Multimodal lung cancer screening using the ITALUNG Biomarker Panel and Low Dose Computed Tomography. Results of the ITALUNG biomarker study.

Carozzi FM1, Bisanzi S1, Carrozzi L2, Falaschi F3, Lopes Pegna A4, Mascalchi M5, Picozzi G6, Peluso M1, Sani C1, Greco L7, Ocello C8, Paci E9; and the ITALUNG Working Group.

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Abstract

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%. This article is protected by copyright. All rights reserved.