Dr. Alexander is Chief, Thyroid Section of the Division of Endocrinology, Diabetes and Hypertension at Brigham and Women’s Hospital. He was lead author on the clinical validation study for the original Afirma test whose results were published in The New England Journal of Medicine. His team has used Afirma since 2011 and began using the Afirma Genomic Sequencing Classifier (GSC) shortly after it became available in 2017.
Q: First, can you provide some context on the role of molecular testing – and, specifically, the Afirma GSC – in thyroid cancer diagnosis?
Dr. Alexander: Cytopathology has limitations and often produces indeterminate results that can lead to unnecessary surgeries because many of these nodules are benign. The original Afirma test was developed to help reduce unnecessary surgeries by identifying patients with benign nodules among those that were indeterminate by cytopathology – so it was designed to maximize the NPV. Molecular testing has continued to evolve and now the Afirma GSC is designed to maintain that high NPV, while further increasing the number of benign nodules that it identifies.
Q: What was this new study designed to do?
Dr. Alexander: We wanted to see if the next-generation test did in fact identify more benign nodules than the original test and also if the Afirma GSC’s metrics were any different from the validation study findings [published recently] in JAMA Surgery.
Q: What did you find?
Dr. Alexander: The results were very encouraging, as we had hoped. Our findings showed that the Afirma GSC increased the benign call rate from under 50 percent to nearly two-thirds of the indeterminate nodules tested, compared to the original test. This rate is similar to what was found in the recent clinical validation study. In particular, we found that the next-generation Afirma test showed a significant improvement in its ability to identify benign Hürthle cases. This is important because distinguishing between benign and cancerous Hürthle nodules has traditionally been challenging with both cytopathology and molecular testing.
Q: Any final thoughts on the significance of your findings?
Dr. Alexander: Everyone wants the perfect test in thyroid cancer diagnosis. And while no test is absolutely perfect, I think our findings show that the Afirma GSC marks a big step towards ultimately achieving that goal.