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Diagnostic tools and innovative therapies improve patient prognosis

SAN FRANCISCO, August 2, 2009 The world's top lung cancer specialists, medical professionals and researchers are convening this week in San Francisco, CA for the 13th World Conference on Lung Cancer (WCLC), organized by the International Association for the Study of Lung Cancer (IASLC). Prevention and early detection of cancers translates to better prognoses, but lung cancer remains one of the hardest cancers to detect in its early stages. According to research highlighted today at WCLC, innovative diagnostics and treatments using naturally occurring and synthetic human compounds can help detect early stage lung cancer and treat at-risk patients to prevent cancer cell progression.

"Identifying and treating at-risk patients smokers, ex-smokers and non-smokers exposed to environmental triggers before cancer cell presentation will reduce incidence of one of the leading causes of death worldwide," said David Gandara, M.D., WCLC program chair. "While our main focus continues to be prevention, new diagnostics to detect early stage lung cancer are paramount to improving patient survival rates."

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Recent studies have shown that specific volatile organic compounds (VOCs), gasses emitted from certain solids or liquids such as paint, are present in the breath of lung cancer patients and analysis of these compounds could lead to new diagnostic tools for patients.

The origins of these VOCs are still up for debate. It is unknown if they emerge from the tumor itself, its micro-environment or if they are produced by the human as a reaction to the tumor. Researchers sought to answer this question by comparing non-small cell lung cancer (NSCLC) cell lines and examining their production of VOCs.

Ten adenocarcinoma (AC) and two squamous cell carcinoma (SCC) cell lines were grown in standard conditions and compared to control. Gas-chromatography mass spectrometry was used to examine the chemical nature of the cancerous VOCs and an electrical nose device detected the difference between cancerous cells and the samples.

In the study, 350 to 400 different VOCs were identified in either tumor cells or controls. The analysis revealed 120 of the compounds appeared in all tumor and control cells with a high confidence interval (>89 percent). Of those 120 compounds, five were found to be present in all tumor cells but not in the control group, and three of those were present specifically in the exhaled breath of NSCLC patients. The three compounds that were present in exhaled breath were found in more than 90 percent of NSCLC patients.

Given this finding, researchers were able to conclude that VOCs transfer to the breath of patients via a metabolic pathway present in the tumor cells.

"Now that we have a better understanding of the origin of these compounds and have pinpointed their presence with a large degree of accuracy, we hope to use this information to develop a test that examines the exhaled breath of patients for early detection of lung cancer," says Nir Peled, M.D., lead author of the study, and Fulbright Scholar at the University of Colorado Cancer Center. "This research is a promising step toward an earlier, more accurate and cost-effective diagnosis for lung cancer patients."

Dr. Peled will present this study on Sunday, August, 2, 3:20 pm PT in Moscone West, Room 2016-2018, Level 2.


The compound iloprost, a form of prostacyclin, is similar to a natural chemical in the body that widens blood vessels, such as those in the arteries or lungs. It is used to treat pulmonary arterial hypertension (high blood pressure in the pulmonary arteries).

Recent studies show that most patients with non-small cell lung cancer (NSCLC) have decreased levels of prostacyclin and demonstrate that prostacyclin supplementation with oral iloprost can prevent the development of lung cancer in mice exposed to cigarette smoke.

Based on the promising results of past research, a multi-centered, double-blind, placebo-controlled phase II trial of iloprost in subjects at increased risk for lung cancer was conducted. One-hundred fifty-two current or former smokers with an abnormal sputum cytology, at least a 20-year history of smoking a pack of cigarettes per day, and smoking-related damage in the central airways participated in fluorescent and white light bronchoscopies with biopsies taken at six different standard sites. Subjects were then randomized to receive oral iloprost or placebo for six months. A second bronchoscopy and repeat biopsies were completed at the end of the treatment period.

All biopsies were scored on a 1-8 scale based on World Health Organization (WHO) criteria. Histology measures were assessed according to the worst biopsy score, average biopsy score and dysplasia index. After conducting the follow-up bronchoscopies, former smokers who received iloprost showed significantly greater improvement in all the histology measures compared to those who received placebo. Iloprost did not have a significant effect on participants who continued to smoke throughout the trial.

