Outcome of thyroid gene expression classifier testing in clinical practice

Witt, Robert L.

doi:10.1002/lary.25607

Cited by 24 publications

(27 citation statements)

References 16 publications

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“…4 ). These results are consistent with previously published reports confirming high sensitivity of the GEC [ 19 , 21 – 26 , 34 ]. In this cohort, testing for genetic alterations resulted in 84 % specificity, compared to the GEC, which resulted in 77 % specificity, higher than the 52 % reported in a large, prospective, blinded multicenter study [ 19 ].…”

Section: Resultssupporting

confidence: 94%

The diagnostic application of RNA sequencing in patients with thyroid cancer: an analysis of 851 variants and 133 fusions in 524 genes

et al. 2016

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BackgroundThyroid carcinomas are known to harbor oncogenic driver mutations and advances in sequencing technology now allow the detection of these in fine needle aspiration biopsies (FNA). Recent work by The Cancer Genome Atlas (TCGA) Research Network has expanded the number of genetic alterations detected in papillary thyroid carcinomas (PTC). We sought to investigate the prevalence of these and other genetic alterations in diverse subtypes of thyroid nodules beyond PTC, including a variety of samples with benign histopathology. This is the first clinical evaluation of a large panel of TCGA-reported genomic alterations in thyroid FNAs.ResultsIn FNAs, genetic alterations were detected in 19/44 malignant samples (43 % sensitivity) and in 7/44 histopathology benign samples (84 % specificity). Overall, after adding a cohort of tissue samples, 38/76 (50 %) of histopathology malignant samples were found to harbor a genetic alteration, while 15/75 (20 %) of benign samples were also mutated. The most frequently mutated malignant subtypes were medullary thyroid carcinoma (9/12, 75 %) and PTC (14/30, 47 %). Additionally, follicular adenoma, a benign subtype of thyroid neoplasm, was also found to harbor mutations (12/29, 41 %). Frequently mutated genes in malignant samples included BRAF (20/76, 26 %) and RAS (9/76, 12 %). Of the TSHR variants detected, (6/7, 86 %) were in benign nodules. In a direct comparison of the same FNA also tested by an RNA-based gene expression classifier (GEC), the sensitivity of genetic alterations alone was 42 %, compared to the 91 % sensitivity achieved by the GEC. The specificity based only on genetic alterations was 84 %, compared to 77 % specificity with the GEC.ConclusionsWhile the genomic landscape of all thyroid neoplasm subtypes will inevitably be elucidated, caution should be used in the early adoption of published mutations as the sole predictor of malignancy in thyroid. The largest set of such mutations known to date detects only a portion of thyroid carcinomas in preoperative FNAs in our cohort and thus is not sufficient to rule out cancer. Due to the finding that variants are also found in benign nodules, testing only GEC suspicious nodules may be helpful in avoiding false positives and altering the extent of treatment when selected mutations are found.Electronic supplementary materialThe online version of this article (doi:10.1186/s12859-015-0849-9) contains supplementary material, which is available to authorized users.

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Section: Resultssupporting

confidence: 94%

The diagnostic application of RNA sequencing in patients with thyroid cancer: an analysis of 851 variants and 133 fusions in 524 genes

et al. 2016

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“…al. 14 2014 0.42 (0.32-0.51) 1.00 (0.29-1.00) Han et al 15 2014 0.45 (0.23-0.68) 0.00 (0.00-1.00) Lastra et al 16 2014 0.46 (0.31-0.61) 1.00(0.16-1.00) McIver et al 17 2014 0.16 (0.05-0.33) 0.75 (0.19-0.99) Celik et al 18 2015 0.59 (0.33-0.82) 1.00 (0.16-1.00) Noureldine et al 19 2015 0.42 (0.35-0.50) 0.83 (0.52-0.98) Yang et al 20 2015 0.57 (0.44-0.68) 1.00 (0.48-1.00) Zhu et al 21 2015 0.60 (0.26-0.88) 0.00 (0.00-1.00) Abeykoon et al 22 2016 0.86 (0.57-0.98) 0.00 (0.00-1.00) Chaudhary et al 23 2016 0.38 (0.27-0.50) 1.00 (0.63-1.00) Marti et al 6 2016 0.43 (0.30-0.56) 1.00 (0.59-1.00) Sacks et al 24 2016 0.33 (0.21-0.47) 1.00 (0.40-1.00) Witt et al 25 2016 0.40 (0.16-0.68) 0.00 (0.00-1.00) Wu et al 26 sequencing technology in fine-needle aspiration and tissue samples [17]. This method was superseded by a second, improved version of the assay (ThyroSeq v2) [27].…”

Section: Studymentioning

confidence: 99%

Evaluation of 167 Gene Expression Classifier (GEC) and ThyroSeq v2 Diagnostic Accuracy in the Preoperative Assessment of Indeterminate Thyroid Nodules: Bivariate/HROC Meta-analysis

et al. 2018

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The objective of this meta-analysis was to evaluate the performance of the Gene Expression Classifier (GEC) and ThyroSeq v2 (ThyroSeq) in the preoperative diagnosis of thyroid nodules with indeterminate fine-needle aspiration biopsy results. We searched literature databases from January 2001 to April 2018. The bivariate model analysis was performed to estimate pooled sensitivity, specificity, positive likelihood ratio (LR+), negative likelihood ratio (LR−), positive predictive value (PPV), and negative predictive value (NPV). Pooled data from 1086 nodules with histopathologic confirmation from 16 GEC studies enabled calculation of diagnostic parameters (95% confidence interval): sensitivity 98% (96-99%), specificity 12% (8-20%), PPV 45% (37-53%), and NPV 91% (85-96%). Pooled data from five ThyroSeq studies assessing 459 nodules showed sensitivity of 84% (74-91%), specificity 78% (50-92%), PPV 58% (31-81%), and NPV 93% (89-97%). When both tools were compared, GEC had a significantly higher sensitivity (p = 0.003), while ThyroSeq had a significantly higher specificity (p < 0.001) and accuracy (p = 0.015).

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“…The performance of GEC testing in 210 nodules categorized as atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS; Bethesda category III) or suspicious for follicular neoplasm (SFN; Bethesda category IV), all of which subsequently had definitive surgical pathology diagnoses, demonstrated a test sensitivity of 90%, specificity of 52%, NPV of 94%, and positive predictive value (PPV) of 37% at a cancer prevalence of 24% . Subsequently, 28 real‐world clinical experience studies have cumulatively reported that only 13% of nodules with GEC benign results underwent surgical resection, a marked reduction compared with the historical treatment of patients with cytologically indeterminate thyroid nodules . In 26 of these studies, only 3% of nodules (50 of 1934 nodules) with GEC benign results were found to be malignant .…”

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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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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Outcome of thyroid gene expression classifier testing in clinical practice

Abstract: 4.

Cited by 24 publications

References 16 publications

The diagnostic application of RNA sequencing in patients with thyroid cancer: an analysis of 851 variants and 133 fusions in 524 genes

The diagnostic application of RNA sequencing in patients with thyroid cancer: an analysis of 851 variants and 133 fusions in 524 genes

Evaluation of 167 Gene Expression Classifier (GEC) and ThyroSeq v2 Diagnostic Accuracy in the Preoperative Assessment of Indeterminate Thyroid Nodules: Bivariate/HROC Meta-analysis

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

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