The Effect of Implementing Gene Expression Classifier on Outcomes of Thyroid Nodules with Indeterminate Cytology

Abstract

Thyroid nodules are classified into six cytological categories under the Bethesda classification system. Two of these categories, atypical of undetermined significance (AUS) and suspicious for a follicular neoplasm (SFN), are further labeled as "indeterminate" diagnosis. Starting in June, 2012, Kansas University-Wichita Endocrine clinic implemented Afirma® Gene Expression Classifier (AGEC) to evaluate the need for surgical resection of thyroid nodules in patients with an indeterminate diagnosis. Electronic medical records of patients who underwent thyroid nodule fine-needle aspiration from 2004-2014 were reviewed. The aim of this study was to find whether implementing AGEC was associated with decreased surgical recommendation rate, decreased cost, and increased incidence of thyroid malignancy diagnosed by surgery in patients with indeterminate diagnosis. A total of 299 consecutive patients' charts were screened. Sixty-one (20 %) patients had an indeterminate diagnosis. Out of these, 27 (44 %) patients underwent evaluation before and 34 (56 %) patients underwent evaluation after AGEC implementation, respectively. Surgical recommendation for patients with indeterminate finding decreased from 81.5 to 50 % (p = 0.01) after AGEC implementation. Surgical pathology was read as malignant in 20 and 85.7 % (p < 0.01) of patients before and after AGEC implementation, respectively. Primary cost-benefit estimate showed implementing AGEC has saved $1048/patient in medical evaluation and initial management of patients with indeterminate diagnosis. AGEC implementation has decreased the number of surgical recommendations, has lowered financial burden, and has increased incidence of thyroid malignancy diagnosed by surgical pathology in patients with indeterminate diagnosis of thyroid nodules.

Evaluation of 167 Gene Expression Classifier (GEC) and ThyroSeq v2 Diagnostic Accuracy in the Preoperative Assessment of Indeterminate Thyroid Nodules: Bivariate/HROC Meta-analysis

“…al. 14 2014 0.42 (0.32-0.51) 1.00 (0.29-1.00) Han et al 15 2014 0.45 (0.23-0.68) 0.00 (0.00-1.00) Lastra et al 16 2014 0.46 (0.31-0.61) 1.00(0.16-1.00) McIver et al 17 2014 0.16 (0.05-0.33) 0.75 (0.19-0.99) Celik et al 18 2015 0.59 (0.33-0.82) 1.00 (0.16-1.00) Noureldine et al 19 2015 0.42 (0.35-0.50) 0.83 (0.52-0.98) Yang et al 20 2015 0.57 (0.44-0.68) 1.00 (0.48-1.00) Zhu et al 21 2015 0.60 (0.26-0.88) 0.00 (0.00-1.00) Abeykoon et al 22 2016 0.86 (0.57-0.98) 0.00 (0.00-1.00) Chaudhary et al 23 2016 0.38 (0.27-0.50) 1.00 (0.63-1.00) Marti et al 6 2016 0.43 (0.30-0.56) 1.00 (0.59-1.00) Sacks et al 24 2016 0.33 (0.21-0.47) 1.00 (0.40-1.00) Witt et al 25 2016 0.40 (0.16-0.68) 0.00 (0.00-1.00) Wu et al 26 sequencing technology in fine-needle aspiration and tissue samples [17]. This method was superseded by a second, improved version of the assay (ThyroSeq v2) [27].…”

Extending expressed RNA genomics from surgical decision making for cytologically indeterminate thyroid nodules to targeting therapies for metastatic thyroid cancer

“…The performance of GEC testing in 210 nodules categorized as atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS; Bethesda category III) or suspicious for follicular neoplasm (SFN; Bethesda category IV), all of which subsequently had definitive surgical pathology diagnoses, demonstrated a test sensitivity of 90%, specificity of 52%, NPV of 94%, and positive predictive value (PPV) of 37% at a cancer prevalence of 24% . Subsequently, 28 real‐world clinical experience studies have cumulatively reported that only 13% of nodules with GEC benign results underwent surgical resection, a marked reduction compared with the historical treatment of patients with cytologically indeterminate thyroid nodules . In 26 of these studies, only 3% of nodules (50 of 1934 nodules) with GEC benign results were found to be malignant .…”

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 .…”

“…26,27 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. 8,[28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44] Behind some of the various interpretations of the performance of the GEC are the inherent differences in agreement among thyroid cytopathologists. 7 However, another concern is the lack of a true "gold standard" in the subsequent validation studies, for which very few of the GEC benign cases have histologic correlation.…”