8763 Independent Real-World Clinical Evaluation of Combined Oncogene-MicroRNA Testing for Thyroid Nodules with Indeterminate Cytology

Abstract Disclosure: A.Y. Joyo: None. N. Silva de Morais: None. D. Tran, MD: None. K.S. Wei: None. T.E. Angell: None. Background: Molecular testing (MT) has become common in the clinical evaluation of thyroid nodules with indeterminate cytology to improve preoperative risk stratification. MT combining oncogene alteration detection (ThyGenX or ThyGeNEXT) and microRNA expression (ThyraMIRv1) is commercially available (Interpace), but its real-world performance has not been extensively studied. We conduct an independent single-center cohort to evaluate the performance of this test platform. Methods: Retrospective analysis of all patients presenting thyroid nodules with Bethesda III or IV cytology tested with ThyGenX or ThyGeNEXT + ThyraMIRv1 at a tertiary academic specialty center from 2016-2022. MT was used based on the treating physician’s decision. Results were categorized as MT negative (MT-) for estimated risk of malignancy (RoM) <10% vs. MT positive (MT+) for RoM ≥10% to create relative consistency with clinical standards for “negative” MT. Additionally, test results were stratified as low, intermediate, and high RoM based on the provided test report. Statistical analysis was performed to determine sensitivity (Se), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV), and test accuracy. Results: There were 131 nodules in 126 patients included (mean [range] patient age, 56 [23-84] years; 93 [74%] women). Of the 131 nodules, 104 (80%) were categorized as Bethesda III and 27 (20%) were Bethesda IV. Median nodule size 2.6 cm (range, 0.6-7.1 cm). There were MT- in 94 (71.8%) cases. Of these, 20 (21.3%) nodules were surgically resected and 7 were malignant (35% of resected nodules, 7.4% of MT- nodules). Surgery was avoided in 74 (78.7%) MT- nodules. There were 37 (28.2%) MT+ nodules, of which 22 (59.5%) were resected and 15 were malignant (68.2% of resected nodules, 40.5% of MT+ nodules). Of nodules with moderate-risk MT, 16/35 underwent surgery and 44% were malignant. Of nodules with high-risk MT, 7/7 patients underwent surgery and 85.7% were malignant. Using a “best case scenario” which assumed all unoperated MT- patients had benign disease and all unoperated MT+ patients had malignant disease, the Se, Sp, PPV, NPV, and accuracy were 80% (95% CI: 66.7 - 93.3%), 90.6% (95% CI: 84.8 - 96.5%), 75.7% (95% CI: 61.9 - 89.5%), 92.6% (95% CI: 87.2 - 97.9%), and 87.8 % (95% CI: 82.2 - 93.4%), respectively. Conclusion: This independent study demonstrates the real-world application of Interpace MT, providing data on test accuracy and clinical utility. In this cohort, 78.7% of patients with an MT- result avoided surgery. Only 45.7% of patients with an MT+ in the moderate risk category underwent surgery, which may indicate an uncertain effect on clinical decision-making. Despite high NPV in the “best case scenario” analysis, the high false negative rate amongst resected MT- nodules raises concern regarding the overall NPV. Presentation: 6/2/2024