Diagnostic performance of the second-generation molecular tests in the assessment of indeterminate thyroid nodules: A systematic review and meta-analysis

Lee, Esther; Terhaar, Samantha J.; McDaniel, Lea; Gorelik, Daniel; Gerhard, Eleanor F.; Chen, Chen; Ma, Yan; Joshi, Arjun S.; Goodman, Joseph; Thakkar, Punam

doi:10.1016/j.amjoto.2022.103394

Cited by 22 publications

(21 citation statements)

References 20 publications

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“…Unlike other meta-analyses of molecular markers, where only samples with histologic correlates are considered ( 21 , 22 ), we assume that unoperated ITNs with GSC-B results are true negative results, as is common in RW practice. This is a limitation as one cannot truly calculate test performance without final histology and disease prevalence ( 27 ).…”

Section: Discussionmentioning

confidence: 99%

“…A previously published meta-analysis by Vuong et al that included the Afirma GEC and GSC validation studies as well as 5 of the GSC postvalidation studies compared the respective performances and showed significantly improved performance of the Afirma GSC compared with the GEC ( 20 ). However, that analysis, as well as other recent meta-analyses of the Afirma GSC ( 21 , 22 ), combine the VS data and exclude unoperated molecular benign results, which is a methodological limitation to a real-world (RW) assessment of the test performance. The primary value of the Afirma GSC is to identify molecular benign lesions in ITN and allow conservative clinical follow-up.…”

mentioning

confidence: 99%

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Real-World Performance of the Afirma Genomic Sequencing Classifier (GSC)—A Meta-analysis

Nasr

Andrioli²,

Endo

et al. 2022

The Journal of Clinical Endocrinology &Amp; Metabolism

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Context The Afirma® GSC aids in risk stratifying indeterminate thyroid nodule cytology (ITN). The 2018 GSC validation study (VS) reported a sensitivity (SN) of 91%, specificity (SP) of 68%, positive predictive value (PPV) of 47%, and negative predictive value (NPV) of 96%. Since then, 13 independent real world (RW) post-validation studies have been published. Objective This study’s objective is to compare the RW GSC performance to the VS metrics. Methods Rules and assumptions applying to this analysis include: 1. At least one patient with molecular benign results must have surgery for that study to be included in SN, SP and NPV analyses. 2. Molecular benign results without surgical histology are considered true negatives (TN) (as are the molecular benign results with benign surgical histology) 3. Unoperated patients with suspicious results are either excluded from the analysis (observed PPV (oPPV) and observed SP (oSP)) or assumed as histology negatives (false positives - conservative PPV (cPPV) and conservative SP (cSP)) 4. NIFTP is considered malignant. Results In RW studies, the GSC demonstrates a SN, oSP, oPPV and NPV of 97%, 88%, 65%, 99% respectively, and conservative RW performance showed cSP of 80% and cPPV of 49%, all significantly higher than the VS save for SN and cPPV. There was also a higher benign call rate (BCR) of 67% in RW studies compared to 54% in the VS (p < 0.05). Conclusion RW data for the Afirma GSC demonstrates significantly better oSP and oPPV performance compared to the VS, indicating an increased yield of cancers for resected GSC suspicious nodules. The higher BCR likely increases the overall rate of clinical observation in lieu of surgery.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Real-World Performance of the Afirma Genomic Sequencing Classifier (GSC)—A Meta-analysis

Nasr

Andrioli²,

Endo

et al. 2022

The Journal of Clinical Endocrinology &Amp; Metabolism

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“…A retrospective analysis showed similar findings between Afirma GEC and ThyGenX/ThyraMIR 176 . A meta‐analysis comparing Thyroseq v3 and Afirma GSC found high sensitivity and no difference in diagnostic performance, and both tests show improvements in ruling out malignancy than their respective prior versions 177,178 . Of note, the commercial tests described are only available in select developed nations at a reasonable cost and the majority of validation studies have been carried out in the United States of America 179 .…”

Section: Molecular Testingmentioning

confidence: 79%

“…176 A meta-analysis comparing Thyroseq v3 and Afirma GSC found high sensitivity and no difference in diagnostic performance, and both tests show improvements in ruling out malignancy than their respective prior versions. 177,178 Of note, the commercial tests described are only available in select developed nations at a reasonable cost and the majority of validation studies have been carried out in the United States of America. 179 Distinct differences in prevalence of genetic alteration in specific populations have been described and is a critical consideration which choosing a commercially available test or designing one.…”

