Genomic Diagnostics company Veracyte says new data demonstrates the clinical and analytical validity of its Afirma Xpression Atlas (XA) genomic test, which was developed to help guide surgery and treatment decisions for patients with likely or confirmed thyroid cancer. This data is reported online in the journal Frontiers in Endocrinology.
Veracyte develops genomic classifiers using RNA whole-transcriptome sequencing and machine learning. Affirma XA detects expressed DNA variants and RNA fusion partners in over 500 genes associated with thyroid cancer.
“Our findings suggest that the Afirma XA is sensitive and accurate in identifying gene alterations that are associated with thyroid cancer and confirm that the test can do this using one patient sample for all molecular testing,” said Trevor E. Angell, assistant professor of clinical medicine at the Keck School of Medicine of USC and lead author of the new paper. “The extensive genomic-alteration information provided by the Afirma test can help physicians tailor initial treatment for patients with likely or confirmed cancer and also provides information about the potential benefits of targeted therapies for those cancers that don’t respond to standard treatment.”
The test is performed on fine needle aspiration (FNA) samples of thyroid nodules deemed suspicious for cancer by Veracyte’s Afirma Genomic Sequencing Classifier (GSC) or already diagnosed as cancer based on cytopathology. Afirma XA can be performed on the same FNA sample as the Afirma GSC, which allows patients to avoid an additional FNA procedure.
To evaluate the Afirma XA’s clinical validity, researchers compared the test’s ability to identify genomic variants in an FNA sample’s transcriptome to currently accepted methods of targeted DNA and RNA sequencing. Using 943 blinded FNA samples, they found the Afirma XA had high positive predictive agreement (PPA) with targeted DNA sequencing (88 percent) and targeted RNA sequencing (89 percent). Similarly, using 695 blinded FNA samples to look for RNA fusions, the Afirma XA had an 82 percent PPA with targeted RNA sequencing. Conversely, 95 percent or more of variants and fusions identified by Veracyte’s RNA whole-transcriptome sequencing test were also identified by the reference method.
The researchers also investigated Afirma XA’s reproducibility across laboratories and reagent lots. Using 69 variant-positive FNA samples, they found the test showed high accuracy between two different labs with different personnel for detecting variants (90 percent) and fusions (94 percent).
“The use of pre-operative molecular testing with minimally invasive FNA samples is expanding beyond cytologically indeterminate thyroid nodules to include those nodules with clear malignancy. Our findings demonstrate that physicians can be confident in the Afirma XA’s results at the time of diagnosis, which help guide surgery and treatment decisions,” said Richard T. Kloos, M.D., medical director of endocrinology for Veracyte and an author of the new study.
Every year approximately 525,000 US patients undergo FNA biopsies to evaluate thyroid nodules for cancer. Up to 30 percent of these patients receive “indeterminate” results – their nodules are not clearly benign or malignant– and most of those people are directed to diagnostic surgery. But 70 percent to 80 percent of the time “indeterminate” nodules prove to be benign. Since multiple precision medicine therapies are now available, or in development, to treat this cancer based on its genomic profile, the Afirma XA could prove to be a pivotal new tool for management of this disease.
Since its founding in 2008, Veracyte has commercialized seven genomic tests aimed to transform the diagnosis of thyroid cancer, lung cancer and idiopathic pulmonary fibrosis. Its current product lines are all diagnostics that use genomic classifiers: Afirma for thyroid cancer, Percepta for lung cancer, and Envisia for idiopathic pulmonary fibrosis.