Independent Comparison of the Afirma Genomic Sequencing Classifier and Gene Expression Classifier for Cytologically Indeterminate Thyroid Nodules

Angell, Trevor E.; Heller, Howard T.; Cibas, Edmund S.; Barletta, Justine A.; Kim, Matthew I.; Krane, Jeffrey F.; Marqusee, Ellen

doi:10.1089/thy.2018.0726

Cited by 80 publications

(75 citation statements)

References 34 publications

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“…To our knowledge to date, 6 independent studies have been reported at national conferences or have been published (Fig. ) . These real‐world experiences demonstrate that approximately two‐thirds of test results are classified as GSC benign, approximately two‐thirds of the GSC suspicious nodules are proven malignant or NIFTP, and two‐thirds of all tested patients go on to clinical observation in lieu of diagnostic surgery.…”

Section: Introductionmentioning

confidence: 99%

“…Using surgical histology when available and otherwise assuming that unoperated GSC benign nodules are truly benign, these 6 experiences demonstrate an actual GSC upper limit of NPV as 97% to 100%. Two centers have reported their experience among Hurthle cell–dominant AUS/FLUS and SFN nodules . Whereas historically approximately 1 of 5 GEC tests returned as benign, the GSC benign rate increased to 2 of 3 tests.…”

Section: Introductionmentioning

confidence: 99%

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

Ali

Siperstein

Sadow

et al. 2019

Cancer Cytopathology

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The Afirma Genomic Sequencing Classifier (GSC) is a rule‐out test for malignancy/noninvasive follicular thyroid neoplasms with papillary‐like nuclear features among patients with Bethesda category III/IV nodules, whereas the complimentary Xpression Atlas provides genomic insights from a curated panel of 511 genes among GSC suspicious and Bethesda category V/VI nodules. Together, they facilitate personalized treatment decisions based on genomic insights derived from the transcriptome of the biopsied target and extend the diagnostic and therapeutic reach of cytopathologists and fine‐needle aspiration biopsy sample collection.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Ali

Siperstein

Sadow

et al. 2019

Cancer Cytopathology

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“…Analysis of all 96 patients who underwent surgery revealed cancer prevalence of 45.8% (44/96) and assuming that non-operated patients were characterized by benign disease, cancer prevalence would have been 26.6% (44/165) (Figure 1). The analysis of two recent reports testing performance of Afirma GSC amongst patients with indeterminate thyroid nodules, who underwent surgery, revealed a similar cancer prevalence of 50-55% (32,33). The TRS-based NPV of 82% is significantly lower than reported in these studies NPV of 100%, while TRS-based PPV of 88% is significantly better than reported in these studies PPV of 50-60% (32,33).…”

Section: Discussionmentioning

confidence: 63%

“…The analysis of two recent reports testing performance of Afirma GSC amongst patients with indeterminate thyroid nodules, who underwent surgery, revealed a similar cancer prevalence of 50-55% (32,33). The TRS-based NPV of 82% is significantly lower than reported in these studies NPV of 100%, while TRS-based PPV of 88% is significantly better than reported in these studies PPV of 50-60% (32,33). Compared with Afirma GSC, in populations with cancer prevalence 50-59%, TRS may perform better in avoiding surgery for benign nodules but might be associated with higher risk of missing cancer.…”

Section: Discussionmentioning

confidence: 96%

“…An updated version of Afirma called Genomic Sequencing Classifier (GSC) was validated in 2018 with a reported sensitivity of 91% and a specificity of 68% (31). An independent comparison between Afirma GEC and GSC showed that the latter version has a higher benign call rate compared to the former, predominantly for Hürthle cell cytology (32). These findings were recently corroborated by another study, from a single academic tertiary center, that also reported an improvement in specificity and PPV of Afirma GSC, while maintaining high sensitivity and NPV (33).…”

Section: Discussionmentioning

confidence: 99%

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A Novel Risk Stratification System for Thyroid Nodules With Indeterminate Cytology—A Pilot Cohort Study

