Afirma Thyroid Analysis May Help Patients Avoid Surgery

Nodules No Longer Classifed as Inconclusive or Indeterminate

Afirma Thyroid Analysis
The Afirma Thyroid Analysis may help patients with an indeterminate nodule avoid unnecessary thyroid surgery. istockphoto

Thyroid cancer is the fastest-growing cancer in the United States. There were an estimated 44,670 new cases in 2010, according to the American Cancer Society. Along with the increased awareness of thyroid cancer comes increased scrutiny of thyroid nodules. Thanks to more vigilant monitoring, ultrasounds, and x-rays, more thyroid nodules are being detected and evaluated.

When a thyroid nodule is considered suspicious -- meaning that it has characteristics that may suggest thyroid cancer -- the key evaluation is a fine needle aspiration (FNA) biopsy.

The FNA biopsy helps determine whether the nodule is malignant (thyroid cancer) or benign.

One of the most frustrating challenges facing endocrinologists and thyroid patients is when an FNA on a suspicious nodule is found to be "inconclusive" or "indeterminate." In this case, the pathology assessment cannot rule out cancer, and the recommended follow-up is thyroidectomy -- a surgery to remove the thyroid. The thyroid gland is then thoroughly evaluated by a pathologist to conclusively diagnose or rule out thyroid cancer.

When thyroid cancer is found, the thyroidectomy is considered a necessary and appropriate step in treatment.

But when no thyroid cancer is discovered, the patient has needlessly lost a vital organ, and in the process, become hypothyroid for life. The health impact of an unnecessary thyroidectomy can be life-changing -- those patients become hypothyroid and face a lifetime of tests, treatment and monitoring, as well as the symptoms and conditions associated with hypothyroidism.

In addition to the health impact, these needless thyroid surgeries are costly, and a drain on the healthcare system. The cost of thyroid surgery typically runs $15,000 to $20,000, and when the gland is needlessly removed, there are additional lifelong costs for blood tests, hypothyroidism medications and physician monitoring.

How Many People are Affected?

Let's look at the extent of the problem. First, it's estimated that approximately 450,000 suspicious thyroid nodules undergo FNA annually in the United States. Up to 30% of the nodules assessed by FNA are indeterminate/inconclusive, meaning that thyroidectomy is recommended to as many as 135,000 patients due to an inconclusive FNA.

The crucial issue is that only 20 to 30 percent of inconclusive nodules turn out to be malignant. That means that as many as 100,000 patients in the US each year could end up undergoing a needless thyroidectomy, due to inconclusive nodules that turn out to be benign.

A new test, called the Afirma Thyroid FNA Analysis, can help avoid the negative health effects and costs of these needless thyroidectomies. The test, developed by a company called Veracyte, can help patients and physicians avoid inconclusive results on thyroid nodules through a two-step process. The first step is cytopathology -- pathology assessment at the cellular level -- by Thyroid Cytopathology Partners (TCP), an independent laboratory partner of Veracyte.

Indeterminate samples go through step two, a proprietary Gene Expression Classifier, which then classifies indeterminate nodules as either benign or suspicious.

According to Bonnie Anderson, Veracyte cofounder and Chief Executive Officer, "The goal of the Afirma Thyroid FNA Analysis is to give doctors better information that can help patients with thyroid nodules avoid inconclusive FNA results –- and the potential diagnostic odyssey and unnecessary surgery that can follow such results. We believe this will not only improve patient care, but will also provide cost savings to the healthcare system."

The Afirma Thyroid FNA Analysis Process

Currently, the Afirma process can be used to evaluate adult patients (21 or older) with nodules greater than or equal to 1 cm in size.

Before an FNA is scheduled or performed, a patient who wants to use the Afirma Thyroid FNA Analysis Process needs to identify a treating physician who is already familiar with the test's collection process, and has the proper supplies on hand that are needed to collect and ship the sample. The test is not yet widely available throughout the country.

The treating physician performs a single FNA, which usually involves 4 to 5 samples, also known as "passes." The FNA sample is then split, with two passes collected for initial cytopathology and two passes collected in the event the first assessment is inconclusive. The physicians use standard thyroid FNA technique -- no special training is necessary -- but do collect the samples using sample collection and transport supplies provided by Veracyte.

The treating physician sends the patient samples overnight to Thyroid Cytopathology Partners, and the samples are then evaluated. They make a cytopathology diagnosis, and if the nodule is clearly benign or malignant, the Afirma Thyroid FNA Analysis is complete. A patient report is prepared and sent to the treating physician, usually within five days.

If the cytopathology is indeterminate, then the samples go on to a second step -- the Gene Expression Classifier. This is a genomic test that measures gene expression patterns of the sample to make a diagnosis of either "benign" or "suspicious for malignancy." If the initial cytopathology results are indeterminate, and the Afirma Gene Expression Classifier is used, the report usually is sent within 14 days.

Richard Lanman, MD, Veracyte's Chief Medical Officer, explains what it means to measure gene expression patterns:

"This refers to the ability to determine if particular genes in a cell are expressed, or 'turned on,' and how they are expressed in relation to each other as an indicator of the nodule's behavior -– for example, whether the nodule is benign or potentially cancerous. To develop the Afirma Gene Expression Classifier, Veracyte evaluated hundreds of thyroid samples to identify 142 different genes that best distinguish benignity from malignancy. The test is then based upon powerful algorithms and sophisticated statistical approaches that determine if and to what degree these genes are activated in a given thyroid FNA sample."

