Comparison of Afirma GEC and GSC to Nodules Without Molecular Testing in Cytologically Indeterminate Thyroid Nodules

Abstract Background Analysis of cytologically indeterminate thyroid nodules with Afirma Gene Expression Classifier (GEC) and Genomic Sequencing Classifier (GSC) can reduce surgical rate and increase malignancy rate of surgically resected indeterminate nodules. Methods Retrospective cohort analysis of all adults with cytologically indeterminate thyroid nodules from January 2013 through December 2019. We compared surgical and malignancy rates of those without molecular testing to those with GEC or GSC, analyzed test performance between GEC and GSC, and identified variables associated with molecular testing. Results 468 indeterminate thyroid nodules were included. No molecular testing was performed in 273, 71 had GEC, and 124 had GSC testing. Surgical rate was 68% in the group without molecular testing, 59% in GEC, and 40% in GSC. Malignancy rate was 20% with no molecular testing, 22% in GEC, and 39% in GSC (p = 0.022). GEC benign call rate (BCR) was 46%, sensitivity 100%, specificity 61% and PPV 28%. GSC BCR was 60%, sensitivity 94%, specificity 76%, and PPV 41%. Those with no molecular testing had larger nodule size, pre-operative growth of nodules, and constrictive symptoms, and those who underwent surgery in the no molecular testing group had higher BMI, constrictive symptoms, higher TIRADS and Bethesda classification. Type of provider was also associated with the decision to undergo surgery. Conclusion Implementation of GEC showed no effect on surgical or malignancy rate, but GSC resulted in significantly lower surgical and higher malignancy rates. This study provides insight into the factors that affect the real- world use of these molecular markers preoperatively in indeterminate thyroid nodules.

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Malignancy rate of atypia of undetermined significance/follicular lesion of undetermined significance in thyroid nodules undergoing FNA in a suburban endocrinology practice: A retrospective cohort analysis

Cancer Cytopathology ◽

10.1002/cncy.22054 ◽

2018 ◽

Vol 126 (10) ◽

pp. 881-888

Author(s):

Maighan A. Seagrove‐Guffey ◽

Haris Hatic ◽

Haoran Peng ◽

Kimberly C. Bates ◽

A. Ola Odugbesan

Keyword(s):

Retrospective Cohort ◽

Thyroid Nodules ◽

Cohort Analysis ◽

Malignancy Rate ◽

Retrospective Cohort Analysis ◽

Undetermined Significance

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Outcomes of Indeterminate Thyroid Nodules Managed Nonoperatively after Molecular Testing

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgaa887 ◽

2020 ◽

Author(s):

Catherine Y Zhu ◽

Ines Donangelo ◽

Deepashree Gupta ◽

Dalena T Nguyen ◽

Joana E Ochoa ◽

...

Keyword(s):

Thyroid Nodules ◽

False Negative ◽

False Negative Rate ◽

Molecular Testing ◽

Test Results ◽

Molecular Test ◽

Negative Rate ◽

Indeterminate Nodules

Abstract Context Molecular testing to refine the diagnosis of cytologically indeterminate thyroid nodules has become increasingly popular, but data on long-term durability of test results and the rate of delayed operation are limited. Objective Determine the delayed rate of surgical resection in indeterminate nodules with benign/negative molecular testing and the risk of false-negative molecular test results. Design Prospective follow-up of the Gene Expression Classifier vs Targeted Next-Generation Sequencing in the Management of Indeterminate Thyroid Nodules randomized controlled trial comparing the diagnostic test performance of Afirma Gene Expression Classifier and ThyroSeq v2. Setting University of California, Los Angeles. Participants Patients who underwent thyroid biopsy with indeterminate (Bethesda III/IV) cytology (April 2016 to July 2017). Intervention Ultrasound surveillance. Main Outcome Measure False-negative rate of molecular testing. Results Of 95 indeterminate nodules with negative/benign molecular test results, 12 nodules underwent immediate resection (11 benign nodules, 1 noninvasive follicular thyroid neoplasm nodule with papillary-like nuclear features). Nonoperative management was pursued for 83 (87.4%) nodules. The median surveillance was 26.7 months. Ten nodules were resected during surveillance and malignancy was identified in 4 nodules (overall false-negative rate of 5.8%). In the 4 malignant nodules that underwent delayed operation, surgery was prompted by sonographic changes during surveillance. Conclusions The majority of indeterminate nodules with negative molecular testing have a stable clinical course over 3 years of follow-up, but our finding of a 6% false-negative rate highlights the importance of continuing sonographic surveillance. Long-term studies are needed to determine the optimal length of follow-up.

