proprietary gene-expression classifier with a high negative predictive value, is designed to identify benign nodules among those with inconclusive results on cytopathological testing. 24,25 Alternatively, next-generation sequencing of a panel of oncogenes and tumor-suppressor genes identifies nodules with mutations that have been associated with thyroid cancer, with high positive and negative predictive values. 26 These two tests appear to reduce the incidence of unnecessary surgery, although their reliability in various clinical-practice settings remains to be established.…”

Risk of malignancy and neoplasia predicted by three molecular testing platforms in indeterminate thyroid nodules on fine‐needle aspiration

“…Based on the initial validation studies, Afirma Thyroid FNA Analysis (GEC/GSC) garners strength by targeting genetic signatures and mRNA expression to exclude malignancy . Its high NPV and low PPV were promoted to foster its use as a rule‐out test . Since its release as a novel testing platform, several authors have investigated the utility of Afirma GEC and its performance in clinical practice .…”

“…Its high NPV and low PPV were promoted to foster its use as a rule‐out test . Since its release as a novel testing platform, several authors have investigated the utility of Afirma GEC and its performance in clinical practice . Single institutional studies and large meta‐analyses of data demonstrated a compelling reduction in the number of unnecessary surgical operations .…”

“…A nonoperative approach was deemed as a safe alternative to a diagnostic lobectomy by many clinicians . It has been suggested that Afirma GEC has greatly modified patient care …”

Molecular testing for thyroid nodules: Review and current state

“…Designed to lower patient morbidity and the cost of care by decreasing unnecessary surgery for benign thyroid nodules, the majority of studies have demonstrated the utility of the Afirma GEC, whereas others have questioned the actual cost‐benefit analysis of reflexively incorporating it into clinical care . Behind some of the various interpretations of the performance of the GEC are the inherent differences in agreement among thyroid cytopathologists .…”