NEW YORK (GenomeWeb) —Studies presented this week at the International Thyroid Congress and Annual Meeting of the American Thyroid Association (ITC/ATA) demonstrated clinical validation or long-term utility of molecular thyroid nodule classifier tests from Veracyte, Interpace Diagnostics, and Rosetta Genomics.
All three companies' tests are designed to help physicians make better-informed decisions in regards to indeterminate fine needle aspiration cytopathology results. According to the American Thyroid Association, 15 to 30 percent of all thyroid nodule cytopathology results are indeterminate. Many patients with indeterminate results undergo invasive surgeries that are later proved unnecessary, as the nodules prove benign.
Veracyte's Afirma Gene Expression Classifier (GEC), has been on the US commercial market since 2011, has been clinically validated in several large studies, and has obtained widespread physician and payer adoption, as well as inclusion in leading clinical practice guidelines. This classifier is a 142-gene molecular test that identifies benign thyroid nodules among those deemed indeterminate by cytopathology. It scans samples using Affymetrix Gene Chip systems and uses proprietary Veracyte software (VTM 0.2.0) to analyze the 142 different genes that have been determined to demonstrate a recognizable pattern of expression in benign thyroid nodules.
The studies presented this week at ITC/ATA demonstrated the long-term clinical utility of Afirma GEC in safely reducing the number of unnecessary thyroid surgery. In the first study, researchers used the Integrated Research Database from Anthem subsidiary HealthCore to compare outcomes during follow-up of 201 patients with benign Afirma GEC results to a matched control group of 603 patients with benign cytopathology results. Over an average follow-up period of 20 months, Afirma GEC-benign patents were no more likely to undergo thyroid surgery than the control group (11 percent vs. 10 percent). The rate of ultrasound follow-up examinations was also similar among the Afirma GEC-benign patients (60 percent), compared to the cytopathology-benign group (62 percent).
"Our findings suggest that use of the Afirma GEC could change the trajectory of care for many of those patients, enabling them to stay out of the operating room," Joseph Singer, lead author on the study and chief medical officer of Healthcore, said in a statement.
In the second study, researchers assessed surgery rates for Afirma GEC-benign patients who were tested at 16 community-based practices and followed for three years. They found that 81 out of 98 patients (about 83 percent) with a benign Afirma GEC result avoided surgery during 36 months of follow-up. The historical rate of surgery avoidance is only 26 percent for patients with cytopathology-indeterminate nodules.
"The new data presented today highlight the profound, real-world impact that the Afirma GEC is having on clinical decision-making in thyroid cancer diagnosis," Bonnie Anderson, president and CEO of Veracyte, said in a statement. "We believe these findings further add to the growing library of clinical evidence supporting the continued adoption and reimbursement of the Afirma GEC." To date, the Afirma GEC is covered for approximately 150 million Americans through their insurers.
In another ITC/ATA presentation, Rosetta Genomics announced the completion of a multicenter, blinded validation study of its microRNA-based diagnostic assay for the classification of indeterminate thyroid nodules and announced the launch of its assay on the market under the name RosettaGX Reveal.
The assay analyzed highly purified RNA samples from FNA smears, collected from seven medical centers, through next-generation sequencing and proprietary qPCR. A set of 96 microRNAs was selected based on microarrays and next-generation sequencing studies and confirmed in over 200 FNAS using qPCR. After profiling, a set of 24 microRNAs including malignant, benign, epithelial, and blood markers was selected for subsequent training studies.
The validation study was conducted on 203 fine needle aspiration smears collected from centers in the US, Europe, and Israel. Of the 203 smears, 192 (94.6 percent) passed quality assurance measures. All samples were processed according to standard operating procedures by personnel blinded to the reference diagnosis, and classifications were automatically generated by a dedicated software algorithm.
Performance data from the study, confirmed by three pathologists, demonstrated that the assay has a sensitivity of 95 percent, specificity of 79 percent, negative predictive value of 98 percent, and positive predictive value of 63 percent. The overall sample set, where the final diagnoses were agreed to by at least two pathologists, demonstrated a sensitivity of 84 percent, specificity of 72 percent, NPV of 90 percent, and PPV of 60 percent.
Nicole Massoll, a medical director of cytopathology at the University of Arkansas for Medical Sciences and at FNApath laboratories who was not involved in the study, commented in a statement that the performance data are impressive, especially with regard to the NPV of 98 percent achieved for the samples on which three expert pathologists agreed on the final diagnosis. A high NPV is important because patients with indeterminate nodules are often referred to surgery, though most of these nodules prove to be benign.
RosettaGX Reveal offers a valuable tool for the classification of preoperative thyroid samples and is the only assay that can utilize cytology smears, the company said. It is also the first commercial test that interrogates the same thyroid cells that the cytopathologist viewed for the initial indeterminate diagnosis, Rosetta added
"We remain confident this will be an important product for our portfolio as practice guidelines already recognize the value of molecular profiling in cases where the initial diagnoses for an FNA thyroid smear is indeterminate," Kenneth Berlin, president and CEO of Rosetta Genomics, said in a statement. "This fact, combined with the obvious health economic benefits this test will bring by avoiding unnecessary surgeries, creates prime market conditions that should encourage market adoption."
Finally, Interpace Diagnostics, a PDI subsidiary, announced results from two studies validating the utility of the combined use of its ThyGenX oncogene panel and ThyraMIR microRNA classifier, both of which are commercially available in most US states.
Interpace Diagnostics' ThyGenX thyroid oncogene panel test uses next-generation sequencing to identify more than 100 genetic alterations associated with papillary and follicular carcinomas, the two most common forms of thyroid malignancies. The test assists physicians in distinguishing between benign and malignant genotypes in indeterminate thyroid nodules.
ThyraMIR Thyroid miRNA Classifier measures the expression of 10 microRNAs and, when used in combination with ThyGenX, yields both high negative predictive value and high positive predictive value. This results in improved molecular classification of both benign and malignant thyroid nodules independent of thyroid cancer prevalence in the clinical setting, the company said.
The first study analytically validated the two tests use on fixed nodule specimens, including formalin-fixed paraffin-embedded samples, cytology slides, and ThinPrep slides, in addition to the current molecular analysis of fine needle aspirations. The ability to analyze these types of samples allows for molecular evaluation of older archived samples. An additional benefit is that this expanded menu of molecular testing on cytology slides and ThinPrep sample types can potentially eliminate the need for a second needle pass during patient biopsy.
The second study presented further validated the utility of combining ThyGenX and ThyraMIR. When used in combination, ThyGenX and ThyraMIR showed performance improvements over each test individually. This results in increased diagnostic sensitivity which in turn improves the preoperative diagnosis of thyroid nodules with indeterminate cytology.
"We are pleased to announce this growing body of evidence supporting the power of our thyroid nodule combination testing," Nancy Lurker, PDI's CEO, said in a statement. "In addition, the analytical validation supporting the evaluation of FFPE and cytology slides will mean more widespread thyroid nodule molecular testing will be available to physicians and patients. As a result of these data we plan to offer commercial cytology testing services in the near future as we continue to expand our diagnostic offerings."