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Update on Molecular Testing for Cytologically Indeterminate Thyroid Nodules

Archives of Pathology & Laboratory Medicine ◽

10.5858/arpa.2017-0174-ra ◽

2018 ◽

Vol 142 (4) ◽

pp. 446-457 ◽

Cited By ~ 37

Author(s):

Michiya Nishino ◽

Marina Nikiforova

Keyword(s):

Fine Needle Aspiration ◽

Test Performance ◽

Thyroid Nodules ◽

Needle Aspiration ◽

Molecular Testing ◽

Fine Needle ◽

Diagnostic Uncertainty ◽

Thyroid Cytology ◽

Molecular Tests ◽

Pubmed Search

Context.— Approximately 15% to 30% of thyroid nodules that undergo fine-needle aspiration are classified as cytologically indeterminate, presenting management challenges for patients and clinicians alike. During the past several years, several molecular tests have been developed to reduce the diagnostic uncertainty of indeterminate thyroid fine-needle aspirations. Objective.— To review the methodology, clinical validation, and recent peer-reviewed literature for 4 molecular tests that are currently marketed for cytologically indeterminate thyroid fine-needle aspiration specimens: Afirma, ThyroSeq, ThyGenX/ThyraMIR, and RosettaGX Reveal. Data Sources.— Peer-reviewed literature retrieved from PubMed search, data provided by company websites and representatives, and authors' personal experiences. Conclusions.— The 4 commercially available molecular tests for thyroid cytology offer unique approaches to improve the risk stratification of thyroid nodules. Familiarity with data from the validation studies as well as the emerging literature about test performance in the postvalidation setting can help users to select and interpret these tests in a clinically meaningful way.

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Real-world Comparison of Afirma GEC and GSC for the Assessment of Cytologically Indeterminate Thyroid Nodules

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgz099 ◽

2019 ◽

Vol 105 (3) ◽

pp. e428-e435 ◽

Cited By ~ 12

Author(s):

Vicente T San Martin ◽

Lima Lawrence ◽

James Bena ◽

Nabil Z Madhun ◽

Eren Berber ◽

...

Keyword(s):

Test Performance ◽

Predictive Value ◽

Preoperative Diagnosis ◽

Thyroid Nodules ◽

Gene Sequencing ◽

Surgical Excision ◽

Molecular Tests ◽

Academic Center ◽

Indeterminate Nodules ◽

Benign Nodules

Abstract Context Molecular tests have improved the accuracy of preoperative diagnosis of indeterminate thyroid nodules. The Afirma Gene Sequencing Classifier (GSC) was developed to improve the specificity of the Gene Expression Classifier (GEC). Independent studies are needed to assess the performance of GSC. Objective The aim was to compare the performance of GEC and GSC in the assessment of indeterminate nodules. Design, Settings, and Participants Retrospective analysis of Bethesda III and IV nodules tested with GEC or GSC in an academic center between December 2011 and September 2018. Benign call rates (BCRs) and surgical outcomes were compared. Histopathologic data were collected on nodules that were surgically resected to calculate measures of test performance. Results The BCR was 41% (73/178) for GEC and 67.8% (82/121) for GSC (P < .001). Among specimens with dominant Hürthle cell cytology, the BCR was 22% (6/27) for GEC and 63.2% (12/19) for GSC (P = .005). The overall surgery rate decreased from 47.8% in the GEC group to 34.7% in the GSC group (P = .025). One GEC-benign and 3 GSC-benign nodules proved to be malignant on surgical excision. GSC had a statistically significant higher specificity (94% vs 60%, P < .001) and positive predictive value (PPV) (85.3% vs 40%, P < .001) than GEC. While sensitivity and negative predictive value (NPV) dropped with GSC (97.0% vs 90.6% and 98.6% vs 96.3%, respectively), these differences were not significant. Conclusions GSC reclassified more indeterminate nodules as benign and improved the specificity and PPV of the test. These enhancements appear to be resulting in fewer diagnostic surgeries.

