Long‐Term Outcomes of Thyroid Nodule AFIRMA GEC Testing and Literature Review: An Institutional Experience

Abstract

Objective To assess outcomes of thyroid nodules analyzed with the AFIRMA gene expression classifier (GEC) and to perform a comprehensive literature review. Study Design Retrospective analysis of patients with thyroid nodules who underwent AFIRMA GEC testing at our institution. Settings A tertiary care academic institution. Subjects and Methods We collected clinical outcomes for 416 thyroid nodules that were analyzed with AFIRMA GEC between 2011 and 2015, including long-term follow-up through 2019. We performed a comprehensive literature review. Results The resection rate for nodules with “suspicious” GEC results was 85% with a positive predictive value of 37%. The resection rate for nodules with “benign” GEC results was 24% with a negative predictive value of 90%. The prevalence of thyroid malignancy in patients with thyroid nodules with indeterminate cytology at our institution during this timeframe was 41%, thus lowering our negative predictive value. Mean follow-up duration for unresected nodules was 27.8 months. Our resection rates for nodules with “benign” GEC were among the highest reported in the literature. Conclusions Molecular marker testing of thyroid nodules with indeterminate cytology can aid in the surgical decision making by obviating the need for diagnostic surgery and/or guiding extent of resection. Patients with other indications for surgery may not benefit from such costly testing.

Diagnostic accuracy of Afirma gene expression classifier, Afirma gene sequencing classifier, ThyroSeq v2 and ThyroSeq v3 for indeterminate (Bethesda III and IV) thyroid nodules: a meta-analysis

“…The included studies had a total of 6490 FNAs with ITN cytology with molecular diagnostics (GEC, GSC, TSv2, and TSv3). The detailed characteristics of the included studies ( 9 , 10 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 ) are given in Supplementary Table 3. According to the QUADAS-2 tool ( 24 , 25 ), the methodological quality of the included trials was acceptable ( Fig.…”

Long‐term Follow‐up of Cytologically Indeterminate Thyroid Nodules Found Benign on Molecular Testing: A Validation Study

“…Valderrabano et al 16 performed a systematic review of 19 studies encompassing 2568 nodules. They found significant differences in the sensitivity and specificity of the molecular test using the correlation between benign call rate and PPV from the pooled independent studies as compared with the PPV of the initial study by Alexander et al 3 Other studies attempted to validate the NPV of molecular testing through eventual resection of benign ITNs and histopathologic diagnosis 17–21 . Many of these studies yielded less robust NPVs than the initial validation study: 83.3% in Noureldine et al 20 vs 94% in Alexander et al This variation called for further investigation into molecular testing and its role in influencing the clinical management of ITNs.…”

DIAGNOSIS OF ENDOCRINE DISEASE: Usefulness of genetic testing of fine-needle aspirations for diagnosis of thyroid cancer

“…Compounding this dilemma, currently available molecular tests lack long-term follow-up data which are necessary to clarify the malignancy risk of nodules diagnosed as benign without surgery, further limiting the generalizability of clinical validation data to local practice (24). The best available literature on longterm follow-up does not include specific ultrasound or specific clinical data for the 93% of initially unresected thyroid nodules in the study beyond the statement that they did not identify malignancy (54), and it is not yet possible to have long-term follow-up data for the newest versions of Afirma or ThyroSeq due to their recent release.…”