Q: What exactly is the Afirma Xpression Atlas?
Dr. Sadow: It’s a gene-alteration test, based on RNA sequencing, that’s intended for thyroid nodule patients who are going to surgery. It provides additional genomic information that may be considered to risk-stratify patients whose nodules are Bethesda III or IV and called suspicious by the Afirma GSC or that are Bethesda V or VI, based on cytopathology. The Xpression Atlas’s gene variants and fusions were derived from the thyroid literature and from The Cancer Genome Atlas (TCGA). TCGA data were published in Cell in 2014.
Q: What were you trying to determine in this study?
Dr. Sadow: We wanted to see how reliable the results of the Xpression Atlas were compared to a reference method. In other words, when it identifies a specific mutation in actively transcribed genes, is a mutation really present?
Q: How did you go about this and what did you find?
Dr. Sadow: Scientists at Veracyte used custom-developed DNA- and RNA-based panels as the reference standard and then conducted molecular testing on over 500 FNA samples to compare the tests in a blinded manner. Agreement between the Xpression Atlas and the reference methods was high. Specifically, when the Xpression Atlas identified variants and fusions, the reference methods were over 98.5 percent concordant.
Q: What’s the significance of the Xpression Atlas in managing patients with thyroid nodules?
When patients are destined for surgery to exclude thyroid cancer, the Xpression Atlas provides additional genomic information that the treating physicians may use in their discussions with patients to agree on an optimal surgical approach and management plan. The Xpression Atlas will provide more genomic information to treating physicians than has been previously available, so we are going to learn a lot with this test. This genomic information may be considered, along with an individual patient’s specific circumstances, to inform the decision process. Modest published data has associated some variants or fusion gene products with thyroid cancer, lymph node metastases, or presentation with higher stage disease. This information is certainly something to consider when in discussions about a primary treatment plan. It is important to note, however, that randomized treatment trials based on genomic features have not been performed to know that patient outcomes are improved based on these strategies. The Xpression Atlas would facilitate such studies to be conducted.
Importantly, the Xpression Atlas is not intended to exclude cancer. Veracyte showed at ENDO 2018 that the reference panel was negative in about one half of the thyroid cancers found in Bethesda III and IV nodules and one fifth of the thyroid cancers found in Bethesda V and VI nodules. So, the key to the Xpression Atlas is that it’s used on patients who are already going to surgery with the intention that the Xpression Atlas adds incremental data.
Q: What about future benefits of the data that the Xpression Atlas provides?
Dr. Sadow: As more becomes understood about gene alterations and their impact on cancer development, prognosis, and tumor pathway dependence, this information will become increasingly useful. For example, the test could one day help inform treatment if the patient has a cancer recurrence or metastasis.
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