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Diagnostic Value of Molecular Testing in Sonographically Suspicious Thyroid Nodules

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa081 ◽

2020 ◽

Vol 4 (9) ◽

Author(s):

Maxwell M Wang ◽

Katrina Beckett ◽

Michael Douek ◽

Rinat Masamed ◽

Maitraya Patel ◽

...

Keyword(s):

Thyroid Nodules ◽

Medical Center ◽

Diagnostic Value ◽

Needle Aspiration ◽

Molecular Testing ◽

American Thyroid Association ◽

Indeterminate Nodules ◽

Thyroid Fine Needle Aspiration ◽

Indeterminate Cytology ◽

Risk Categories

Abstract Objective Molecular testing can refine the diagnosis for the 20% of thyroid fine-needle aspiration biopsies that have indeterminate cytology. We assessed the diagnostic accuracy of molecular testing based on ultrasound risk classification. Methods This retrospective cohort study analyzed all thyroid nodules with indeterminate cytology at an academic US medical center (2012-2016). All indeterminate nodules underwent reflexive molecular testing with the Afirma Gene Expression Classifier (GEC). Radiologists performed blinded reviews to categorize each nodule according to the American Thyroid Association (ATA) ultrasound classification and the American College of Radiology Thyroid Imaging, Reporting and Data System. GEC results and diagnostic performance were compared across ultrasound risk categories. Results Of 297 nodules, histopathology confirmed malignancy in 65 (22%). Nodules by ATA classification were 8% high suspicion, 44% intermediate, and 48% low/very low suspicion. A suspicious GEC result was more likely in ATA high-suspicion nodules (81%) than in nodules of all other ATA categories (57%; P = .04). The positive predictive value (PPV) of GEC remained consistent across ultrasound categories (ATA high suspicion, 64% vs all other ATA categories, 48%; P = .39). The ATA high-suspicion category had higher specificity than a suspicious GEC result (93% vs 51%; P < .01). A suspicious GEC result did not increase specificity for the ATA high-suspicion category. Conclusion The PPV of molecular testing remained consistent across ultrasound risk categories. However, a suspicious GEC result was very likely in ATA high-suspicion nodules and did not improve specificity in this sonographic category.

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MON-518 Institutional Experience with Cytologically Indeterminate Thyroid Nodules: No Molecular Testing Versus Afirma Gene Expression Classifier or Genomic Sequencing Classifier

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.1141 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Preethi Polavarapu ◽

Abbey Fingeret ◽

Ana Yuil-Valdes ◽

Anery Patel ◽

Whitney Goldner

Keyword(s):

