TEST:

ThyGeNEXT® + ThyraMIR®

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.

This study represents an initial and ongoing effort to investigate the efficacy of molecular testing in the assessment of malignancy risk and prevention of unnecessary surgeries. Our small sample size is due to both molecular testing not being routinely used in our practice and the significant number of cases lost to follow-up. Nevertheless, our findings suggest that molecular "very likely benign" and "low-moderate ROM" assessments are good predictors of a benign surgical result.

Molecular testing of thyroid nodules can help determine the likelihood of malignancy and classify nodules into several tumor phenotypes, predicting their behaviors and potentially allowing for a more tailored treatment. NBNR mutations should be managed with caution.

Although testing positive is associated with malignancy in surgical pathology, the ThyraMIR classifier failed to differentiate between benign and malignant RAS-mutated nodules. Diagnostic lobectomy should be considered for RAS-mutated nodules, regardless of microRNA expression status.

LOH detected in primary PTC significantly predicts ALN status. Analysis of paired primary and metastatic samples from patients with / without ALN status further supports this relationship. The acquisition of LOH at additional loci is common in lymph nodes from patients with ALN status.

A total of 44 nodules were non‐diagnostic were included. Of these, 4 (10. 0%) were read as insufficient allowing the diagnostic assessment of 40 nodules.

More importantly, molecular testing is essential in patients with advanced disease before using any specific mono-kinase inhibitor (e.g. selpercatinib for RET-altered TC), as these drugs are ineffective in the absence of a specific molecular target. This mini-review discusses the utilization of molecular data in the clinical management of patients with thyroid nodules and TC in these different clinical situations.

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*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins.

Large nodules should be sampled via multiple, separate skin entry points when feasible. Judicious use of repeat FNA along with these sampling techniques may help to prevent under-diagnosis in nodules containing multifocal areas of heterogeneous pathology.

Abstracts presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*

"Sub-group analysis, including only patients with surgical pathology, found that PPV tended to be higher in the GSC + XA cohort, at 66.67% (95%CI: 37.28-87.06%), as compared to the ThyGeNEXT + ThyraMIR cohort, at 52.94% (95%CI: 35.25-69.92%). The Afirma genetic testing platform GSC + XA outperformed the other platforms with regards to both PPV and NPV and decreased the rate of surgery in patients with ITNs by 75%, significantly preventing unnecessary surgical intervention."

Our patients' social habits may be associated with the molecular testing results of their indeterminate thyroid nodules but not with their surgical pathology results.

Researchers are yet to arrive at a consensus to figure out a therapeutic regimen and exact dosage of levothyroxine after total thyroidectomy, which could mimic the natural thyroid hormone release, also highlights that unnecessary diagnostic thyroidectomy should be discouraged...With current molecular testing, a significant number of patients undergo diagnostic surgery, but only 30% of those patients are diagnosed with malignant nodules (Heede et al., 2021). An unnecessary ∼70% thyroidectomy rate for benign lesions is not ideal; hence, a rule‐out test directly influences cost‐effectiveness and patient satisfaction.

Following RFA, the majority of nodules (98.6%) were benign by FNA or surgical pathology. RFA does not increase the risk of follicular carcinoma in Bethesda III, IV, and V thyroid nodules.

Molecular testing on cytologically indeterminate thyroid nodules spared more than half of the patients from surgery. This finding emphasizes the value of adding molecular testing, particularly in patients that are poor surgical candidates. Molecular testing did not affect which surgical treatment was performed.

"Interpace Biosciences, Inc...announced new real-world clinical utility data for their ThyGeNEXT® + ThyraMIR®v2 combination test platform to assess the malignancy risk of indeterminate thyroid nodules (ITN). The findings are from an independent study and were shared today in a highlighted poster presentation during the American Thyroid Association (ATA) 2022 Annual Meeting (Poster #119)."

Most nodules had RAS-like mutations and most were benign or low-risk neoplasms (NIFTP). This study supports the role of histologic examination in the distinction of malignancy in RAS-like thyroid neoplasms and underscores the role of molecular testing in risk stratification, patient counseling, and operative management.

"Interpace Biosciences, Inc...announced new clinical validation data for their thyroid cancer test platform which is comprised of a mutation panel (ThyGeNEXT®) and a microRNA (miRNA) risk classifier. The new data demonstrates that the addition of miRNA pairwise expression profiling (ThyraMIR®v2) provides clinically and statistically superior risk stratification of indeterminate thyroid nodules (ITN) beyond that of the algorithmic classification analysis provided by the original ThyraMIR® assay."

As compared to MPTXv1, pairwise miRNA expression analysis used in MPTXv2 significantly improved the diagnostic accuracy of ITN risk stratification and reduced the size of the Moderate-Risk group. Prospective trials are indicated to confirm these findings in a clinical practice setting.

"Interpace Biosciences, Inc...announced today that the National Correct Coding Initiative (NCCI) program issued a response on behalf of the Centers for Medicare & Medicaid Services (CMS) stating that the previously announced billing policy reimbursement for its ThyGeNEXT (O245U) and ThyraMIR (oo18U) tests, disclosed by it in a press release dated January 28, 2022, has been changed retroactive to January 1, 2022. As a result, the Company will continue billing for both tests according to its Laboratory Coverage Determination (LCD) as originally set by Novitas."

"Interpace...announced that it just became aware that the Centers for Medicare & Medicaid Services (CMS) issued a new billing policy whereby CMS will no longer reimburse for the use of the Company’s ThyGeNEXT® and ThyraMIR® tests when billed together by the same provider/supplier for the same beneficiary on the same date of service."

This study demonstrated that the overall RAS mutation-associated ROM in thyroid FNA was intermediate (29%), and isolated HRAS mutations appeared to have a higher ROM (27%) than NRAS and KRAS mutations (15% and 14%, respectively).

Our study demonstrated that the overall ROM in thyroid FNA with associated RAS mutation was intermediate (32%) and NRAS and HRAS mutations appeared to have higher ROM than KRAS mutation. Most malignant cases associated with RAS mutations were cytologically classified as follicular/Hurthle cell neoplasms (Bethesda category IV).