TEST:

ThyGeNEXT® + ThyraMIR®

The ThyroSeq, ThyGeNEXT/ThyraMIR, and Afirma molecular platforms demonstrate similar efficacy in ruling out malignancy in our cohort's cytologically indeterminate thyroid nodules, with sensitivities of 87.5%, 66.7%, and 73.1%, respectively, and negative predictive values of 80.0%, 70.0%, and 66.0%, respectively. Overall performance characteristics of these molecular platforms in our study are inferior to some previously published studies.

Reliable results were obtained from diverse specimen types. The low false-negative rate and positive concordance with histopathology highlights the utility of ThyGeNEXT® + ThyraMIR® in enhancing risk stratification and guiding personalized management of indeterminate thyroid nodules and thyroid cancer.

This study showed that more than half (56%) of the thyroid nodules with indeterminate cytology had benign molecular results by MPTX testing. The MPTX test showed moderate to high NPV and moderate PPV, suggesting that the MPTX test can be useful as an ancillary study to further risk-stratify cytologically indeterminate thyroid nodules. It is critical, however, to know the limitations of this assay, and the molecular results should be considered in correlation with clinical and radiologic findings.

This is the first study to report on the use of combined oncogene and miRNA analysis of FNA cytopathology in a pediatric cohort. Multiplatform molecular testing is a potentially useful adjunct to FNA as a presurgical diagnostic tool in the evaluation of pediatric thyroid nodules.

ThyraMIRv2 platform does not improve indeterminate thyroid nodule malignancy stratification compared to ThyGeNEXT-ThyraMIRv1 multiplatform test version 1. ThyraMIRv2 improves malignant RAS-mutated nodule detection but increases false positives. Future studies encompassing a larger cohort of RAS-mutated with surgical pathology results are warranted to better characterize the performance parameters of this classifier.

miRNA pairwise expression profiling enhances the miRNA algorithmic classifier and mutation status in assessing malignancy risk and allowed for further stratification of both RAS-positive and mutation-negative Bethesda V thyroid nodules.

Both test versions demonstrated robust performance with low false-positive molecular results. Data suggest that incorporation of MPTXv1, and more recently MPTXv2, into clinical practice within our healthcare network resulted in improved accuracy of ITN risk stratification.

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.

While molecular testing has primarily served diagnostic purposes, advancements in understanding genetic alterations now offer therapeutic implications. FDA-approved options target specific genetic alterations, signaling a promising future for tailored treatments.

This integrated approach we feel may enable clinicians to carefully tailor interventions, thereby minimizing the likelihood of unnecessary thyroid surgeries and overall crafting the optimal treatment. By aligning with the evolving landscape of personalized healthcare, this comprehensive strategy ensures a patient-centric approach to thyroid nodule and thyroid cancer management.

Our study found no significant difference in the AUCs of MPTX1 and MPTX2. While NPV showed some improvement between versions, PPV decreased with the increased proportion of false positive cases. Of note, while many of the false positive cases in both test versions correctly picked up neoplasia, the shortcomings in discrimination between malignant and benign neoplasia can trigger unnecessary surgery.

Alone and in combination with ThyraMIR, ThyGeNEXT displayed high SN in our cohort, although SP and NPV were quite low as compared to the Interpace's published performance (SP 98%, NPV 99%). All ThyGeNEXT false positive cases displayed RAS mutations which cannot distinguish between benign and malignant nodules, thus the low SP. Though using the combined test increased NPV to 50%, the testing still missed one malignancy, thus leading to a low NPV.