Outlet Full Name: Med Page Today
Author: Crystal Phend
Gene analysis of the bronchial airway could reduce unnecessary invasive testing for suspected cases of lung cancer, a study suggested.
A 17-gene test for normal epithelial cells gathered on bronchoscopy boosted the ability of that procedure to rule out cancer, Duncan Whitney, PhD, of test developer Allegro Diagnostics in Maynard, Mass., and colleagues found.
It had a negative predictive value of 93% for patients with nondiagnostic bronchoscopy, they reported here at the American Thoracic Society meeting.
If the test results had been used to rule out cancer, 42% of further invasive procedures for lesions ultimately found to be benign could have been avoided, Whitney told attendees at the late-breaking trial session.
Finding ways to cut down on the harms associated with lung cancer screening, such as unnecessary invasive testing and surgery, is crucial, Albert J. Polito, MD, chief of pulmonary medicine at Mercy Medical Center in Baltimore, noted.
Those not only add to cost but morbidity and anxiety and appear to have played into the decision of an advisory panel last month to recommend against Medicare reimbursement for lung cancer screening, he noted.
“If we had some other piece of information that could help to sway the benefit toward the fact that we can really be more certain about ruling out the false positives, that would be great,” he told MedPage Today.
Other options are under development as well, such as PET scans, risk factor algorithms, and biomarkers.
The test (BronchoGen) measures gene expression as a measure of smoking-related damage in cytologically normal cells, not necessarily reflecting of biology of the suspected lesion itself, Whitney noted.
The AEGIS 1 (Airway Epithelium Gene Expression in the Diagnosis of Lung Cancer) study included mainstem bronchus cell samples from 597 current or former smokers scheduled for bronchoscopy at 25 medical centers.
Among them, 74% were diagnosed with lung cancer by pathology as the gold standard. The rest are being followed for 12 months to confirm cancer-free status if no malignancy was initial diagnosed, although those results aren’t available yet.
In the randomly selected half of patients in the validation set, bronchoscopy had a sensitivity of 74% and specificity of 100%.
In cases where bronchoscopy indicated no cancer, genomics had a sensitivity of 86% and specificity of 47%. Whitney noted that the threshold was set to maximize sensitivity with the primary goal of accurately ruling out cancer.
Together, the two tests had a sensitivity of 96% and specificity of 47%.
The addition of genomics reduced the negative likelihood ratio of bronchoscopy from 0.260-0.077.
For patients with a pretest probability of cancer less than 0.66, the posttest probability dropped to less than 10%.
Accuracy was independent of lesion size and location categories, with the greatest improvement in diagnostic yield over bronchoscopy alone in small peripheral lesions for which bronchoscopy is least sensitive, Whitney noted.
A second validation set in the 341-sample AEGIS 2 study showed “equivalent” performance, he noted.
However, session co-moderator R. Graham Barr, MD, MPH, DrPH, of Columbia University in New York City, pointed out that knowing the population from whence the results came is important in considering a negative predictive value.
Whitney acknowledged that the set of patients considered for enrollment in the AEGIS trials wasn’t consecutive patients and noted that the negative predictive value was based on a 50% prevalence of lung cancer in clinical practice.
His company plans to launch the test as a Clinical Laboratory Improvement Amendments (CLIA) lab service once the results are published, he said.