Asymptomatic high-risk subjects, randomized in the intervention arm of the ITALUNG trial (1406 screened
for lung cancer), were enrolled for the ITALUNG biomarker study (n = 1356), in which samples of blood
and sputum were analysed for plasma DNA quantification (cut off 5ng/ml), loss of heterozygosity and
microsatellite instability. The ITALUNG biomarker panel (IBP) was considered positive if at least one of the
two biomarkers included in the panel was positive. Subjects with and without lung cancer diagnosis at the
end of the screening cycle with LDCT (n = 517) were evaluated. Out of 18 baseline screen detected lung
cancer cases, 17 were IBP positive (94%). Repeat screen-detected lung cancer cases were 18 and 12 of them
positive at baseline IBP test (66%). Interval cancer cases (2-years) and biomarker tests after a suspect Non
Calcific Nodule follow-up were investigated. The single test versus multimodal screening measures of
accuracy were compared in a simulation within the screened ITALUNG intervention arm, considering
screen-detected and interval cancer cases. Sensitivity was 90% at baseline screening. Specificity was 71%%
and 61% for LDCT and IBP as baseline single test, and improved at 89% with multimodal, combined
screening. The positive predictive value was 4.3% for LDCT at baseline and 10.6% for multimodal
screening. Multimodal screening could improve the screening efficiency at baseline and strategies for future
implementation are discussed. If IBP was used as primary screening test, the LDCT burden might decrease
of about 60%