Veracyte data advance understanding of the role of gene alterations in thyroid cancer diagnosis
May 31, 2016 – SOUTH SAN FRANCISCO. Veracyte, Inc., a molecular diagnostics company pioneering the field of molecular cytology, today announced findings from two studies demonstrating the challenge of using large gene-mutation panels to help physicians determine next steps for patients whose thyroid nodules are not clearly benign or malignant following routine cytopathology evaluation. Company researchers also unveiled a new study designed to identify RNA-based gene alteration and other data that may be useful in guiding physician decision-making for thyroid nodule patients. The studies are being presented at the American Association of Clinical Endocrinologists (AACE) 25th Annual Scientific & Clinical Congress, taking place May 25-29, 2016, in Orlando, Fla.
More than 525,000 Americans are evaluated for potentially cancerous thyroid nodules each year. While most nodules are benign, up to 30 percent are deemed inconclusive based on microscope-based review. Traditionally, many of these patients have been directed to thyroid surgery for more definitive results, only for most (70-80 percent) to learn after the invasive, costly procedure that their nodules were benign.
“As gene alterations and fusions are linked increasingly to thyroid cancer in the literature, there is growing interest among clinicians regarding how this genomic information can be used to enhance thyroid cancer diagnosis,” said Giulia C. Kennedy, Ph.D., chief scientific officer of Veracyte. “Findings from two studies presented at the AACE meeting, however, suggest that gene variant and fusion panels on their own have limited ability to help rule in or rule out cancer in patients with indeterminate thyroid nodules. These results are consistent with previous findings and underscore the need to clarify the role that gene alterations may potentially play in guiding the care of patients being evaluated for potential thyroid cancer.”
In the first study, researchers conducted a meta-review of the relevant body of literature to determine the value of RAS mutations – which have been linked to thyroid cancer – in identifying malignancy in indeterminate thyroid nodules. In a review of 17 studies involving 2,035 cytologically indeterminate nodules, RAS mutations had a sensitivity of 30 percent, suggesting that 70 percent of cancers would be missed if RAS mutations were used to rule out cancer. In a review of 19 studies involving 2,099 thyroid nodules, RAS mutations were found in 13 percent of benign nodules, suggesting that their use to identify malignancy could lead to unnecessary treatment of many patients who do not have cancer.
In a second study, Veracyte scientists used DNA sequencing to evaluate the ability of three large gene-mutation panels to rule in or rule out cancer in 82 thyroid fine needle aspiration (FNA) samples and 38 thyroid tissue samples. The researchers found that a panel targeting 229 alterations in 14 genes had a sensitivity of only 55 percent for detecting cancer (i.e., it missed cancer 45 percent of the time). A custom panel of 854 alterations in 357 genes derived from the literature and The Cancer Genome Atlas had a sensitivity of just 67 percent. Using a 358-gene panel (The Jackson Laboratory Cancer Treatment Profile), the researchers found that the sensitivity increased to 90 percent, but was accompanied by a low (11 percent) specificity (i.e., it elicited many false positives).
Veracyte and external researchers also presented the design of a new study to advance the understanding of genomic alterations and transcriptional expression in thyroid nodule patients with indeterminate cytopathology. Through the Evaluation of Thyroid FNA Genomic Signatures (ENHANCE) trial, Veracyte has established a comprehensively annotated bio-repository of FNA samples that are tagged with genomic and histopathology data, as well as clinical and radiological information when possible, to determine which features signal cancer – and in what relation to each other – and which do not. As of December 2015, 39 academic and community study sites have opened across the United States and 650 patients have enrolled in the study.
“We look forward to the ENHANCE study helping us better understand the role of genomic alterations and other factors in thyroid cancer and to determine how this information could potentially be used with our Afirma® Gene Expression Classifier (GEC) to further guide care for thyroid nodule patients,” said Dr. Kennedy.