TEST:

Afirma® Genomic Sequencing Classifier

The detection of BRAF fusions and their many partners was enabled by the Afirma XA exome-enriched RNASeq panel. Although BRAF fusions occurred in only 0.2% of thyroid nodules, they were GSC-Suspicious and lacked typical BRAF/RAS mutations. Interestingly, expression signatures associated with malignancy varied by fusion partner.

In older adolescents with ITN, the A firma GSC showed excellent performance when de fining a true negative result by histology or clinical follow-up. Our findings indicate that an A firma GSC-B result appears reassuring and may allow for a more conservative management strategy in younger patients with ITN.

Longer follow up will be necessary to confirm the persistent efficacy and safety in the study cohort. Additionally, prospective trials will be important to advise guidelines regarding minimally invasive treatment techniques for ITN with benign molecular test results.

P=N/A, N=50, Recruiting, Columbia University | Trial completion date: Aug 2024 --> Aug 2026 | Trial primary completion date: Aug 2023 --> Aug 2025

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.

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.

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.

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.

For ATA low-risk disease she was subsequently monitored with thyroglobulin levels and treated with levothyroxine to goal TSH<2 without evidence of recurrence.Molecular testing and FNA pathology are adjuncts to the clinical assessment for thyroid cancer rather than substitutes...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.

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.

The analytical robustness and reproducibility of the Afirma TERT test support its routine clinical use among thyroid nodules with indeterminate cytology that are Afirma GSC suspicious or among Bethesda V/VI nodules.

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.

GSC is a key tool for managing patients with indeterminate cytology, including the higher-risk Bethesda IV category. GSC benign thyroid nodules can be observed similarly to thyroid nodules with benign cytology.

BCR and diagnostic parameters of GSC testing may vary in AUS-N vs AUS-O subcategory in both single AUS and repeat AUS groups. GSC demonstrated comparable performance in thyroid nodules with a repeat versus single AUS diagnosis.

Immunohistochemistry: - Positive for p40, cytokeratin AE1:AE3, CD5 (rare cells), synaptophysin (rare cells) - Negative for NUT, PAX8, TTF-1, chromogranin, thyroglobulin, calcitonin - Ki67 proliferation index: 50% Figure 1 Caption: Click the link below to view the virtual slide. Figure 1 Virtual Slide: https://conferences.aiforia.com/Public/USCAP/5HyBcnwzXnmll15SJfRYhCjUGyovFRoosTAMilaU4Oo0 Figure 2: Click to view full size Figure 2 Caption: Cytokeratin AE1/AE3 Figure 3: Click to view full size Figure 3 Caption: P40 Figure 4: Click to view full size Figure 4 Caption: CD5 Figure 5: Click to view full size Figure 5 Caption: Synaptophysin

P=N/A, N=328, Active, not recruiting, Jonsson Comprehensive Cancer Center | Recruiting --> Active, not recruiting | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2023 --> Dec 2024

Afirma XA improved risk stratification of thyroid disease with a high risk of malignancy in Afirma GSC suspicious nodules. A negative Afirma XA result, however, should not be used as a rule-out test.

Binary reporting of AUS subclasses based on nuclear atypia distinguishes cases with a higher risk of NIFTP/cancer. There is a low but non-negligible prevalence of NIFTP/cancer in cases without nuclear atypia.

"Veracyte...announced that six abstracts highlighting new data from studies evaluating the company’s Decipher Prostate Genomic Classifier and related capabilities will be presented, three as oral presentations, at the American Society for Radiation Oncology (ASTRO) Annual Meeting 2023 taking place October 1-4 in San Diego."

"Veracyte...announced that three posters showcasing new data from the company’s Afirma Genomic Sequencing Classifier (GSC) will be presented at the 2023 American Thyroid Association (ATA) Annual Meeting being held in Washington, DC from September 27 to October 1. Together, these abstracts offer novel insights into the molecular underpinnings of thyroid nodules and tumors based on whole-transcriptome RNA sequencing data from thyroid nodules analyzed with the Afirma GSC."

We present the case of a suspicious thyroid nodule that completely resolved while being treated with Pembrolizumab and Lenvatinib immunotherapy for metastatic uterine cancer. The patient is a female in her mid‐50s with stage IVB uterine serous carcinoma who underwent oncologic resection then carboplatin and paclitaxel therapy followed by bevacizumab, but had progression of disease...She was intermittently on levothyroxine during this time for hypothyroidism...Pembrolizumab is known to cause adverse effects on the thyroid, including hypothyroidism. It is unclear which, if either, of these immunotherapies were responsible for complete resolution of the suspicious nodule or could have any treatment potential in the future for malignant thyroid nodules.

mRNA expression based Afirma GSC evaluation allows for pre‐operative immunophenotyping of thyroid cancers, as an alternative to traditional immunohistochemistry techniques on surgical specimens. Future prospective studies are warranted to evaluate whether the GSC assay can predict thyroid cancer response to immune checkpoint inhibitor therapy.

Isthmic FVPTC have higher scores of BRAF‐like molecular signatures, ERK, and FMT signaling relative to lobar cancers. Classic PTC only showed higher levels of FMT in the isthmus relative to the lobar locations. More data is needed to know if a change in surgical therapy is warranted in isthmic thyroid cancers relative to lobar cancers and if this molecular data should influence isthmic thyroid cancer management and monitoring.

