Risk of malignancy and neoplasia predicted by three molecular testing platforms in indeterminate thyroid nodules on fine‐needle aspiration

Partyka, Kristen L.; Trevino, Karen; Randolph, Melissa; Cramer, Harvey; Wu, Howard H.

doi:10.1002/dc.24250

Cited by 21 publications

(33 citation statements)

References 56 publications

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“…Regarding molecular panels, 25 studies evaluated the diagnostic performance of the Afirma GEC ( 8 , 16 , 17 , 40 , 47 – 54 , 56 – 58 , 61 , 63 , 64 , 66 – 70 , 72 , 76 , 77 ), and four articles reported the Afirma GSC ( 16 , 17 , 57 , 70 ). Thyroseq versions 2 and 3 were found in nine ( 11 , 15 , 58 , 59 , 61 , 62 , 71 , 73 , 75 ) and four papers ( 14 , 55 , 59 , 65 ), respectively, while ThyraMIR/ThyGenX ( 23 , 67 , 68 ) and ResettaGX Reveal ( 61 , 67 , 68 ) were explored in three studies, respectively. The panels with the fewest assessments were ThyraMIR/ThyGeNEXT and miRInform ( 23 , 74 ).…”

Section: Resultsmentioning

confidence: 99%

“…The majority of the studies (n = 32) evaluate a single molecular panel, of which 18 articles reported Afirma GEC alone ( 8 , 40 , 47 – 54 , 56 , 63 , 64 , 66 , 69 , 72 , 76 , 77 ), nine papers assessed second or third version of Thyroseq NGS ( 11 , 14 , 15 , 55 , 62 , 65 , 71 , 73 , 75 ) and lastly, ThyraMIR/ThyGeNEXT, ThyraMIR/ThyGenX, miRInform and RosettaGX Reveal were each approached in a study ( 21 , 23 , 60 , 74 ). Among the nine studies that measured up more that two molecular panels, four paper compared Afirma GEC and GSC ( 16 , 17 , 57 , 70 ), two manuscripts reported a comparison between Afirma GEC and Thyroseq v2 ( 58 , 61 ), two papers investigated the diagnostic performance of Afirma GEC, RosettaGX and Interpace MPT ( 67 , 68 ) and Jug et al. ( 59 ) compared the two last versions of Thyroseq NGS.…”

Section: Resultsmentioning

confidence: 99%

“…After surgical treatment, the histological assessment revealed 72 of 120 (60%) malignant tumors. A single NIFTP case with a positive RosettaGX result was recorded following histological assessment (68)…”

Section: Mirna-based Platforms: Rosettagx Reveal and Mirinformmentioning

confidence: 99%

“…Afirma Gene Expression Classifier; AGSC, Afirma Gene Sequencing Classifier; cPTC, classic papillary thyroid cancer; E-FVPTC, Encapsulated FVPTC; FVPTC, follicular variant of papillary thyroid cancer; FTC, follicular thyroid cancer; HC, Hurthle cell predominant; HCC, Hurthle cell carcinoma; I-FVPTC, Infiltrative FVPTC; MI, minim invasive; OVPTC, Oncocytic variant papillary thyroid cancer; MPT, Multiplatform Test (ThyraMIR/ThyGenX); MPTX, ThyraMIR/ThyGeNEXT; MTC, medullary thyroid cancer; N/A, Not available; NIFTP, Noninvasive follicular thyroid neoplasm with papillary like nuclear features; no., number; PDTC, poorly differentiated thyroid cancer; Pro, Prospective, PTC, Papillary thyroid cancer; Retro, Retrospective; TC, thyroid cancer; TQ2, ThyroseQ version 2; TQ3, ThyroseQ version 3.reported the Afirma GSC(16,17,57,70). Thyroseq versions 2 and 3 were found in nine(11,15,58,59,61,62,71,73,75) and four papers(14,55,59,65), respectively, while ThyraMIR/ ThyGenX(23,67,68) and ResettaGX Reveal(61,67,68) were explored in three studies, respectively. The panels with the fewest assessments were ThyraMIR/ThyGeNEXT and miRInform(23,74).…”

