Role of Gene Expression Classification in Assessing Thyroid Nodules
That is correct. However, although nodules are more common with age, our medical technology has advanced, and medical imaging is much more common. Many thyroid nodules are found incidentally on ultrasound, such as used in carotid screening. When a nodule is detected, the physician identifies characteristics of the nodule that influences his or her treatment decisions.
EW: Can the biopsy outcome by fine needle aspiration (FNA) for cytopathologic evaluation define the signatures of the nodule, such as ruling out cancer?
Not always. Some nodules are indeterminate. It is amazing the number of people who receive diagnostically ambiguous results, based on cytopathology, and end up undergoing a partial or total thyroidectomy. The fact is 70% to 80% of these patients who undergo surgery are found to have benign nodules and thus could have avoided surgery if there was a better test, which is available today—the Afirma® Gene Expression Classifier (GEC) (Veracyte, Inc.). This molecular test is part of a comprehensive solution to manage patients throughout the thyroid nodule diagnostic process. The solution also includes initial thyroid-specialized cytopathology, as well as molecular testing to inform preoperative surgical decision-making for those patients who require surgery.
It is expected that more than half a million biopsies will be performed each year in the United States (US). Approximately 15% to 30% of these biopsies may end up cytologically indeterminate. Using the GEC, about half are found to be genomically benign, suggesting that coupled with clinical judgment, these patients can typically be followed and observed. The GEC helps spare patients an unnecessary operation and surgical risks, and saves the health care system dollars for unnecessary procedures.
EW: Does the GEC require any change in how the physician performs FNA?
The FNA is performed as it is routinely done. The thyroid nodule material is collected for cytopathology. During the same procedure, the physician collects two additional passes for the GEC molecular test, which are placed in a separate tube provided by Veracyte. The molecular test should be performed when the cytology is indeterminate.
EW: Who requests the GEC—the physician, the pathologist?
The physician sends in the FNA material for both cytopathology and, if necessary, molecular testing. If the pathologist deems the results indeterminate, then the materials are reflexed to the GEC. However, the ordering physician remains in control and can decide on a case-by-case basis; but it is routine to reflex in those situations to provide patients a result as fast as possible.
EW: Is this testing only available at academic centers where a pathologist routinely examines thyroid samples?
Historically, the average physician practicing in the US has been utilizing pathologists who often don’t read very many thyroid samples. In other words, the bulk of their clinical experience is not thyroid biopsies and so a high-volume, highly experienced pathologist has not been in charge of their samples.
Veracyte has partnered with a particular laboratory to read cytopathology for those community-based physicians. We believe this has raised the quality of patient care dramatically, because high-volume experts are much more able to make benign and malignant calls, and help keep the rate of indeterminates low. When these experts can’t make a definitive call, the results of the Afirma molecular test can help spare many of these patients an unnecessary operation.
As of the end of June 2014, nearly 115,000 FNA samples have been brought in for the Afirma solution, with over 20,000 GEC tests from academic and community physicians specifically used to resolve diagnostic ambiguity. We estimate that Afirma has saved over 10,000 patients from unnecessarily having their thyroids removed.
EW: What is the GEC’s role in detecting medullary or papillary carcinomas?
The GEC is used to help identify patients with benign nodules, among those deemed indeterminate by cytopathology, so these patients can potentially avoid unnecessary surgery. Additionally, we recently added our Afirma Malignancy Classifiers—comprised of tests for medullary thyroid cancer, or MTC, and to assess BRAF gene mutational status—to help guide surgical strategy for those patients who need surgery.
MTC is often challenging to distinguish by cytopathology, but this ability is important because the type of surgery for a patient with suspected MTC is typically different from those with other suspected types of thyroid cancer. In the past, many medullary thyroid cancer cases underwent incomplete initial operations, which then often required a second surgery.
Many physicians also opt to perform more extensive surgeries for patients with a suspected BRAF gene mutation. Both of the malignancy classifiers help physicians determine the extent of initial surgery, if surgery is required.
In summary, our goal is to avoid surgery when appropriate with the GEC. When surgery is necessary, the malignancy classifiers help physicians perform the optimal surgery the first time.