There were 30,259 cytologically indeterminant (cyt_I) nodules classified as GSC‐Benign (GSC‐B), 15,815 cyt_I nodules classified as GSC‐Suspicious (GSC‐S), and 1,621 nodules were cytologically Bethesda V or VI. Mean expression of the NIS gene was lower in GSC‐S and Bethesda V/VI nodules as compared to GSC‐B (Wilcoxon rank‐sum p‐value <2e‐16 for both). Relative to GSC‐B, GSC‐S and Bethesda BV/VI had a fold change (FC) of 0.

No abstract available

GSC demonstrated comparable performance in thyroid nodules with a repeat AUS diagnosis versus nodules with an initial AUS diagnosis.

"Veracyte...announced that new data presented at ENDO 2023, the annual meeting of The Endocrine Society, suggest the company’s Afirma molecular testing and whole-transcriptome capabilities can provide novel insights that may advance the scientific understanding of thyroid nodule biology. In addition, findings from an analytical validity study presented at the meeting show that the Afirma TERT promoter mutation test performs with high analytical sensitivity and specificity."

The Afirma TERT test also demonstrated a 100% confirmation rate when compared with an external NGS-based reference assay executed in a non-Veracyte laboratory. The analytical robustness and reproducibility of the Afirma TERT test support its routine clinical use among thyroid nodules with indeterminate cytology that are Afirma GSC suspicious or Bethesda V/VI nodules.

Our study provides evidence of the real-world performance of the Afirma GSC and supports its use as a non-invasive tool for the management of indeterminate thyroid nodules. Better oSP and oPPV are suggestive of higher yield of cancers for resected nodules based on suspicious GSC.

"Veracyte...announced that three abstracts highlighting new data on the company’s Afirma test and capabilities will be presented at ENDO 2023, the annual meeting of The Endocrine Society, which is taking place June 15-18 in Chicago, Ill. Additionally, Veracyte’s medical director of Endocrinology, Joshua Klopper, M.D., will participate in a symposium panel discussion on the advantages of various molecular testing approaches to help personalize and improve care for people with potentially cancerous thyroid nodules."

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."

The majority of Bethesda III/IV thyroid nodules with negative or benign molecular test results are stable over 3 years of follow-up. These findings support the high sensitivity of current molecular tests and their role in ruling out malignancy in indeterminate thyroid nodules.

"Veracyte...announced that data published in Frontiers in Endocrinology provide new insights into the frequency and risk of malignancy (ROM) associated with thyroid stimulating hormone receptor (TSHR) mutations in indeterminate thyroid nodules. The findings, which were derived from analyses of Veracyte’s comprehensive thyroid nodule database of whole transcriptome sequencing, suggest that the use of Afirma testing could help inform diagnoses and personalized treatment decisions for patients with thyroid nodules."

TSHR variants are rare in ITN, and most are categorized as benign under Afirma GSC testing which carries a < 4% risk of malignancy. For GSC-S ITN with TSHR mutations, the risk of malignancy is ≥= 15%, which is clinically meaningful and may alter treatment or monitoring recommendations for patients.

Afirma XA detected abnormalities in approximately one-third of Afirma GSC suspicious nodules, of which RAS mutations were the most common finding (68%). Two-thirds of cases labeled suspicious by Afirma GSC did not reveal gene mutations or fusions by Afirma XA testing, suggesting other unknown genetic alterations requiring further investigation.

Compared to nodules with a single AUS diagnosis, nodules with a repeat AUS diagnosis demonstrate similar BCR and malignancy rate for suspicious GSC results. Diagnostic parameters of GSC did not differ between the two cohorts of thyroid nodules.

XA improved risk stratification and identification of malignant thyroid disease with a very high ROM in GSC “suspicious” nodules. Although a negative XA result was associated with lower RoM in our cohort, a negative XA result should not be used as a “rule-out” test.

Binary reporting of AUS subclass based on nuclear atypia distinguishes cases with higher risk of NIFTP/cancer. NIFTP/cancer prevalence of 20% based on molecular/histologic endpoints is within range of disease prevalence used for clinical validation of the Afirma test. Cases classified as AUS-Other have low but non-negligible prevalence of NIFTP/cancer.

"Veracyte...announced that findings demonstrating the strong real-world performance of the Afirma Genomic Sequencing Classifier (GSC) were published in The Journal of Clinical Endocrinology & Metabolism (JCEM). The data, from a meta-analysis of 13 independent studies, show that the Afirma GSC can accurately rule out thyroid cancer in patients with indeterminate thyroid nodules (ITNs) and that, when the test identifies a nodule as suspicious, the patient’s risk of malignancy is consistent with, and higher than, that reported in the test’s original clinical validation (CV) study."

RW data for the Afirma GSC demonstrates significantly better oSP and oPPV performance compared to the VS, indicating an increased yield of cancers for resected GSC suspicious nodules. The higher BCR likely increases the overall rate of clinical observation in lieu of surgery.

Meta-analyses reveal high diagnostic accuracy of molecular tests for thyroid nodule assessment of malignancy risk; however, these studies are subject to several limitations. Limitations and their potential clinical impacts must be addressed and, when feasible, adjusted for using valid statistical methodologies.