"These promising findings show that oral iloprost has the potential to help prevent lung cancer and improve endobronchial dysplasia in former smokers," says Robert Keith, M.D., lead author and associate professor of medicine at the University of Colorado School of Medicine. "More research is needed to better understand the benefits of iloprost, but we are encouraged by these findings and believe iloprost should progress to a larger, phase III trial."

Dr. Keith will present this study on Tuesday, August, 4, 2009 at 1:30 pm PT in Moscone West, Room 2020-2022, Level 2.


Lung cancer kills more men and women than any other cancer. Although early detection has been shown to significantly increase the patient's chance of survival, screening for lung cancer is not routinely practiced. Chest X-ray and computed tomography (CT) have been proposed as screening tools; however, their two main drawbacks are the lack of discrimination between cancerous and benign lesionsmost lesions turn out to be harmless after needle biopsiesand the inability to detect pre-cancerous lesions.

It has been known for decades that sputum (phlegm) from lung cancer patients frequently contains cancer cells that can be microscopically detected. Cancer diagnoses based on human, slide-based review, is correct most often for normal cases. However, this method yields inconsistent results among cytologists and usually is associated with an unacceptable false negative rate.

The Lung Cell Evaluation Device (LuCED) is an automated 3D cell imaging platform, aimed at detection of pre-cancerous and cancerous cells in sputum. The technology was developed by researchers at VisionGate, Inc., in collaboration with scientists from the University of Washington. In this study, the investigators assessed a large number of normal cells and cancer cells. LuCED automatically produces 3D cell volumetric data, allowing for the measurement of 3D cellular features that correlate with abnormal conditions. The cell measurements are then translated into an analytical score that reflects the patient's cancer risk. LuCED, based on 3D cell analysis, produced near perfect discrimination between normal and cancer cell morphology.

"Based on abnormal cell prevalence counts in sputum from patients with cancer, we estimate that the LuCED test demonstrates near-perfect specificity (no false positives) while maintaining sensitivity that exceeds 90 percent for patients with lung cancer cells in their sputum," says Michael Meyer, M.S, lead author and vice president for image engineering at VisionGate. "This type of 3D analysis provides an unobstructed and unambiguous representation of normal and abnormal cell morphology, making the LuCED test an effective means to guide the physicians' further diagnostic workup, including diagnostic CT or bronchoscopy."

Mr. Meyer will present this study on Tuesday, August, 4, 2009 at 12:50 pm PT in Moscone West, Room 2020-2022, Level 2.


Lung cancer's status as the most common cause of cancer-related death worldwide is due in part to its difficulty to diagnose at an early stage. Symptoms often don't appear in patients until the cancer has spread beyond the lungs, thus making a novel test for early-stage lung cancer critical. Previous studies have examined the sputum, or respiratory fluid, of lung cancer patients to determine the differences when compared to the sputum of healthy individuals.

In this study, Erik Thunnissen, M.D., of Pathologisch Anatomisch Laboratorium in the Netherlands, and his team expand on previous research to evaluate the presence of chemical compounds called methyl groups in sputum, and their relationship to the presence of lung cancer. After selecting three genes for their methyl groups, the team examined a total of 570 sputum samples of both lung cancer and healthy patients.

Researchers found that when evaluating the samples with cytological examination at the microscope, a classification of "suspicious for carcinoma" or "malignant" yielded a 29.5 percent sensitivity rate, the ability of the test to predict the presence of lung cancer. If the RASSF1A gene alone was used for methyl group presence, the sensitivity of the test was 41 percent. The combination of both increases the sensitivity to 54 percent.

For a combination of the selected three genes for methyl groups, however, the sensitivity increased to 61 percent, supporting the use of methylation analysis in sputum as a way to potentially diagnose lung cancer.

"This test could offer a novel, non-invasive and accurate way to test for the presence of lung cancer, possibly improving the chances of an early diagnosis and a better prognosis," says Dr. Thunnissen.

Dr. Thunnissen will present this study on Tuesday, August, 4, 2009 at 1:20 pm PT in Moscone West, Room 2020-2022, Level 2.


Contact: Liz Wulderk
International Association for the Study of Lung Cancer

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