Encouraging results in lung cancer mortality reduction were obtained by the introduction of low dose computed tomography (LDCT) screening. The results of Nelson screening trial showed the benefit of LC screening with LDCT, with a 26% reduction in lung cancer mortality in the LDCT arm. Nonetheless, the development of non-invasive complementary biomarkers could be helpful to improve the efficacy of LDCT screening.
Among blood based biomarkers, autoantibodies (AAbs) resulted in high specificity (over 90%) but low sensitivity (around 40%). Similar results were obtained analyzing C4d plasma levels. Serum DNA methylation, recently resulted in 93% sensitivity and 62% specificity in discriminating subjects with suspicious nodules. Circulating tumor DNA (ctDNA) reported a 48% sensitivity for early stage lung cancer detection. When combined with a panel of blood proteins, its sensitivity increased to 59%. Preliminary results of the Circulating Cell-free Genome Atlas (CCGA) study revealed a sensitivity of 48% for targeted NGS, 54% for whole genome sequencing, and 56% for methylome profiling with a fixed 95% specificity in stage I-III lung cancer cases.
In order to implement lung cancer screening programs, we initially focused on circulating free DNA (cfDNA) and then moved to circulating microRNA (miRNA). A plasma miRNA signature classifier (MSC) showed high performance in terms of sensitivity (87%) and specificity (81%) in subjects enrolled LDCT screening trials. These results prompted us to launch in 2013 a prospective study, called bioMILD, to test the efficiency of a combined LDCT-MSC approach as screening tests in a large cohort of 4000 smokers, 50 yrs or older. Results will be expected for half 2019.