Respiratory Mucous Test Analyzing Genetic Biomarkers Can Detect Early Lung Cancer

In In The News by Barbara Jacoby

By: Robert Glatter, MD

From: forbes.com

Non-small cell lung cancer (NSCLC) is the most common cause of lung cancer deaths in the U.S., and resulted in a fatal outcome for close to 160,000 people in 2014.

Since early treatment can effectively improve patient outcomes, low dose CT scans are currently being used by healthcare providers to detect early lung cancers before they produce symptoms in patients who have a heavy smoking history, and consequently are at increased risk for developing lung cancer.

Yet, low dose CT screening, while effective, is costly, requires extensive time, and frequently results in overdiagnosis since it often identifies lesions which are non-cancerous or benign, solitary pulmonary nodules, along with cancerous nodules.

But whether CT scanning is the best initial approach to distinguish higher risk nodules from benign nodules before they develop into full blown cancer and metastasize is the more important question. The development of an accurate and noninvasive test as first step prior to CT scanning would offer many advantages for patients.

As a result of new research,those who have smoked for many decades and are consequently at risk for developing lung cancer can now benefit from a new noninvasive, sputum-based (respiratory mucous) test that can determine if a lung nodule is malignant or benign.

The assay which evaluates sputum, or mucous from the respiratory tract, for genetic signs of lung cancer was able to differentiate benign lung nodules from early stage lung cancer close to 80 percent of the time in a recent study.

The research was published online January 15, in the Journal, Clinical Cancer Research.

“We are facing a tremendous rise in the number of lung nodules identified because of the increasing implementation of the low-dose CT lung cancer screening program,” said Feng Jiang, M.D, PhD., an associate professor in the Department of Pathology at the University of Maryland School of Medicine in Baltimore. “However, this screening approach has been shown to have a high false-positive rate. Therefore, a major challenge is the lack of noninvasive and accurate approaches for preoperative diagnosis of malignant nodules.

According to Jiang, however, evaluating sputum or respiratory mucous for a panel of three microRNA (miRNA) biomarkers was able to successfully differentiate early-stage lung cancers from nonmalignant nodules the majority of the time.

Jiang and colleagues first evaluated the miRNA sputum biomarker panel in a group of 122 patients who were noted to have a lung nodule after having a CT scan. The test was 83 percent accurate in correctly identifying those who actually had lung cancer present in their nodule. It was also 88 percent correct in identifying those who did not have lung cancer in their nodule.

Among two additional groups of patients evaluated with the same biomarker panel, rates of 82 percent and 88 percent, 80 percent and 86 percent, were achieved respectively.

However, these rates are not accurate enough both for detection and ruling out cancer, according to Jiang.

“These values for sensitivity and specificity are not high enough for the three-biomarker panel to be used in the clinic,” said Jiang. “Because the specificity is only 87 percent, we cannot be certain enough that a patient does not have lung cancer. To be nearly certain whether a patient does or does not have lung cancer, the specificity of a test should be close to 100 percent.”

Jiang explains that “before these results can be translated into the clinic, we need to identify other biomarkers to add to the existing panel, to increase its sensitivity and specificity, and need to evaluate the panel in a prospective clinical trial.”

“We are now applying new technologies to identify additional miRNA sputum biomarkers of lung cancer with the goal of expanding our biomarker panel to generate a test with high efficiency that can be practically used in clinical settings for lung cancer early detection,” added Jiang.

So the question is whether sputum biomarkers may hold potential to reduce the need for CT scanning in patients at highest risk for lung cancer, who demonstrate a suspicious nodule on CT imaging. Jiang believes that this technology does hold promise in this respect.

“The biomarkers may function as a cost-effective assay at the first screening to pre-identify smokers at the highest risk for lung cancer,” said Jiang. “Subsequently, specifically screening the pre-identified individuals with a smaller population size by using CT [that is more expensive] could significantly and cost-effectively help diagnose lung cancer earlier in smokers.

One certain advantage, Jiang explains, is that “Physicians practicing general medicine could take advantage of this simple test for risk assessment that is able to classify the general population according to their lung cancer risk in a personalized manner.”

Another question is whether using biomarkers could ever become a viable method of surveillance to monitor for cancer recurrence after a treatment regimen has been initated.

Jiang is doubtful, explaining that it is unclear whether “the sputum biomarkers used for early detection of cancer can be used for monitoring lung cancer recurrence after a treatment regimen.”

Jiang certainly is confident that widespread adoption of such technology–if it becomes refined and validated in further validation trials–could certainly reduce healthcare costs‎, let alone radiation exposure.

Another issue is whether there may be a way in the future to integrate such technology into a specialized device attached to a smartphone for use with an app, so that patients could place a sample on a device which could then analyze the sample, and subsequently upload data to a cloud based application for final analysis.

Jiang believes that such a sputum-based assay would likely work in a smartphone–just as a drop of blood would work in a similarly designed assay.