ThyroSeq v2 Testing: Impact on Cytologic Diagnosis, Management, and Cost of Care in Patients with Thyroid Nodule

Fazeli, Shoreh; Zehr, Bradely; Amraei, Razie; Toraldo, Gianluca; Guan, Haixia; Kindelberger, David W.; Lee, Stephanie L.; Cerda, Sandra

doi:10.1089/thy.2019.0191

Cited by 19 publications

(27 citation statements)

References 23 publications

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“…Based on the readings of the full-text articles, we excluded 28 articles for the following reasons: only enrolled nodules with benign test results (n = 4) ( 78 – 81 ) or suspicious test results (n = 1) ( 82 ), evaluated nodules with benign or malignant cytology (n = 2) ( 83 , 84 ), did not perform surgery and consequently did not provide reference standard in nodules with benign test results (n = 7) ( 85 – 91 ), an overlap of the participants with other studies (n = 8) ( 92 – 99 ), used freshly collected FNA samples as the reference standard (n = 1) ( 100 ), unavailable statistical analysis (n = 4) ( 13 , 22 , 101 , 102 ), and unavailable full-text article (n = 1). Finally, 40 articles met initial eligibility criteria and were systematically reviewed and abstracted.…”

Section: Resultsmentioning

confidence: 99%

“…Almost all records scored an unclear risk of bias for the “Index test” domain as they did not report whether the molecular panel was interpreted without knowledge of the histopathological diagnosis ( 17 , 20 , 30 , 32 , 35 , 38 , 41 – 44 , 46 – 50 , 53 – 57 , 59 – 61 , 103 ). The overall risk of bias concerning the reference standard was labeled as unclear because most of the studies but nine ( 13 , 14 , 29 – 31 , 35 , 45 , 49 , 104 ) have poorly described whether the evaluators were blind to the index test results. The risk of bias for studies flow and timing was set as high as in just 13 of 50 assessments reference standard was available in all the enrolled patients ( 11 , 14 – 16 , 21 , 23 , 60 , 62 , 65 , 67 , 68 , 71 ).…”

Section: Resultsmentioning

confidence: 99%

“…Thyroseq v3 indicates a PLR of 2.8 (95% CI: 1.2-6.3) and NLR of 0.02 [0.00-2.69], as displayed in Table 2. Additionally, we revealed a high DOR with a large 95% CI [157 (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)723)]. The area under the SROC curve was 0.95 (95% CI: 0.93-0.97; Supplementary Figure 1).…”

Section: Diagnostic Performance Of Thyroseq V3mentioning

confidence: 94%

“…ThyroSeq v2, replaced in 2011 the so-called seven-gene panel (BRAF, RAS, RET/PTC, and PAX8/PPAR) and queried 56 genes for point mutations, fusions, and abnormal gene expression. Its initial validation study claimed the potential for use as an all-around test of malignancy in ITNs given the reported positive predictive value (PPV) of 83% ( 13 ).…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Thyroseq v3, Afirma GSC, and microRNA Panels Versus Previous Molecular Tests in the Preoperative Diagnosis of Indeterminate Thyroid Nodules: A Systematic Review and Meta-Analysis

et al. 2021

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BackgroundMolecular tests are being used increasingly as an auxiliary diagnostic tool so as to avoid a diagnostic surgery approach for cytologically indeterminate thyroid nodules (ITNs). Previous test versions, Thyroseq v2 and Afirma Gene Expression Classifier (GEC), have proven shortcomings in malignancy detection performance.ObjectiveThis study aimed to evaluate the diagnostic performance of the established Thyroseq v3, Afirma Gene Sequencing Classifier (GSC), and microRNA-based assays versus prior iterations in ITNs, in light of “rule-in” and “rule-out” concepts. It further analyzed the impact of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) reclassification and Bethesda cytological subtypes on the performance of molecular tests.MethodsPubmed, Scopus, and Web of Science were the databases used for the present research, a process that lasted until September 2020. A random-effects bivariate model was used to estimate the summary sensitivity, specificity, positive (PLR) and negative likelihood ratios (NLR), and area under the curve (AUC) for each panel. The conducted sensitivity analyses addressed different Bethesda categories and NIFTP thresholds.ResultsA total of 40 eligible studies were included with 7,831 ITNs from 7,565 patients. Thyroseq v3 showed the best overall performance (AUC 0.95; 95% confidence interval: 0.93–0.97), followed by Afirma GSC (AUC 0.90; 0.87–0.92) and Thyroseq v2 (AUC 0.88; 0.85–0.90). In terms of “rule-out” abilities Thyroseq v3 (NLR 0.02; 95%CI: 0.0–2.69) surpassed Afirma GEC (NLR 0.18; 95%CI: 0.10–0.33). Thyroseq v2 (PLR 3.5; 95%CI: 2.2–5.5) and Thyroseq v3 (PLR 2.8; 95%CI: 1.2–6.3) achieved superior “rule-in” properties compared to Afirma GSC (PLR 1.9; 95%CI: 1.3–2.8). Evidence for Thyroseq v3 seems to have higher quality, notwithstanding the paucity of studies. Both Afirma GEC and Thyroseq v2 performance have been affected by NIFTP reclassification. ThyGenNEXT/ThyraMIR and RosettaGX show prominent preliminary results.ConclusionThe newly emerged tests, Thyroseq v3 and Afirma GSC, designed for a “rule-in” purpose, have been proved to outperform in abilities to rule out malignancy, thus surpassing previous tests no longer available, Thyroseq 2 and Afirma GEC. However, Thyroseq v2 still ranks as the best rule-in molecular test.Systematic Review Registrationhttp://www.crd.york.ac.uk/PROSPERO, identifier CRD42020212531.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Diagnostic Performance Of Thyroseq V3mentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