et al. 2020

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Background: Thyroid ultrasound (US), fine needle aspiration biopsy (FNAB), and molecular testing have been widely used to stratify the risk of malignancy in thyroid nodules. The goal of this study was to investigate a novel diagnostic approach for cytologically indeterminate thyroid nodules (ITN) based upon a combination of US features and genetic alterations. Methods:We performed a pilot cohort study of patients with ITN (Bethesda III/IV), who underwent surgical treatment. Based on standardized sonographic patterns established by the American Thyroid Association (ATA), each ITN received an US score (X US ), ranging between 0 and 0.9 according to its risk of thyroid cancer (TC). DNA and RNA were extracted from pathologic material, available for all patients, and subjected to Oncomine TM Comprehensive Assay v2 (OCAv2) next-generation sequencing. Each genetic alteration was annotated based on its strength of association with TC and its sum served as the genomic classifier score (X GC ). The total risk score (TRS) was the sum of X US and X GC . ROC curves were generated to assess the diagnostic accuracy of X US , X GC, and TRS. Results:The study cohort consisted of 50 patients (39 females and 11 males), aged 47.5 ± 14.8 years. Three patients were excluded due to molecular testing failure. Among the remaining 47 patients, 28 (59.6%) were diagnosed with TC. BRAFV600E was the most common mutation in papillary TC, PAX8-PPARG fusion was present in NIFTP, pathogenic variants of SLX4, ATM, and NRAS were found in Hürthle cell TC and RET mutations in medullary TC. The diagnostic accuracy of X GC and TRS was significantly higher compared with X US (88 vs. 62.5%, p < 0.001; 85.2 vs. 62.5%, p < 0.001, respectively). However, this increased accuracy was due to significantly better sensitivity (80.7 vs. 34.6%, p < 0.001; 84.6 vs. 34.6%, p < 0.001, respectively) without improved specificity (94.7 vs. 90%, p = 0.55; 85.7 vs. 90%, p = 0.63, respectively).Gomes-Lima et al. Scoring System for Indeterminate Thyroid NodulesConclusion: Molecular testing might not be necessary in ITN with high-risk US pattern (X US = 0.9), as specificity of TC diagnosis based on Xus alone is sufficient and not improved with molecular testing. OCAv2 is useful in guiding the management of ITN with low-to-intermediate risk US features (X US < 0.9), as it increases the accuracy of TC diagnosis.

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Effectiveness of Molecular Testing Techniques for Diagnosis of Indeterminate Thyroid Nodules

et al. 2021

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IMPORTANCE Approximately 20% of thyroid nodules display indeterminate cytology. Molecular testing can refine the risk of malignancy and reduce the need for diagnostic hemithyroidectomy.OBJECTIVE To compare the diagnostic performance between an RNA test (Afirma genomic sequencing classifier) and DNA-RNA test (ThyroSeq v3 multigene genomic classifier). DESIGN, SETTING, AND PARTICIPANTSThis parallel randomized clinical trial of monthly block randomization included patients in the UCLA Health system who underwent thyroid biopsy from August 2017 to January 2020 with indeterminate cytology (Bethesda System for Reporting Thyroid Cytopathology category III or IV). INTERVENTIONS Molecular testing with the RNA test or DNA-RNA test. MAIN OUTCOMES AND MEASURES Diagnostic test performance of the RNA test compared with the DNA-RNA test. The secondary outcome was comparison of test performance with prior versions of the molecular tests. RESULTS Of 2368 patients, 397 were eligible for inclusion based on indeterminate cytology, and 346 (median [interquartile range] age, 55 [44-67] years; 266 [76.9%] women) were randomized to 1 of the 2 tests. In the total cohort assessed for eligibility, 3140 thyroid nodules were assessed, and 427 (13.6%) nodules were cytologically indeterminate. The prevalence of malignancy was 20% among indeterminate nodules. The benign call rate was 53% (95% CI, 47%-61%) for the RNA test and 61% (95% CI, 53%-68%) for the DNA-RNA test. The specificities of the RNA test and DNA-RNA test were 80% (95% CI, 72%-86%) and 85% (95% CI, 77%-91%), respectively (P = .33); the positive predictive values (PPV) of the RNA test and DNA-RNA test were 53% (95% CI, 40%-67%) and 63% (95% CI, 48%-77%), respectively (P = .33). The RNA test exhibited a higher PPV compared with the prior test version (Afirma gene expression classifier) (54% [95% CI, 40%-67%] vs 38% [95% CI, 27%-48%]; P = .01). The DNA-RNA test had no statistically significant difference in PPV compared with its prior version (ThyroSeq v2 next-generation sequencing) (63% [95% CI, 48%-77%] vs 58% [95% CI, 43%-73%]; P = .75). Diagnostic thyroidectomy was avoided in 87 (51%) patients tested with the RNA test and 83 (49%) patients tested with the DNA-RNA test. Surveillance ultrasonography was available for 90 nodules, of which 85 (94%) remained stable over a median of 12 months follow-up.CONCLUSIONS AND RELEVANCE Both the RNA test and DNA-RNA test displayed high specificity and allowed 49% of patients with indeterminate nodules to avoid diagnostic surgery. Although previous trials demonstrated that the prior version of the DNA-RNA test was more specific than the prior version of the RNA test, the current molecular test techniques have no statistically significant difference in performance.

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Independent Comparison of the Afirma Genomic Sequencing Classifier and Gene Expression Classifier for Cytologically Indeterminate Thyroid Nodules

Cited by 80 publications

References 34 publications

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

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

A Novel Risk Stratification System for Thyroid Nodules With Indeterminate Cytology—A Pilot Cohort Study

Effectiveness of Molecular Testing Techniques for Diagnosis of Indeterminate Thyroid Nodules

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