Novel Sputum Tests May Help Detect Lung Cancer Early

Barbara Boughton

August 7, 2009 (San Francisco, California) — Early detection of lung cancer remains one of the challenges of modern medicine. One method for early detection — sputum analysis — is plagued by inconsistent results and a high false-negative rate. Two new tests for lung cancer cells in sputum aim to improve the sensitivity and specificity associated with slide-based review, according to research presented here at the 13th World Conference on Lung Cancer, organized by the International Association for the Study of Lung Cancer (IASLC).

One of the testing methods is a device that produces 3D images of cells in sputum and distinguishes normal from abnormal cells on the basis of a variety of morphology characteristics. The other test analyzes sputum cells for 3 methylation markers that are signals of lung cancer.

The 3D test, called the Lung Cell Evaluation Device (LuCED), developed by VisionGate, uses a process that dissolves mucous in sputum, making it easier to work with the remaining cells. Cells are collected in clusters, imaged in 3D, and analyzed for more than 25 different features that can indicate how abnormal they are. These features include cell volume, cell shape, nuclear/cytoplasmic volume, and nuclear or chromatin distribution. The device then assigns a score to each specimen of cells, with higher scores indicating dysplasia or cancer. About 1000 cells are processed to obtain each score, said researcher Michael Meyer, MS, vice president for image engineering at VisionGate.

In collaboration with the University of Washington, VisionGate researchers analyzed sputum samples from more than 400 patients with confirmed lung cancer. They found that their technology had 100% specificity and 90% sensitivity, Mr. Meyer said. "This is an extremely valuable technique that could be used in many different applications. Our goal [is] to provide critical information to clinicians for follow-up," he added. Plans call for LuCED to be commercialized for lung cancer testing by 2011. By that time, researchers estimate that the technology will be able to process each specimen in about 20 minutes; it now takes about a day.

"The sensitivity of the test is very high," noted former IASLC board member Masahiro Fukuoka, MD, PhD, from Kinki University School of Medicine in Osaka, Japan. "This 3D analysis could provide high sensitivity and consistency in diagnosis of dysplastic and cancer cells. It could be a new diagnostic standard," he added.

In other research presented at the meeting, Dutch scientists explored the relation between methyl groups in sputum and lung cancer, which could be used to devise a noninvasive and more accurate diagnostic test. The researchers selected 3 promising marker genes that could signal the presence of lung cancer — RASSF1A, CYGB, and APC — and examined sputum samples of 570 lung cancer patients for these markers. They found that using the 3 methylation markers together, their tests had 60% sensitivity and 90% specificity. When tests for RASSF1A and conventional cytology were combined, their tests had 54% sensitivity and 98% specificity.

"Sputum methylation was detected even in sputum samples from patients with lower-stage lung cancers," said lead researchers Erik Thunnissen, MD, from Pathologisch Anatomisch Laboratorium in Amsterdam, the Netherlands.

Although acknowledging the superior sensitivity and specificity of the Dutch researchers' methylation testing, Stephen Lam, MD, from the British Columbia Cancer Agency in Vancouver, cautioned that these tests may be a long way from being practical for lung cancer screening. Dr. Lam, who moderated the session at which the Dutch paper was presented, noted that the samples being analyzed came from patients with clinically diagnosed lung cancer, and that the tests could perform differently in a screening setting.

"We need to look at the incremental value of these biomarkers and integrate clinical data with this kind of analysis. In that way, biomarker tests are likely to be improved further," he said.

Mr. Meyer is an employee of VisionGate. Dr. Fukuoka, Dr. Thunnissen, and Dr. Lam have disclosed no relevant financial relationships.

13th World Conference on Lung Cancer (WCLC): Abstracts D1.3 and D1.5. Presented August 4, 2009.