Surgical Utility of Afirma: Effects of High Cancer Prevalence and Oncocytic Cell Types in Patients with Indeterminate Thyroid Cytology

Harrell, R. Mack; Bimston, David N.

doi:10.4158/ep13330.or

Cited by 138 publications

(141 citation statements)

References 7 publications

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“…There is a tendency for the Afirma GEC test to report a high percentage of benign Hürthle cell nodules as suspicious. 13,15,16,18,19 These studies indicate that the risk of malignancy for a suspicious Afirma result is lower for aspirates with Hürthle cell cytology (19%-23%) than for those without a prominent population of Hürthle cells.…”

Section: Afirma Gene Expression Classifiermentioning

confidence: 87%

“…The reported PPVs range from 14% to 57% in various studies, which largely limits its clinical utility to predict the risk of malignancy. [14][15][16][17] As pointed out by Marti et al, 14 the risk of malignancy really depends on each individual institution's prevalence of malignancy. Hürthle cell-rich lesions appear to represent another limitation to the Afirma GEC test.…”

Section: Afirma Gene Expression Classifiermentioning

confidence: 99%

“…However, a study performed in a community hospital-based thyroid surgery practice showed a lower NPV (89.6%) than other studies in the literature. 16 The Afirma GEC test is expected to provide the most useful information in a practice setting with a prevalence of malignancy in indeterminate thyroid lesions of 15% to 21%. In this environment, the performance characteristics would be predicted to approximate those reported in the validation study.…”

Section: Afirma Gene Expression Classifiermentioning

confidence: 99%

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Molecular Testing of Thyroid Nodules: A Review of Current Available Tests for Fine-Needle Aspiration Specimens

Zhang

Lin²

2016

Archives of Pathology &Amp; Laboratory Medicine

100

158

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Context.— Fine-needle aspiration of thyroid nodules is a reliable diagnostic method to determine the nature of thyroid nodules. Nonetheless, indeterminate cytology diagnoses remain a diagnostic challenge. The development of multiplex molecular techniques and the identification of genetic alterations associated with different follicular cell–derived cancers in the thyroid have led to the introduction of several commercially available tests. Objective.— To summarize the most common commercially available molecular testing in thyroid cancer, focusing on the technical features and test performance validation. Data Sources.— Peer-reviewed original articles, review articles, and published conference abstracts were reviewed to analyze the advantages and limitations of the most common tests used in the evaluation of thyroid needle aspirations. Conclusions.— The most common tests available include the Afirma Gene Expression Classifier, ThyGenX, and ThyroSeq. The excellent negative predictive value (NPV) of the Afirma test allows it to be used as a “rule out” test. ThyGenX analyzes a panel of DNA mutations and RNA translocation fusion markers to assess the risk of malignancy with good NPV and positive predictive value. ThyroSeq is a next-generation sequencing–based gene mutation and fusion test that has been reported to have the best NPV and positive predictive value combined, suggesting that it can be used as a “rule in” and “rule out” test. Molecular testing of cytology specimens from thyroid nodules has the potential to play a major role in the evaluation of indeterminate thyroid lesions.

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Section: Afirma Gene Expression Classifiermentioning

confidence: 87%

Section: Afirma Gene Expression Classifiermentioning

confidence: 99%

Section: Afirma Gene Expression Classifiermentioning

confidence: 99%

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Molecular Testing of Thyroid Nodules: A Review of Current Available Tests for Fine-Needle Aspiration Specimens

Zhang

Lin²

2016

Archives of Pathology &Amp; Laboratory Medicine

100

158

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“…However, this finding needs further independent and prospective validation, and these results probably would be insufficient to avoid surgery if a mutation is not identified. However, despite having a lower risk of malignancy than other follicular neoplasms, 65-90% of HCNs are classified as suspicious by Afirma (22,23). Although the NPV in benign HCN by Afirma seems to be preserved, the cost-effectiveness in this setting is significantly challenged.…”

