An Independent Study of a Gene Expression Classifier (Afirma) in the Evaluation of Cytologically Indeterminate Thyroid Nodules

McIver, Bryan; Castro, M. Regina; Morris, John C.; Bernet, Victor; Smallridge, Robert C.; Henry, Michael R.; Kosok, Laura; Reddi, Honey V.

doi:10.1210/jc.2013-3584

Cited by 202 publications

(227 citation statements)

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“…In an independent study, the sensitivity and specificity rates achieved by Afirma were reported to be 83% and 36%, respectively, and were the best rates of the case scenarios. 44 If lower sensitivity and specificity than anticipated are confirmed, then both predictive values would be negatively affected.…”

Section: Transcriptional Levelmentioning

confidence: 94%

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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Section: Transcriptional Levelmentioning

confidence: 94%

Molecular Assays in Cytopathology for Thyroid Cancer

et al. 2015

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“…The diagnostic performance of the GEC test was subsequently reported in 4 respective studies from the USA [29-32]. In each of these studies, treating physicians were aware of the GEC result at the time of surgical decision-making and not all patients who underwent a GEC test had gold-standard histopathological confirmation of the diagnosis; furthermore, there was no reported blinding of the histopathologists who ascertained the gold-standard diagnosis (when performed) [29-32].…”

Section: Should a Microarray Gec Test Be Routinely Used On An Indetermentioning

confidence: 99%

“…In each of these studies, treating physicians were aware of the GEC result at the time of surgical decision-making and not all patients who underwent a GEC test had gold-standard histopathological confirmation of the diagnosis; furthermore, there was no reported blinding of the histopathologists who ascertained the gold-standard diagnosis (when performed) [29-32]. McIver et al [29] reported in a prospective register study that patients at the Mayo Clinic (Rochester and Jacksonville sites) were offered the GEC test if the FNA was performed on site and the cytology was reported as SFN, suspicious for Hürthle cell neoplasm, or AUS/FLUS; approximately 83% (30/36) of the specimens included in the final analysis were SFN or suspicious for Hürthle cell neoplasm. In this study, criteria for offering GEC testing to patients with indeterminate cytology thyroid nodules included willingness of the patient to defer surgery, lack of compressive symptoms, and absence of higher-risk features (including head and neck radiation history, family history of thyroid cancer, prior history of thyroid cancer, or worrisome imaging characteristics) [29].…”

Section: Should a Microarray Gec Test Be Routinely Used On An Indetermentioning

confidence: 99%

European Thyroid Association Guidelines regarding Thyroid Nodule Molecular Fine-Needle Aspiration Cytology Diagnostics

Paschke¹,

Cantara²,

Crescenzi³

et al. 2017

Eur Thyroid J

135

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Molecular fine-needle aspiration (FNA) cytology diagnostics has the potential to address the inherent limitation of FNA cytology which is an indeterminate (atypia of undetermined significance/follicular lesion of undetermined significance follicular neoplasm) cytology. Because of the emerging role of molecular FNA cytology diagnostics, the European Thyroid Association convened a panel of international experts to review methodological aspects, indications, results, and limitations of molecular FNA cytology diagnostics. The panel reviewed the evidence for the diagnostic value of mutation panel assessment (including at least BRAF, NRAS, HRAS, KRAS, PAX8/PPARG, RET/PTC) of targeted next generation sequencing and of a microarray gene expression classifier (GEC) test in the diagnostic assessment of an indeterminate cytology thyroid nodule. Moreover, possible surgical consequences of molecular FNA diagnostic results of thyroid nodules and the evidence that analysis of a molecular FNA diagnostic panel of somatic mutations or a microarray GEC test can alter the follow-up were reviewed. Molecular tests may help clinicians to drive patient care and the surgical decision if the analysis is performed in specialized laboratories. These molecular tests require standardization of performance characteristics and appropriate calibration as well as analytic validation before clinical interpretation.

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“…The role of the GEC in cytologically indeterminate nodules that are SFM is less clear, and the test is not reflexively performed. Two recent reports with small sample sizes have independently evaluated GEC use in single-center studies, and the results emphasize the importance of cancer prevalence in interpretation of NPV and PPV (38,41). Harrell et al evaluated 35 patients with indeterminate cytology, histology, and GEC results, and had an observed cancer rate of 51%.…”

Section: Gecmentioning

confidence: 99%

American Thyroid Association Statement on Surgical Application of Molecular Profiling for Thyroid Nodules: Current Impact on Perioperative Decision Making

Ferris

Baloch

Bernet

et al. 2015

Thyroid

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Background: Recent advances in research on thyroid carcinogenesis have yielded applications of diagnostic molecular biomarkers and profiling panels in the management of thyroid nodules. The specific utility of these novel, clinically available molecular tests is becoming widely appreciated, especially in perioperative decision making by the surgeon regarding the need for surgery and the extent of initial resection. Methods: A task force was convened by the Surgical Affairs Committee of the American Thyroid Association and was charged with writing this article. Results/Conclusions: This review covers the clinical scenarios by cytologic category for which the thyroid surgeon may find molecular profiling results useful, particularly for cases with indeterminate fine-needle aspiration cytology. Distinct strengths of each ancillary test are highlighted to convey the current status of this evolving field, which has already demonstrated the potential to streamline decision making and reduce unnecessary surgery, with the accompanying benefits. However, the performance of any diagnostic test, that is, its positive predictive value and negative predictive value, are exquisitely influenced by the prevalence of cancer in that cytologic category, which is known to vary widely at different medical centers. Thus, it is crucial for the clinician to know the prevalence of malignancy within each indeterminate cytologic category, at one's own institution. Without this information, the performance of the diagnostic tests discussed below may vary substantially.

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An Independent Study of a Gene Expression Classifier (Afirma) in the Evaluation of Cytologically Indeterminate Thyroid Nodules

Cited by 202 publications

References 20 publications

Molecular Assays in Cytopathology for Thyroid Cancer

Molecular Assays in Cytopathology for Thyroid Cancer

European Thyroid Association Guidelines regarding Thyroid Nodule Molecular Fine-Needle Aspiration Cytology Diagnostics

American Thyroid Association Statement on Surgical Application of Molecular Profiling for Thyroid Nodules: Current Impact on Perioperative Decision Making

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