Gene Expression ◽

Predictive Value ◽

Thyroid Nodules ◽

High Sensitivity ◽

Categorical Variables ◽

Genomic Sequencing ◽

Molecular Testing ◽

Continuous Variables ◽

Malignancy Rate ◽

Gene Expression Classifier

Abstract Background: Molecular analysis of indeterminate thyroid nodules has been shown to reduce unnecessary surgeries for benign thyroid nodules. Afirma Gene Expression Classifier (GEC) has a reported benign call rate (BCR) of 38-61%, and the newer generation Genomic Sequencing Classifier (GSC) has a reported BCR of 42-76%. Both GEC and GSC have a high sensitivity of 88-100% and negative predictive value (NPV) of 94-100%. Specificity and positive predictive value (PPV) have improved with GSC when compared to GEC, largely due to improvements in the classification of hurtle cell neoplasms. GSC PPV is reported as 47-76%. The aim of our study was to determine surgical and malignancy rates for patients at our institution with GEC, GSC, or for those who did not undergo molecular testing. Methods: Retrospective analysis of all Bethesda III and IV nodules with available follow up data at our institution between January 2013 and December 2018. We evaluated cytopathology, molecular testing with Afirma GEC or GSC, surgical rate, and malignancy rate between groups. Univariate descriptive statistics and bivariate analyses were calculated using Chi-squared and Fisher’s exact testing for categorical variables and one-way analysis of variance for continuous variables. Results: A total of 376 patients had Bethesda III and IV indeterminate thyroid nodule biopsies and met inclusion criteria for analysis. Of these, 262 patients did not undergo molecular testing, 50 underwent GEC, and 64 GSC testing. There was no difference between the groups for gender, age, or BMI. The overall surgical rate was 66.4, 60.0, and 46.9%, respectively (p=0.014). There was no difference in BCR for GEC or GSC with 44.0% versus 54.7% (p=0.38). There was no difference in malignancy rate with no molecular testing 19.5%, 22.7% if GEC suspicious, and 29.2% if GSC suspicious (p=0.619). GEC had a PPV of 22.7%, NPV of 100%, sensitivity of 100%, and specificity of 56.4% compared with GSC with PPV of 29.2%, NPV of 100%, the sensitivity of 100%, and specificity of 67.3%. Our overall rate of incidentally noted malignancy for indeterminate thyroid nodules who ultimately underwent surgery was 23 of 234 (9.9%). Conclusions: At our institution, the surgical rate was not different between patients who did not have molecular testing and those with GEC, however, there was a significant reduction in overall surgeries when using GSC. GSC BCR improved when compared to GEC, consistent with previous studies, but PPV remained low at 29.2%, which is lower than previously reported.

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Clinical Utility of Sonographic Features in Indeterminate Pediatric Thyroid Nodules

Acta Endocrinologica ◽

10.1530/eje-20-1480 ◽

2021 ◽

Author(s):

Danielle M. Richman ◽

Christine E. Cherella ◽

Jessica R. Smith ◽

Biren P. Modi ◽

Benjamin Zendejas ◽

...

Keyword(s):

Thyroid Nodules ◽

Needle Aspiration ◽

Risk Level ◽

Aspiration Cytology ◽

Malignancy Rate ◽

Risk Levels ◽

Malignancy Risk ◽

Indeterminate Nodules ◽

Needle Aspiration Cytology ◽

Indeterminate Cytology

Objective. Surgical resection is recommended for cytologically indeterminate pediatric thyroid nodules due to their intermediate malignancy risk. We evaluated the utility of ultrasound characteristics for refining malignancy risk to inform the management of these nodules. Design. Retrospective cohort study (2004-2019) Methods. We analyzed consecutive thyroid nodules with indeterminate fine-needle aspiration cytology (Bethesda category III, IV, or V) in pediatric patients (<19 years). We assessed the association of demographic and sonographic characteristics with malignancy risk among all indeterminate nodules and within each Bethesda category. Results. Eighty-seven cytologically indeterminate nodules were identified in 78 patients. Bethesda category was III in 56 nodules (64%), IV in 12 (14%), and V in 19 (22%). The malignancy rate was 46/87 (53%) overall, and 23/56 (41%), 8/12 (75%), and 15/19 (79%) in Bethesda III, IV, and V nodules, respectively. Malignancy rate was higher in solitary nodules (67% vs. 37%, p=0.004) and nodules with irregular margins (100% vs. 44%, p<0.001) or calcifications (82% vs. 43%, p=0.002). American College of Radiology Thyroid Imaging, Reporting and Data System (ACR TI-RADS) risk level TR5 was associated with a higher rate of malignancy than lower TI-RADS risk levels (80% vs. 42%, p=0.002). Within individual Bethesda categories, TI-RADS risk level was not associated with malignancy. No sonographic feature had a negative predictive value for malignancy greater than 80%. Conclusions. In pediatric thyroid nodules with indeterminate cytology, some sonographic features—including higher ACR TI-RADS risk level—are associated with malignancy, but these associations are unlikely to alter clinical management in most cases.