If after either step, the analysis shows the nodule to be benign, then periodic followup and monitoring of the nodule -- as is recommended for any benign nodules -- is typically recommended.

Overall, a series of trials evaluating the Afirma Thyroid FNA Analysis have shown that in more than 95% of the cases, when the test indicated that cancer was not present, there was in fact no cancer present.

The test underwent two independent validation studies in 2010, and many of the investigators involved in the clinical validation study are currently offering the test to patients.

A larger, prospective, multi-center study is underway to further evaluate the test data, and those results are expected to be published in late 2011 or early 2012.

Data from researchers at Johns Hopkins University School of Medicine also suggest that routine use of the Afirma process nationally would reduce the number of surgeries on patients with benign thyroid nodules by 74 percent -- or 50,000 each year -- and would generate in excess of $600 million in direct medical savings over a five-year period.

Paul Ladenson, MD is professor of endocrinology and metabolism and director of the Division of Endocrinology and Metabolism at the Johns Hopkins Medical Institutions, and was one of the researchers involved in the cost analysis of the Afirma Thyroid FNA Analysis. According to Dr. Ladenson:

The clinical and economic impacts of implementing this new technology are, in fact, similar in magnitude to those that accompanied the introduction almost 40 years ago of FNA cytology to differentiate between benign and malignant thyroid nodules. We found that, even when we assessed a wide range of possible scenarios in our economic model, 93% of our projections using the gene expression test actually reduced costs while improving health outcomes. This is a rare finding for implementation of a novel management strategy.
According to Richard Lanman, MD, Veracyte's Chief Medical Officer:
"The Afirma Gene Expression Classifier is intended to help rule out cancer in those indeterminate FNA samples that are truly benign. Results are classified as either benign or suspicious for malignancy. Studies to date have shown the Afirma Gene Expression Classifier's false-negative rate to be about 5%, which is in line with the false-negative rate of benign cytopathology. Today, most patients with an indeterminate cytopathology result go to surgery, but only 30% are malignant. The Afirma Gene Expression Classifier does not make a malignant call. Rather, it is optimized to identify benign FNA samples among those classified as indeterminate by cytopathology. In doing so, data show the test can reduce by half the two-thirds rate of false positives associated with current practice."
In addition to reducing the number of surgeries on patients who have benign nodules, research reported on in the Journal of Clinical Endocrinology and Metabolism also found that routine use of the Afirma process could increase by more than 50% the likelihood that patients who have surgery actually do have thyroid cancer.

Bryan Haugen, MD, who was leading clinical trials of the Afirma Thyroid FNA Analysis, told the 14th International Thyroid Congress in September, 2010: "A test with this high of a negative predictive value will help doctors rule out malignancy and confidently monitor many patients with ambiguous thyroid nodules, enabling these patients to avoid unnecessary surgery."

 

What You Need to Know As a Patient

Because the Afirma Thyroid FNA Analysis is new, many endocrinologists and physicians are not offering it at present. So if you are going to undergo an FNA biopsy and want the Afirma Thyroid FNA Analysis used, you need to have the FNA performed by a physician who is already using the test. Patients can call Veracyte for information on physicians who offer the service.

You can also speak with your physician about offering the Afirma process. According to Veracyte, physicians and their staff can be trained in one day to adopt the Afirma FNA Thyroid Analysis process.

If you have already had an FNA biopsy that found an indeterminate nodule, and your physician is recommending thyroidectomy, you may be interested in having another FNA done with a physician who uses the Afirma Thyroid FNA Analysis process. Having a conclusive result could potentially prevent an unnecessary surgery.

The Afirma Thyroid FNA Analysis test process is priced at around $3,500.

Veracyte is currently accepting all insurance to pay for the test, and they will manage the claims process for patients. To date, several insurance companies are already reimbursing for the test. Veracyte has also set up a program called "Afirma Access," which helps patients manage out-of-pocket expense in cases where the insurance carrier may not agree to coverage.

For more information, see the Veracyte website for Afirma at http://www.veracyte.com/afirma.

Sources:

July 25, 2011 telephone and email interview with Bonnie Anderson, Chief Executive Officer of Veracyte, and Richard Lanman, MD, Chief Medical Officer.

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Baloch ZW, et. al. "Diagnosis of "follicular neoplasm": a gray zone in thyroid fine-needle aspiration cytology. " Diagn Cytopathol. 2002;26:41

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Haugan BR, et al. Abstract #LB137, International Thyroid Congress. Paris, FR 2010 (oral abstract).

Ladenson PW, et al. "Poster presented at ENDO 2010: The 92nd Annual Meeting & Expo." San Diego; 2010.

Li, Henry et. al. "Cost-Effectiveness of a Novel Molecular Test for Cytologically Indeterminate Thyroid Nodules." Journal of Clinical Endocrinology and Metabolism. Published online before print August 24, 2011, Scheduled for November 2011 print publication. Abstract

Raber W, et. al. "Risk factors for malignancy of thyroid nodules initially identified as follicular neoplasia by fine-needle aspiration: results of a prospective study of one hundred twenty patients." Thyroid. 2000;10:709

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