This study evaluated the clinical performance of ThyGeNEXT®, an expanded mutation panel of strong and weak drivers of oncogenic changes, used in combination with ThyraMIR®, a microRNA classifier for the management of indeterminate thyroid nodules. This multi-platform testing (MPTX) of fine needle aspirates was conducted across multiple centers within the US. MPTX test status (positive or negative) and MPTX clinical risk classifications (low, moderate, or high risk) were determined blind to patient outcomes. Testing included 140 patients with AUS/FLUS or FN/SFN nodules, of which 13% had malignancy. MPTX negative test status and MPTX low-risk results conferred a high probability (94%) that patients would remain cancer free. MPTX positive test status (HR 11.2, P<0.001) and MPTX moderate-risk results (HR 8.5, P=0.001) were significant risk factors for malignancy, each conferring a 53% probability of malignancy. MPTX high-risk results elevated risk of malignancy even more so, conferring a 70% probability of malignancy (HR 38.5, P<0.001).
Expansion of the mutation panel to include markers of aggressive disease and the addition of MPTX low, moderate, and high risk classifications improved risk stratification relative to MPTX positive or negative test status.