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New test may prevent invasive procedures and save lives

“The ability to test for molecular changes allows us to catch or rule out the disease earlier, without invasive procedures,” says BU School of Medicine professor Avrum Spira, who co-developed a genetic early-warning test for lung cancer. Photo by Vernon Doucette

Lung cancer is responsible for the most cancer deaths in the United States. According to the National Cancer Institute, it will kill an estimated 158,000 people in 2015, more than breast, prostate, and colon cancer combined. Because lung cancer grows and spreads so quickly, many healthy (and former) smokers undergo diagnostic screening CT scans of the chest, which can detect small lesions in the lungs that may be an early sign of the disease. But abnormal results often lead to painful and invasive biopsies. Now, Avrum Spira has found a better path to diagnosis.

For more than a decade, Spira, a Boston University School of Medicine (MED) professor of medicine, pathology and laboratory medicine, and bioinformatics, has been developing molecular tests to detect lung cancer early, without invasive biopsies. The work has been done together with Jerome Brody, MED professor of medicine, and Marc Lenburg, MED associate professor of medicine. In May 2015, the molecular diagnostics company Veracyte, Inc. released a new, noninvasive test for the disease based on biomarkers developed by Spira and his collaborators. The test, called Percepta™, fared well in clinical trials and could be available to patients in less than a year. The results of the trials were announced in the New England Journal of Medicine on May 17, 2015.

Spira, who is also a pulmonologist at Boston Medical Center, has wrestled firsthand with the difficulty of early detection. “It’s a growing problem in our clinical pulmonary practices: smokers, either current or former, have something abnormal found on a CT scan of the chest, and we’re worried it might be lung cancer,” he says. A doctor may follow up with a bronchoscopy, a minimally invasive outpatient procedure that allows the doctor to examine a patient’s airways with a flexible tube.

While bronchoscopy is a useful tool, it’s not always effective at finding small tumors that are buried deep within the lung. “So often we don’t get a diagnosis,” says Spira, “and then we don’t know what to do next: to biopsy it or not.”

When a bronchoscopy is inconclusive, doctors and patients often err on the side of caution, opting for a lung biopsy—either via CT-guided needle biopsy or surgery. About one-third of lung biopsies come back negative. “So one-third of the time we’re taking a piece out of someone’s lung unnecessarily,” says Spira. “That can have complications for the patient and obviously has huge costs to the health care system. Our test can identify which patients don’t have lung cancer, and therefore don’t need that procedure.”

PerceptaTM early lung cancer detection device

During the Percepta test, which is performed at the same time as a bronchoscopy, the doctor uses a small brush to sample normal-looking cells in the upper airway, which are then sent to a lab for genetic testing. Spira discovered that these cells, while appearing healthy, are in the “field of injury” damaged by cigarette smoke and contain genomic markers that signal a high likelihood of cancer elsewhere in the lung. The 23 markers in the test indicate different things: some show protective genes being turned off, while others show genes associated with cell growth being turned on.

“The ability to test for molecular changes in this ‘field of injury’ allows us to catch or rule out the disease earlier, without invasive procedures,” says Spira. “Conceptually, this has implications for other diseases.”

The genomic markers were validated in two clinical trials, involving 639 patients at 28 sites in the United States, Canada, and Ireland. Researchers collected upper airway cells from people who were undergoing a bronchoscopy, then checked them one year later to see if they had been diagnosed with lung cancer. The Percepta test, when used in conjunction with bronchoscopy, identified 97 percent of the lung cancers, compared to 75 percent for bronchoscopy alone. “Our test showed very high sensitivity for detecting lung cancer in both studies,” says Spira. “So if the test is negative, that gives you a high level of confidence that person does not have lung cancer.”

The Percepta test is not yet widely available, nor is it covered by insurance. Veracyte has launched the test in an early access program, offering it in a limited number of medical centers in the United States to gather feedback on how the test is used and its clinical impact. If this trial launch is successful, the Percepta test could be made widely available in early 2016.

For Spira, it’s been gratifying to see the work he began over a decade ago finally helping patients. “Just knowing that somebody may benefit from the product, that’s the most satisfying piece,” he says. “It’s really about impacting patient care and helping people.”

This BU Research story was written by Barbara Moran.

Source: Boston University School of Medicine

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