Section: Discussionmentioning

confidence: 99%

Institutional prevalence of malignancy of indeterminate thyroid cytology is necessary but insufficient to accurately interpret molecular marker tests

Valderrábano¹,

Leon

Centeno

et al. 2016

European Journal of Endocrinology

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Objective: Several molecular marker tests are available to refine the diagnosis of thyroid nodules. Knowing the true prevalence of malignancy (PoM) within each cytological category is considered necessary to select the most appropriate test and to interpret results accurately. We describe our institutional PoM among cytological categories and report our experience with molecular markers. Design: Single-center retrospective study. Methods: We calculated the institutional PoM for each category of the Bethesda system (Bethesda) on all thyroid nodules with cytological evaluation from October 2008 to May 2014. We estimated the predictive values for Afirma, miRInform, and ThyroSeq v2, based on published sensitivity and specificity. Finally, we assessed our own experience with miRInform. Results: The PoMs for Bethesda III and IV categories were 21 and 28%, respectively. ThyroSeq v2 achieves the highest theoretical negative and positive predictive values (NPV and PPV) in Bethesda III (98 and 75%) and Bethesda IV categories (96 and 83%). At our institution, miRInform detected a mutation in 16% of 109 indeterminate nodules tested, all in Bethesda IV specimens. Histology was available in 56 (51%) nodules. The observed sensitivity and specificity in Bethesda IV specimens were 63 and 86%, yielding an NPV and a PPV of 75 and 77%, respectively. Conclusions: For our current Bethesda III and IV PoM, the actual performance of miRInform was worse than expected. Theoretically ThyroSeq v2 should have the best performance, but it could be affected in the same way as miRInform, given the similarities between the tests. Assessing the institutional performance of each test is necessary along with PoM individualization.

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“…62 Possibly because of this, Afirma classifies 90% of the Hürthle cell neoplasms as "suspicious," even despite the fact that the ROM in these tumors is typically lower than that for the overall Bethesda category IV group, resulting in a low PPV in these nodules. 42,43,63 In part, this likely reflects the fact that the training of the support vector machine that encodes the proprietary algorithm included a number of Hürthle cell carcinomas but almost no benign Hürthle cell adenomas; as a consequence, the gene expression classifier determines all Hürthle cell lesions as suspicious.…”

Section: Follicular Neoplasm (Oncocytic Variant) /Hürthle Cell Neoplasmmentioning

confidence: 99%

Molecular Assays in Cytopathology for Thyroid Cancer

et al. 2015

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Background Despite lack of adequate, validated, independently performed clinical studies, several molecular tests are commercially available on the market and are being used on indeterminate thyroid nodules to guide patient-care decisions. Methods We summarize the current evidence on the role and limitations of molecular tests used in combination with thyroid cytopathology to refine the presurgical diagnosis of thyroid nodules. Results The clinical performance of molecular tests depends on the pretest risk of malignancy within the specific cytological group being assessed. This risk is variable and should be assessed at each institution to optimize the selection of the molecular test and the interpretation of its results. Next-generation sequencing has increased the sensitivity of oncogene panels while maintaining high specificity. Tests assessing the gene expression pattern have shown promising results, with high sensitivity but low specificity. The impacts of molecular markers on clinical practice remains in flux and their effect on health care costs remains poorly understood. Conclusions Further large, independent, confirmatory, clinical validation studies and real-world, cost-effectiveness studies are necessary before the widespread adoption of these tests can be endorsed as standard of care.

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Surgical Utility of Afirma: Effects of High Cancer Prevalence and Oncocytic Cell Types in Patients with Indeterminate Thyroid Cytology

Cited by 138 publications

References 7 publications

Molecular Testing of Thyroid Nodules: A Review of Current Available Tests for Fine-Needle Aspiration Specimens

Molecular Testing of Thyroid Nodules: A Review of Current Available Tests for Fine-Needle Aspiration Specimens

Institutional prevalence of malignancy of indeterminate thyroid cytology is necessary but insufficient to accurately interpret molecular marker tests

Molecular Assays in Cytopathology for Thyroid Cancer

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