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Thyroseq v3, Afirma GSC, and microRNA Panels Versus Previous Molecular Tests in the Preoperative Diagnosis of Indeterminate Thyroid Nodules: A Systematic Review and Meta-Analysis

et al. 2021

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“…Reports on actual cost accounting after implementation of molecular testing have also suggested limited cost-effectiveness of this technology. A retrospective study reviewing the actual costs incurred after the implementation of molecular testing, for instance, have reported increased costs per patient ( 57 ). Applying modeling to real world data obtained retrospectively, Shapiro and colleagues demonstrated that while Afirma utilization could lead to a reduction in the absolute number of patients undergoing surgery (by 13%), its use led to increased overall cost per nodule ($2,399 higher compared to no molecular testing over 2 years) given that once classified as “suspicious” on molecular testing these nodules entailed further follow-up interventions (such as repeat biopsy down the road or surveillance imaging) ( 58 ).…”

Section: Cost-effectiveness Analysismentioning

confidence: 99%

Thyroid Nodule Molecular Testing: Is It Ready for Prime Time?

Khan

Zeiger

2020

Front. Endocrinol.

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Cytologically indeterminate thyroid nodules remain a diagnostic and clinical challenge, and molecular testing has been advocated and advanced as a diagnostic modality to help guide treatment. While studies have expounded on the improved diagnostic certainty with these tests, data demonstrating meaningful clinical impact and supporting their routine use is still limited at best. In this review, we discuss the limitations regarding diagnostic accuracy, impact on surgical decision-making and outcomes, and cost-effectiveness of molecular testing. By highlighting the limitations of these tests, we aim to promote more thoughtful utilization of these tools in the management of thyroid nodules going forward.

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Development of a Molecular Assay for Detection and Quantification of theBRAFVariation in Residual Tissue From Thyroid Nodule Fine-Needle Aspiration Biopsy Specimens

Chazen

MacMillan

et al. 2021

JAMA Netw Open

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IMPORTANCE Thyroid cancer, predominantly papillary thyroid carcinoma (PTC), is common, but an estimated 30% of ultrasonography-guided fine-needle aspiration (FNA) biopsies of thyroid nodules are indeterminate. BRAF variation, associated with poor clinicopathological characteristics, is a useful molecular marker for diagnostics. OBJECTIVETo develop a sensitive molecular assay for BRAF V600E detection in remaining tissue of thyroid FNA biopsies to identify patients with cancer carrying a BRAF variation. DESIGN, SETTING, AND PARTICIPANTSThis diagnostic study used tumor tissue from surgical formalin-fixed, paraffin-embedded (FFPE) specimens and residual tissue from thyroid FNA biopsies for genomic DNA extraction. FFPE specimens served as the validation set, and residual tissue from FNA biopsies served as the test set. A molecular assay was developed for accurate detection of BRAF V600E variation using locked nucleic acid (LNA) probe-based droplet digital polymerase chain reaction (dPCR), and the assay was validated by BRAF V600E immunohistochemical staining (IHC). The study was conducted between February 2019 and May 2021. RESULTS A total of 271 specimens, including 77 FFPE specimens (with a follow-up of 48 matched surgical specimens) and 146 residual FNA samples, were collected from 223 patients (mean [SD] age, 53.8 [15.3] years; 174 [78.0%] women; 49 [22.0%] men). The molecular assay by dPCR was first established to specifically and accurately detect and quantify wild-type BRAF and variant BRAF in DNA from human follicular thyroid carcinoma-derived FTC-133 and papillary thyroid carcinomaderived BCPAP cells. The linearity of quantification of BRAF V600E was calculated (y = 0.7339x;R 2 = 0.9996) with sensitivity at 0.02 copies/μL and reproducibility in detecting variant DNA at various dilutions(coefficient of variance in 0.3% DNA, 9.63%; coefficient of variance in 1.0% DNA, 7.41%). In validation testing, the dPCR assay and IHC staining exhibited 100% specificity in concordantly identifying BRAF V600E in PTCs (κ = 0.873; P < .001) and sensitivity of 32.0% (95% CI, 19.1% to 44.9%) in dPCR and 26.0% (95% CI, 13.1% to 38.9%) in IHC staining, with an improvement by 23.08% in dPCR compared with the IHC staining. The dPCR assay further detected BRAF V600E in 39 of 146 residual FNA specimens (26.7%). At short-term follow-up, 48 patients, including 14 of 39 patients with BRAF variation and 34 of 107 patients without BRAF variation on residual FNA specimens, underwent resection. The dPCR assay of BRAF status in the matched surgical specimens showed BRAF V600E variations in 12 patients and wild-type BRAF in 36 patients, with a high agreement to that in residual tissue of FNA specimens (κ = 0.789; P < .001). Among 14 patients with BRAF variations on residual FNA, 13 were diagnosed with PTC and 1 was diagnosed with anaplastic thyroid cancer at the thyroidectomy.

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ThyroSeq v2 Testing: Impact on Cytologic Diagnosis, Management, and Cost of Care in Patients with Thyroid Nodule

Cited by 19 publications

References 23 publications

Thyroseq v3, Afirma GSC, and microRNA Panels Versus Previous Molecular Tests in the Preoperative Diagnosis of Indeterminate Thyroid Nodules: A Systematic Review and Meta-Analysis

Thyroseq v3, Afirma GSC, and microRNA Panels Versus Previous Molecular Tests in the Preoperative Diagnosis of Indeterminate Thyroid Nodules: A Systematic Review and Meta-Analysis

Thyroid Nodule Molecular Testing: Is It Ready for Prime Time?

Development of a Molecular Assay for Detection and Quantification of theBRAFVariation in Residual Tissue From Thyroid Nodule Fine-Needle Aspiration Biopsy Specimens

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