NEW GENOMIC TEST INCREASES BRONCOSCOPY SENSITIVITY

A new genomic test may be able to improve the diagnostic performance of bronchoscopy and help avoid the need for more invasive procedures in patients with suspected lung cancer.

"This test can change clinical practice in pulmonary medicine," commented senior author Avrum Spira, MD, professor of medicine at Boston University School of Medicine, in Massachusetts, who is the coinventor of the test. "It allows physicians to confidently identify patients who are at low probability for having lung cancer following an indeterminate bronchoscopy result."

The Percepta Bronchial Genomic Classifier (Veracyte) is a bronchial-airway gene-expression classifier. Results of two large studies show that this genomic test can help pinpoint which patients with suspicious lung lesions may be able to safely avoid lung biopsies.

The results of both studies were presented at the American Thoracic Society 2015 International Conference, being held in Denver, Colorado, and were published concurrently online in the New England Journal of Medicine.

With the advent of the use of low-dose CT in the screening of patients at high risk for lung cancer, more suspicious lesions are being detected. The next step for these patients is a bronchoscopy. Following these two procedures, patients are then assessed as being at high, intermediate, or low risk for cancer. "The sweet spot for the test," Dr Spira told Medscape Medical News, "is the intermediate-risk group."

"While the test did well across all groups, the most difficult cases are where the physician is not sure what the next step is," he said.

Low-risk patients may just need to be followed closely and have repeat scans, whereas a biopsy would be indicated for high-risk patients. But for patients at intermediate risk, it is not as clear, Dr Spira explained. "And this is the group where the test had the biggest impact in clinical decision making. It had a negative predictive value of 91%, and these results provide an opportunity for patients to be monitored using CT scans instead of having to go undergo biopsy."

Accurate Diagnosis of Cancer

The test is a 23-gene molecular classifier that can detect molecular changes in the epithelial cells that line the respiratory tract. Cells are obtained from cytology brushings taken during bronchoscopy from the proximal airway.

Dr Spira and colleagues undertook the two studies to prospectively validate this classifier in patients undergoing bronchoscopy for suspected lung cancer and also to evaluate whether its use could change the diagnostic performance of bronchoscopy.

The cohort included current or former smokers who were undergoing bronchoscopy for suspected lung cancer at 28 different centers. A total of 639 patients in AEGIS-1 (298 patients) and AEGIS-2 (341 patients) met the criteria for inclusion. A genomic analysis was conducted in epithelial cells that were collected from the normal-appearing mainstem bronchus to assess the probability of lung cancer.

In AEGIS-1, the classifier accurately identified 194 of 220 patients with cancer (sensitivity, 88%; 95% confidence interval [CI], 83 to 92) and 37 of 78 patients without cancer (specificity, 47%; 95% CI, 37 to 58).

For the AEGIS-2 study, results were similar. The classifier correctly identified 237 of 267 patients with cancer (sensitivity, 89%; 95% CI, 84 to 92) and 35 of 74 patients without the disease.

In patients with a nondiagnostic bronchoscopic examination, the classifier accurately identified cancer in 49 of 57 patients in AEGIS-1 (sensitivity, 86%; 95% CI, 74 to 94) and in 58 of 63 patients in AEGIS-2 (sensitivity, 92%; 95% CI, 82 to 97).

False Negatives

Although the classifier achieved a high negative predictive value in patients with a nondiagnostic bronchoscopic examination, the authors note that 13 patients in this group had a false negative result. Although they had lung cancer, they had a negative classifier score. The majority of them (10 of 13) had a high (>60%) probability of cancer; three patients had an intermediate (10% to 60%) pretest probability of cancer.

There are going to be some false negatives, Dr Spira pointed out. "But the patients are followed and will have repeat scans."

The test is already on the market, but the initial release was limited to only about 30 centers through an early access program, he said. "It was a soft launch, and will soon be more readily available."

It can be performed in any facility in which bronchoscopies are performed. Samples are sent to a central laboratory to be analyzed.

The study is funded by Allegro Diagnostics and by grants from the National Institutes of Health, the Department of Defense, and the National Cancer Institute. Dr Spira is a coinventor of the genomic test; several of the authors have listed potential conflicts of interest, including relationships with Allegro.