Published ahead of print on September 11, 2008, doi:10.1164/rccm.200807-1068OC
© 2009 American Thoracic Society doi: 10.1164/rccm.200807-1068OC
Plasma DNA Quantification in Lung Cancer Computed Tomography ScreeningFive-Year Results of a Prospective Study1 Department of Experimental Oncology, Molecular Cytogenetics Unit, 2 Unit of Medical Statistics and Biometry, and 3 Unit of Thoracic Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy Correspondence and requests for reprints should be addressed to Gabriella Sozzi, Ph.D., Department of Experimental Oncology, Molecular Cytogenetics Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, via G. Venezian 1, 20133, Milan, Italy. E-mail: gabriella.sozzi{at}istitutotumori.mi.it Rationale: Free circulating plasma DNA has emerged as a potential biomarker for early lung cancer detection. In a previous case–control study we have shown that high levels of plasma DNA are a strong risk factor for lung cancer. Objectives: To assess the diagnostic performance and prognostic value of plasma DNA levels in a cohort of 1,035 heavy smokers monitored by annual spiral computed tomography (CT) for 5 years. Methods: Plasma DNA levels were determined through real-time quantitative PCR at baseline and at time of lung cancer diagnosis. Screening performance of the assay was calculated through the area under the receiver-operating characteristic curve (AUC-ROC). Kaplan-Meier analyses were computed for association with prognosis. Measurements and Main Results: Median baseline concentration of plasma DNA was not different in individuals who developed CT-detected lung cancers in the 5-year period (n = 38) versus cancer-free control subjects (AUC-ROC, 0.496; P = 0.9330), and only slightly higher at the time of cancer diagnosis (AUC-ROC, 0.607; P = 0.0369). At surgery, plasma DNA was higher in tumors detected at baseline (AUC-ROC, 0.80; P < 0.0001) and in Stage II to IV tumors detected during the first 2 years of screening (AUC-ROC, 0.87; P < 0.0001). A longitudinal study of plasma DNA levels showed increased values approaching to lung cancer diagnosis (P = 0.0010). Higher plasma DNA was significantly associated with poorer 5-year survival (P = 0.0066). Conclusions: Baseline assessment of plasma DNA level does not improve the accuracy of lung cancer screening by spiral CT in heavy smokers. Higher levels of plasma DNA at surgery might represent a risk factor for aggressive disease.
Key Words: lung cancer • circulating DNA • spiral computed tomography
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