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CIRCULATING PLASMA DNA IS A DIAGNOSTIC MARKER FOR CENTRAL EARLY LUNG CANCER
October 2008, Vol 134, No. 4_MeetingAbstracts Abstract: Poster Presentations | October 2008
CIRCULATING PLASMA DNA IS A DIAGNOSTIC MARKER FOR CENTRAL EARLY LUNG CANCER Pyng Lee, MD*; Hes A. Brokx, MD; Clarissa Kooi, BSc; Remco M. van den Berg, MD; Tom G. Sutedja, PhD; Danielle A. Heideman, PhD Singapore General Hospital, Singapore, Singapore Chest Chest. 2008;134(4_MeetingAbstracts):p156003. doi:10.1378/chest.134.4_MeetingAbstracts.p156003
Abstract PURPOSE: Background: Elevated circulating plasma DNA (cpDNA) is detected in patients with lung cancer compared against cancer-free individuals. We hypothesized that cpDNA could serve as a diagnostic marker for the detection of roentgenographically occult lung cancer (ROLC) as well as a test for screening individuals at risk of lung cancer. METHODS: The amount of cpDNA was determined through real-time quantitative polymerase chain reaction (PCR) amplification of human fra-1 gene in: 14 patients with ROLC measuring ≤;1 cm2 using autofluorescence bronchoscopy, confined within the bronchial wall on high resolution computed tomography and fluorodeoxyglucose positron emission tomography negative; 4 patients with severe dysplasia or carcinoma in-situ; 10 patients with stage II-IV nonsmall cell carcinoma (NSCLC); and 10 cancer-free controls. Values were presented as median and inter-quartile range, and comparisons between groups were performed with Mann-Whitney U and Kruskal-Wallis tests. A p-value <0.05 was considered statistically significant. RESULTS: Median concentrations of cpDNA for ROLC and severe dysplasia/ carcinoma insitu were 2.63ng/αl(1.47–6.23) and 3.68ng/αl (2.38–5.09) respectively while they were 5.52ng/αl (1.61–12.17) and 1.72ng/αl (0.97–2.36) for patients with NSCLC and cancer-free controls. Patients with ROLC as well as severe dysplasia and carcinoma in-situ differed in cpDNA concentrations from cancer-free controls (p=0.014), however cpDNA was not discriminatory for ROLC over its precursors (p=0.72). CONCLUSION: Quantification of cpDNA is a useful non-invasive marker for early central airway cancers, and can be extended to screening individuals at risk. However, since it is not discriminatory for ROLC over severe dysplasia and carcinoma in-situ, it cannot be used recommended as a surrogate test for monitoring. CLINICAL IMPLICATIONS: Quantification of cpDNA, which requires a blood sample, can be applied as a non-invasive diagnostic marker for lung cancer. Its detection appears independent of tumor stage and is elevated in patients with ROLC (stage 0). It may herald promise as a screening test for individuals at risk.
DISCLOSURE: Pyng Lee, No Financial Disclosure Information; No Product/Research Disclosure Information Wednesday, October 29, 2008 1:00 PM - 2:15 PM
CIRCULATING PLASMA DNA IS A DIAGNOSTIC MARKER FOR CENTRAL EARLY LUNG CANCER Pyng Lee, MD*; Hes A. Brokx, MD; Clarissa Kooi, BSc; Remco M. van den Berg, MD; Tom G. Sutedja, PhD; Danielle A. Heideman, PhD Singapore General Hospital, Singapore, Singapore Chest Chest. 2008;134(4_MeetingAbstracts):p156003. doi:10.1378/chest.134.4_MeetingAbstracts.p156003
Abstract PURPOSE: Background: Elevated circulating plasma DNA (cpDNA) is detected in patients with lung cancer compared against cancer-free individuals. We hypothesized that cpDNA could serve as a diagnostic marker for the detection of roentgenographically occult lung cancer (ROLC) as well as a test for screening individuals at risk of lung cancer. METHODS: The amount of cpDNA was determined through real-time quantitative polymerase chain reaction (PCR) amplification of human fra-1 gene in: 14 patients with ROLC measuring ≤;1 cm2 using autofluorescence bronchoscopy, confined within the bronchial wall on high resolution computed tomography and fluorodeoxyglucose positron emission tomography negative; 4 patients with severe dysplasia or carcinoma in-situ; 10 patients with stage II-IV nonsmall cell carcinoma (NSCLC); and 10 cancer-free controls. Values were presented as median and inter-quartile range, and comparisons between groups were performed with Mann-Whitney U and Kruskal-Wallis tests. A p-value <0.05 was considered statistically significant. RESULTS: Median concentrations of cpDNA for ROLC and severe dysplasia/ carcinoma insitu were 2.63ng/αl(1.47–6.23) and 3.68ng/αl (2.38–5.09) respectively while they were 5.52ng/αl (1.61–12.17) and 1.72ng/αl (0.97–2.36) for patients with NSCLC and cancer-free controls. Patients with ROLC as well as severe dysplasia and carcinoma in-situ differed in cpDNA concentrations from cancer-free controls (p=0.014), however cpDNA was not discriminatory for ROLC over its precursors (p=0.72). CONCLUSION: Quantification of cpDNA is a useful non-invasive marker for early central airway cancers, and can be extended to screening individuals at risk. However, since it is not discriminatory for ROLC over severe dysplasia and carcinoma in-situ, it cannot be used recommended as a surrogate test for monitoring. CLINICAL IMPLICATIONS: Quantification of cpDNA, which requires a blood sample, can be applied as a non-invasive diagnostic marker for lung cancer. Its detection appears independent of tumor stage and is elevated in patients with ROLC (stage 0). It may herald promise as a screening test for individuals at risk.
DISCLOSURE: Pyng Lee, No Financial Disclosure Information; No Product/Research Disclosure Information Wednesday, October 29, 2008 1:00 PM - 2:15 PM