Section: Summary Of Molecular Assaysmentioning

confidence: 99%

Molecular testing in fine‐needle aspiration of thyroid nodules

McMurtry

Canberk

Deftereos

2022

Diagnostic Cytopathology

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Background Thyroid nodules are commonly faced by clinicians as palpable nodules or incidentally identified on imaging. Nodules that are found to be suspicious by imaging can be biopsied by fine needle aspiration, which can yield material for molecular testing to refine the diagnosis. Methods The current literature concerning molecular testing in thyroid nodules including available commercial assays was reviewed and summarized. Results/Conclusions Commonly encountered alterations include mutations in RAS, BRAF, TERT promoter, PTEN, and DICER1 as well as fusions of RET, ALK, PAX8‐PPARγ, and NTRK. This article provides a summary of these molecular alterations, commercially available molecular assays, and general considerations for thyroid epithelial malignancies and benign thyroid nodules.

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“…When tested on thyroid nodules categorized as AUS and FN/SFN, studies have shown that GSC has a BCR of 60.0%–78.0%, sensitivity of 94.0%–100%, specificity of 17.0%–94.0%, PPV of 41.0%–85.3%, and NPV of 96.0%–100%. For AUS (BSRTC category III) alone, the following ranges are noted: 59.0%–80.8% for BCR, 85.7%–100% for sensitivity, 24.0%–94.9% for specificity, 52.0%–80.0% for PPV, and 96.3%–100% for NPV 17–24 . The wide range in test performance may be related to many factors and/or study variations (e.g., prevalence of malignancy associated with the study cohorts, case selection criteria, cases countered as numerator and/or denominator for calculation of diagnostic parameters, etc.).…”

Section: Discussionmentioning

confidence: 99%

Performance of Afirma genomic sequencing classifier and histopathological outcome in Bethesda category III thyroid nodules: Initial versus repeat fine‐needle aspiration

Jin

Lew

Pantanowitz

et al. 2023

Diagnostic Cytopathology

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BackgroundThere is limited data comparing the performance of Afirma Genomic Sequencing Classifier (GSC) in thyroid nodules carrying an initial versus a repeat diagnosis of atypia of undetermined significance (AUS). This study reported an institutional experience in this regard.Materials and MethodsThis retrospective study included consecutive thyroid nodules that had an initial or a repeat AUS diagnosis and had a subsequent GSC diagnostic result (benign or suspicious) from 2017 to 2021. All nodules were followed by surgical intervention or by clinical and/or ultrasound monitoring. GSC's benign call rate (BCR), rate of histology‐proven malignancy associated with a suspicious GSC result, and diagnostic parameters of GSC were calculated and compared between the two cohorts (initial versus repeat AUS). Statistical significance was defined with a p‐value of <.05 for all analysis.ResultsA total of 202 cases fulfilled inclusion criteria, including 67 and 135 thyroid nodules with an initial and a repeat AUS diagnosis, respectively. BCR was 67% and 66% in initial and repeat AUS cohorts, respectively. Rate of histology‐proven malignancy associated with a suspicious GSC result were 22% and 24% in initial and repeat AUS cohorts, respectively. Compared with the repeat AUS cohort, the initial AUS cohort showed slightly lower sensitivity (83% vs. 100%), specificity (70% vs. 73%), PPV (23% vs. 24%), NPV (98% vs. 100%), and diagnostic accuracy (72% vs. 75%). Nevertheless, these differences did not reach statistical significance.ConclusionGSC demonstrated comparable performance in thyroid nodules with a repeat AUS diagnosis versus nodules with an initial AUS diagnosis.

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Diagnostic performance of the second-generation molecular tests in the assessment of indeterminate thyroid nodules: A systematic review and meta-analysis

Cited by 22 publications

References 20 publications

Real-World Performance of the Afirma Genomic Sequencing Classifier (GSC)—A Meta-analysis

Real-World Performance of the Afirma Genomic Sequencing Classifier (GSC)—A Meta-analysis

Molecular testing in fine‐needle aspiration of thyroid nodules

Performance of Afirma genomic sequencing classifier and histopathological outcome in Bethesda category III thyroid nodules: Initial versus repeat fine‐needle aspiration

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