Miriam E Tucker

May 17, 2015

Nashville, Tennessee — A newly available combination molecular testing platform accurately distinguishes between benign and malignant thyroid nodules among those initially deemed indeterminate, a study finds.

Validation data for the ThyraMIR microRNA gene-expression classifier combined with the genetic-mutation panel ThyGenX (Interpace Diagnostics) were published online May 12, 2015 in the Journal of Clinical Endocrinology and Metabolism, and additional data were presented in two posters here at the American Association of Clinical Endocrinologists' 2015 Annual Scientific and Clinical Congress by Emmanuel Labourier, PhD, from BMDx Consulting, Austin, Texas, formerly with Asuragen, the company that originally developed part of the technology.

"One of the key challenges is when you have a suspicious nodule, you have to determine whether it's benign or malignant to determine if the patient has to go to surgery. After fine-needle aspiration, about 20% to 30% are indeterminate. What we have done is come up with a new approach, which is a combination test — for the first time, we are able to both rule in and rule out malignancy," Dr Labourier told Medscape Medical News.

Reducing the Number of Unnecessary Surgeries

In the study, results from the combination test were compared with surgical histopathology for 109 thyroid nodules from 12 US endocrine practices. The nodules had been classified preoperatively as either atypical of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS, Bethesda category III) or follicular neoplasm/suspicious for a follicular neoplasm (FN/SFN, Bethesda category IV).

Among the 35 nodules with a confirmed malignant outcome, 24 were positive by the mutation testing and 20 were positive by the microRNA classifier. The combined test had a 94% negative predictive value, 74% positive predictive value, 89% sensitivity, and 85% specificity.

Independently of variations in cancer prevalence, the test increased the yield of true benign results by 65% relative to mRNA-based gene-expression classification and decreased the rate of avoidable diagnostic surgeries by 69%.

"Right now, too many people go to diagnostic surgery with an indeterminate nodule, when in fact they don't have cancer. You expose people to potential complications.…There is a lot of risk. What you want to do is reduce the number of unnecessary surgeries. For that, you need a test that has a high negative predictive value. That's what we achieve by combining these two tests together," Dr Labourier said.

More Validation Required in Larger Numbers of "Real-World" Patients

Asked to comment on the data, AACE immediate past president R Mack Harrell, MD, from Memorial Healthcare System, Hollywood, Florida, cautioned that more validation is needed in real-world settings with larger numbers for this new platform, as well as for other "next-generation" molecular tests such as the ThyroSeq that was developed at the University of Pittsburgh and is now available through CBLPath.

"So much of the predictive value of these tests depends on what you start with. If you start with a highly selected tertiary-care-referral cancer community, the efficacy of the test is completely different from starting with a practice that's receiving every thyroid nodule in town. So, it needs to be tested in a true community-practice-type setting with lots of patients before you can be sure exactly how it's going to perform."

He added, "That's why it's important for people in private practice to work out agreements with the company and use the technology and report what happens when they use it."

Indeed, that's what Dr Harrell's Florida-based endocrine surgery practice did when the Afirma Gene Expression Classifier came out about 5 years ago.

They reported their results at international meetings and published them in Endocrine Practice (Endocr Pract. 2014;20:364-369). The conclusion from their paper: "In a practice with a high incidence of thyroid cancer in patients with indeterminate [fine-needle aspirations] (33% for our practice), the [negative predictive value] of the Afirma GEC test may not be as robust as suggested in the existing literature."

Dr Harrell told Medscape Medical News, "I think we added to the knowledge of the practicing physician. The same thing needs to happen with this."

An Interpace Diagnostics spokesperson told Medscape Medical News that the combination test is priced comparably to others on the market, and the company is currently working with payers to establish reimbursement. In the meantime, a patient-assistance program is available to defray the cost.

Dr Labourier is a paid consultant to Interpace Diagnostics, which funded the study. Dr Harrell has no disclosures.

J Clin Endocrinol Metab. Published online May 12, 2015. Abstract

American Association of Clinical Endocrinologists' 2015 Annual Scientific and Clinical Congress. May 13-17, 2015; Nashville, Tennessee. Abstracts 1086 and 1095.

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