Early Detection of Lung Cancer Based on the Presence of Lung-derived cfDNA in Plasma- Preliminary Results

<bold>Introduction:</bold> Methylation patterns identify the tissue origins of circulating cell-free DNA (cfDNA). The levels are correlated with tissue-specific pathology. We previously demonstrated elevated concentrations of lung-derived cfDNA among patients with lung cancer and other lung pathologies. This study aimed to evaluate the possibility that lung-derived cfDNA might play a role in early detection lung cancer. <bold>Methods:</bold> We recruited heavy smokers and ex-smokers (20 pack years and more) aged 50 or more who were referred to low-dose chest computed tomography (LDCT) for early detection. The participants performed spirometry. Respiratory symptoms were assessed by questionnaire. A blood sample for cfDNA was drawn from all participants. The levels of cfDNA were assessed. Statistical analysis evaluated the sensitivity and specificity of the test to detect lung cancer. <bold>Results:</bold> Ninety-three participants who performed LDCT were included. 62 males and 31 females. Average age 62+7.9. 4 were diagnosed as suffering from lung cancer according to LDCT and biopsy. The levels of cfDNA originating from the lungs were higher among participants with lung cancer (23.35 copies per ml) as compared to participants without lung cancer (1.21 copies per ml). P=0.087. Sensitivity-0.75. Specificity-0.9 and area under the curve (AUC) = 0.74. The results showed a trend of higher levels of cfDNA among participants with lung cancer but it did not reach statistical significance <bold>Conclusions:</bold> The results showed a trend of higher levels of lung-derived cfDNA among patients diagnosed as suffering from lung cancer in a screening program compared to participants without cancer. A larger study is needed to prove the concept