OR32-01 Clinical Performance Of Multiplatform Molecular Diagnostic Testing Of Cytology Indeterminate Thyroid Nodules: A Blinded, Single Institution Observational Study With Surgical Pathology And Surveillance Follow Up

Abstract Disclosure: N.A. Cipriani: None. T. Antic: None. A. Banizs: Employee; Self; Interpace Diagnostics. S.D. Finkelstein: Employee; Self; Employee of Interpace Diagnostics. Background: Genetic analysis of final needle aspiration biopsies (FNAB) can improve the diagnostic accuracy of cytology indeterminate thyroid nodules (ITN). A combination multiplatform molecular algorithmic testing (MPTXv1) approach with mutational analysis (ThyGeNEXT®) complemented by quantitative microRNA (miRNA) expression (ThyraMIR®) can assign nodules to three diagnostic categories: Negative (low malignancy risk), Moderate (intermediate risk), or Positive (high risk). Test performance was assessed in a blinded observational study to evaluate the potential incremental benefit of adding miRNA pairwise expression profiling (MPTXv2) to reduce the Moderate category and improve diagnostic accuracy [RR1] of ITN. Methods: An 11 miRNA marker Profiler was trained to quantify the equilibrium between miRNA pairs supporting growth promotion versus growth suppression using surgical pathology confirmed nodular disease (n=50). Performance without (MPTXv1) and with miRNA pairwise expression profiling (MPTXv2) was assessed using a test cohort of 101 FNAB of ITN (Bethesda Diagnostic Category III/IV) from a single institution. Molecular analysis was performed in blinded fashion with outcome determined based on surgical pathology and surveillance tracking of patients managed for benign disease. Results: MPTXv1 performance (3 categories) without profiler showed 91% sensitivity, 97% specificity, 97% NPV and 85% PPV of 101 patient cohort with 23% cancer prevalence. MPTXv2 performance showed significant [RR2] incremental improvement with 91% sensitivity, 99% specificity, 97% NPV and 95% PPV. Of note, Nodules classified as Moderate malignancy risk decreased from 25 to 6 patients (a 76% reduction). Conclusion: Diagnostic test performance limitations inherent in isolated mutational or isolated RNA classifier analysis to both rule-in and rule-out of thyroid cancer can be improved by a combination platform [RR5] approach (MPTX) which can delivers high sensitivity and specificity. Furthermore, blinded observational analysis of deeper analysis by incorporating miRNA pairwise expression profiling (MPTXv2) further improves performance by increasing the proportion of patients that will receive a highly accurate prediction of ITN status, reducing false positives and negatives Presentation: Sunday, June 18, 2023