3D Imaging Test Developed for Managing Lung Cancer Screen False-Positives

A landmark 53,000-person study demonstrated that low-dose computed tomography (CT) screening of high-risk individuals decreases lung cancer deaths by 20%. However, CT scans generate high rates of false-positive findings--nearly one in four--requiring invasive, expensive follow-up. A new noninvasive three-dimensional (3D) imaging test can identify early stage lung cancer cells in sputum with high sensitivity and specificity.

VisionGate, Inc. (Phoenix, AZ, USA), a company developing a revolutionary noninvasive test for the early detection of lung cancer, recently presented data showing how adjunctive use of its LuCED test can improve the utility of low dose X-ray computed tomography (CT) screening for the early detection of lung cancer in high risk individuals. LuCED uses VisionGate’s innovative automated 3D cell imaging platform, the Cell-CT, which generates high-resolution 3D biosignatures from intact cells using a sputum sample. The data were presented at the International Association for the Study of Lung Cancer’s 14th World Conference on Lung Cancer on July 7, 2011, held in Amsterdam, The Netherlands.

The proposed first use of LuCED as an adjunct to CT screening reflects the results of the US National Cancer Institute’s (NCI; Bethesda, MD, USA) landmark National Lung Screening Trial (NLST) of more than 53,000 current and former heavy smokers, which revealed that low-dose helical CT screening reduced lung cancer deaths by 20% compared to standard chest X-rays. These findings were first presented November 2010 and were expanded in the June 29, 2011, online edition of the New England Journal of Medicine (NEJM).

The NLST findings are generating widespread interest in the broad use of CT screening as a way to reduce lung cancer deaths in high-risk populations. However, the utility of the approach is hampered by the high rate of false positive results seen in the study--according to the NCI, more than 96% of the positive findings from low-dose CT screening over three rounds of testing turned out to be false-positive findings, representing almost a quarter (23.3%) of the overall test results. These false-positive test results require follow-up care that results in unnecessary invasive procedures for many patients and considerably higher costs for the healthcare system as a whole, potentially jeopardizing the feasibility of implementing mass screening programs for the millions of individuals at high risk for lung cancer.

In its presentation, VisionGate showed how LuCED harnesses the power of 3D imaging to detect cancer cells accurately when present in sputum samples from individuals at high risk of lung cancer. The presentation outlined patient management protocols for the noninvasive and efficient use of LuCED as an adjunct to CT screening to confirm which cases are true positives and to lower significantly the number of cases which are false positives.

Dr. Claudia Henschke, a lung cancer researcher at the Biodesign Institute at Arizona State University (Phoenix, USA), who is also a practicing physician at Mount Sinai Medical Center (New York, NY, USA), serves as a leader of the International Early Lung Cancer Action Program. She is coauthor of a pioneering study of the benefits of CT scans for lung cancer that was published in NEJM in 2006.

Dr. Henschke noted, “Today, almost all patients diagnosed with lung cancer in the US die. The NLST study results released last November confirmed our initial findings showing that CT scans can find lung cancers in their earliest stage, when up to 92% can be cured. VisionGate’s LuCED technology has demonstrated promise as an approach that may increase the feasibility of implementing widespread screening of high risk individuals, initially being used as an adjunct to improve the accuracy of CT scan results, with the potential to be used as a primary screening tool if additional trials are successful. We look forward to the opportunity to contribute to assessments of its potential utility in helping to reduce the death rate from this lethal cancer that affects so many people around the globe.”

LuCED uses the company’s breakthrough automated Cell-CT platform to generate detailed 3D images of the cells contained in sputum samples, which the system analyzes to identify key features associated with potential malignancy. The analysis yields a score that indicates whether or not cancer cells are present in the sample. The Cell-CT system produces strikingly clear and comprehensive 3D images of the cells, enabling extremely accurate classifications. VisionGate researchers estimate that LuCED will be able to achieve specificity of 99% and sensitivity of 75% in actual use.

“The dramatic results of the NLST study provide us with a valuable initial indication for our LuCED test,” commented Scarlett Spring, president of VisionGate. “By combining the high accuracy and cost effectiveness of our noninvasive LuCED diagnostic with the proven ability of CT screening to reduce lung cancer deaths, we hope to make mass screening feasible and affordable. We believe that we have developed an efficient clinical and regulatory strategy for our proposed use of LuCED to manage the false-positive results from CT screening, and we look forward to advancing this program in the coming months.”

Prior to the development of LuCED, a number of studies had validated that analyzing cells in sputum could potentially be useful in the early detection of lung cancer, revealing that 85% of sputum samples from individuals with lung cancer (the samples were taken over three days and pooled) actually contained cancer cells. However, the typically poor sensitivity of raw sputum analysis and the labor-intensive nature of the process made it impracticable for widespread use in lung cancer screening. The Cell-CT platform’s 3D technology, combined with its advanced automated 3D image analysis algorithms, for the first time make a cell-based sputum analysis approach both logistically feasible and cost effective.

VisionGate is developing the noninvasive test for the early detection of lung cancer, using its automated 3D cell-imaging platform, the Cell-CT, which generates high-resolution 3D biosignatures from intact cells using a sputum sample. The company’s LuCED test is initially being developed for adjunctive use with low dose CT screening for the early detection of lung cancer in high-risk individuals. Adjunctive use of LuCED to manage better the high rate of false-positive results in CT screening could increase the utility and cost effectiveness of the approach, which has been shown to decrease lung cancer deaths in former and current smokers.

Related Links:
VisionGate
US National Cancer Institute