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bioRxiv · 10.1101/306126

Inter-institutional variation in predictive value of the ThyroSeq v2 genomic classifier for cytologically indeterminate thyroid nodules

Marcadis, A. R.·Valderrabano, P.·Ho, A. S.·Tepe, J.·Swartzwelder, C. E.·Byrd, S.·Sacks, W. L.·Untch, B. R.·Shaha, A. R.·Xu, B.·Lin, O.·Ghossein, R. A.·Wong, R. J.·Marti, J. L.·Morris, L. G. T.
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Abstract

BackgroundThe ThyroSeq v2 next-generation sequencing assay (ThyroSeq) estimates the probability of malignancy in indeterminate thyroid nodules (ITN). Its diagnostic accuracy in different practice settings and patient populations is not well understood.\n\nMethodsWe analyzed 273 Bethesda III/IV ITN evaluated with ThyroSeq at 4 institutions: 2 comprehensive cancer centers (n=98 and 102), a multicenter healthcare system (n=60), and an academic medical center (n=13). The positive (PPV) and negative predictive values (NPV) of ThyroSeq, and distribution of final pathology were analyzed and compared to values predicted by Bayes Theorem.\n\nResultsAcross 4 institutions, the PPV was 35% (22-43%), and NPV was 93% (88-100%). Predictive values correlated closely with Bayes Theorem estimates (r2=.84), although PPVs were lower than expected. RAS mutations were the most frequent molecular alteration. Among 84 RAS-mutated nodules, malignancy risk was variable (25%, range 10-37%), and distribution of benign diagnoses differed across institutions (adenoma/hyperplasia 12-85%, NIFTP 5-46%).\n\nConclusionsIn a multi-institutional analysis, ThyroSeq PPVs were variable and lower than expected. This is attributable to differences in the prevalence of malignancy, and variability in pathologist interpretations of non-invasive tumors. It is important that clinicians understand ThyroSeq performance in their practice setting when evaluating these results.

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Marcadis, A. R., Valderrabano, P., Ho, A. S., Tepe, J., Swartzwelder, C. E., Byrd, S., Sacks, W. L., Untch, B. R., Shaha, A. R., Xu, B., Lin, O., Ghossein, R. A., Wong, R. J., Marti, J. L., Morris, L. G. T.. 2018-04-22. Inter-institutional variation in predictive value of the ThyroSeq v2 genomic classifier for cytologically indeterminate thyroid nodules. https://doi.org/10.1101/306126

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