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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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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: Mirna-based Platforms: Rosettagx Reveal and Mirinformmentioning

confidence: 99%

mentioning

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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“…In contrast, some cytologists have introduced the term “risk of neoplasia” (RON) for thyroid FNA specimens . Using this measure, the identification of a neoplastic nodule (including follicular adenoma as well as carcinoma) rather than a hyperplastic nodule or normal thyroid tissue is counted as a “success.” Indeed, much of the literature that predated TBSRTC and the introduction of ROM was reported in just such a manner.…”

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confidence: 99%

Communicating risk for thyroid FNA: The pursuit of a better metric

Renshaw

Krane

2019

Cancer Cytopathology

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Communicating the clinical significance of cytologic findings is a vital function of any cytology report. One of the key goals of developing uniform reporting systems, such as The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC), 1 is to provide a reproducible framework for conveying the clinical significance of each diagnostic category (ie, the associated risk) to clinicians and patients. This risk data should be readily understood and applicable to subsequent clinical decision making. Recent developments in the management of patients with thyroid nodules increasingly recognize the complex nature of thyroid neoplasia, in which the vast majority of tumors, including most "cancers," pose little risk of patient mortality. 2 This more nuanced approach to the clinical management of thyroid cancers should be matched by a similarly nuanced conveyance of risk in cytology reports, particularly for those specimens exhibiting "indeterminate" (TBSRTC categories III-V) findings. The challenge of communicating this complexity forms the basis for this discussion.The most common way of reporting risk in thyroid fine-needle aspiration (FNA) is via the risk of malignancy (ROM). ROM initially was introduced to allow for the more accurate comparison of the performance of individual cytopathologists and laboratories for both quality assurance and research purposes. 3 ROM subsequently was incorporated into the first iteration of TBSRTC.

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Combining molecular testing and the Bethesda category III:VI ratio for thyroid fine‐needle aspirates: A quality‐assurance metric for evaluating diagnostic performance in a cytopathology laboratory

Gokozan

Dilcher

Alperstein

et al. 2021

Cancer Cytopathology

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Background Molecular testing (MT) of thyroid fine‐needle aspiration (FNA)‐derived genetic material is commonly used to assess malignancy risk for indeterminate cases. The Bethesda System for Reporting Thyroid Cytopathology (TBS) provides limited guidance for the appropriate use of category III (atypia of undetermined significance [AUS]). The authors combined MT with cytomorphology to monitor AUS diagnoses in a cytopathology laboratory. Methods Neoplasia‐associated genetic alterations (NGAs) were determined by MT of preoperative FNA biopsies or resected malignancies and were categorized as BRAF V600E mutations, RAS‐like mutations (HRAS, NRAS, or KRAS mutations or non‐V600E BRAF mutations), or other mutations. Results Among 7382 thyroid FNA biopsies, the AUS rate was 9.3% overall and ranged from 4.3% to 24.2% among 6 cytopathologists (CPs) who evaluated >150 cases. The ratio of specimens falling into TBS category III to specimens falling into category VI (malignant) (the III:VI ratio) was 2.4 overall (range, 1.1‐8.1), and the ratio of specimens falling into TBS categories III and IV (follicular neoplasm or suspicious for follicular neoplasm) combined (III+IV) to specimens falling into category VI (the [III+IV]:VI ratio) was 2.9 overall (range, 1.4‐9.5). MT was performed on 588 cases from 560 patients (79% women) with a median age of 56 years (range, 8‐89 years). BRAF V600E mutation was the most common (76% of cases) in TBS category VI and was rare (3%) in category III. RAS‐like mutations were most common in TBS categories III (13%), IV (25%), and V (suspicious for malignancy) (17.5%). The NGA rate in AUS cases fell between 5% and 20% for 5 of 6 CPs and did not correlate with the III:VI ratio or the (III+IV):VI ratio. Conclusions Lack of correlation between the NGA rate and easily calculable diagnostic ratios enables the calibration of diagnostic thresholds, even for CPs who have normal metrics. Specifically, calculation of the NGA rate and the III:VI ratio may allow individual CPs to determine whether they are overcalling or undercalling cases that other CPs might otherwise recategorize.

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Risk of malignancy and neoplasia predicted by three molecular testing platforms in indeterminate thyroid nodules on fine‐needle aspiration

Cited by 21 publications

References 56 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

Communicating risk for thyroid FNA: The pursuit of a better metric

Combining molecular testing and the Bethesda category III:VI ratio for thyroid fine‐needle aspirates: A quality‐assurance metric for evaluating diagnostic performance in a cytopathology laboratory

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