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Paediatric tele-emergency care: A study of two delivery models

Journal of Telemedicine and Telecare ◽

10.1177/1357633x19839610 ◽

2019 ◽

pp. 1357633X1983961

Author(s):

Paula A Weigel ◽

Kimberly AS Merchant ◽

Amy Wittrock ◽

Jamie Kissee ◽

Fred Ullrich ◽

...

Keyword(s):

Service Use ◽

Cohort Analysis ◽

Case Control ◽

Retrospective Cohort Analysis ◽

Key Characteristics ◽

Delivery Models ◽

Model Structures ◽

Ongoing Evaluation ◽

Paediatric Critical Care ◽

Insight Into

Introduction Tele-emergency models have been utilized for decades, with growing evidence of their effectiveness. Due to the variety of tele-emergency department (tele-ED) models used in practice, however, it is challenging to build standardized metrics for ongoing evaluation. This study describes two tele-ED programs, one specialized and one general, that provide care to paediatric populations. Through an examination of model structures and patient populations, we gain insight into how evaluative measures should reflect tele-ED model design and purpose. Methods Qualitative descriptions of the two tele-ED models are presented. We show a retrospective cohort analysis describing paediatric patients’ key characteristics, reasons for visit, and disposition status by case/control status. Case/control patient encounter data were collected October 2015 through December 2017 from 15 spoke hospitals within each tele-ED program. Results The two tele-ED models serve distinct paediatric populations, and measures of tele-ED utilization and disposition reflect those differences. In the specialized University of California (UC) Davis Health program, tele-ED was utilized in 36% of paediatric critical care encounters and 78% of those were transferred. In the Avera eCARE program, tele-ED was activated in 1.7% of paediatric encounters and 50.6% of those were transferred. When Avera eCARE paediatric encounters were stratified by severity, measures of tele-ED use and disposition status among high-severity encounters were more similar to UC Davis Health. Discussion This study describes how design choices of tele-ED models have implications for evaluative measures. Measures of tele-ED model success need to reflect model purpose, populations served, and for whom tele-ED service use is appropriate.

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ECMO Cannulation Criteria in COVID-19 (ECC-VID) and Obesity: A Literature Review and Retrospective Cohort Analysis

Surgical Case Reports ◽

10.31487/j.scr.2021.08.18 ◽

2021 ◽

pp. 1-5

Author(s):

Christina Creel-Bulos ◽

Brian Hassani ◽

Christina Creel-Bulos ◽

Michael Connor ◽

Mark Caridi-Schieble ◽

...

Keyword(s):

Acute Respiratory Distress Syndrome ◽

Retrospective Cohort ◽

Management Strategy ◽

Distress Syndrome ◽

Rescue Therapy ◽

Cohort Analysis ◽

High Survival ◽

Obese Patients ◽

Retrospective Cohort Analysis ◽

Insight Into

Veno-Venous Extracorporeal Membrane Oxygenation (V-V ECMO) continues to be used as rescue therapy for patients with acute respiratory distress syndrome (ARDS) secondary to coronavirus disease 2019 (COVID-19). Although there is emerging literature on the use of and mortality associated with V-V ECMO in the management of patients with COVID-19, our understanding of who may benefit from this management strategy remains limited. Our clinicians sought to provide further insight into pre-cannulation characteristics and mortality in a cohort of patients with COVID-19 associated ARDS managed with V-V ECMO that primarily consisted of obese patients (90%, n=18) with a BMI of 30 kg/m2 or greater. Our findings not only revealed high survival to hospital discharge (70%, n=14) but demonstrated non-inferior outcomes and survival in obese patients. With an imminent next wave of rising infections, knowledge of which patients have a better chance of survival with the initiation of V-V ECMO is essential. Obese patients have been historically underrepresented in ECMO outcomes literature, but our findings suggest the utilization of ECMO for COVID-19 associated ARDS in these patient subsets should be considered and outcomes should be further explored.

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