title: Multimodal lung cancer screening using the ITALUNG biomarker panel and low dose computed tomography. Results of the ITALUNG biomarker study.
abstract: Asymptomatic high-risk subjects, randomized in the intervention arm of the ITALUNG trial (1,406 screened for lung cancer), were enrolled for the ITALUNG biomarker study (n = 1,356), in which samples of blood and sputum were analyzed for plasma DNA quantification (cut off 5 ng/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%.
authors.affiliation: Regional Cancer Prevention Laboratory, ISPO-Cancer Prevention and Research Institute, Florence, Italy.
authors.forename: Francesca Maria
authors.initials: FM
authors.lastname: Carozzi
authors.affiliation: Regional Cancer Prevention Laboratory, ISPO-Cancer Prevention and Research Institute, Florence, Italy.
authors.forename: Simonetta
authors.initials: S
authors.lastname: Bisanzi
authors.affiliation: Cardiopulmonary Department, University Hospital of Pisa, Pisa, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Carrozzi
authors.affiliation: Radiology Department, University Hospital of Pisa, Pisa, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Falaschi
authors.affiliation: Retired, Pneumonology Department, Careggi Hospital, Florence, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Lopes Pegna
authors.affiliation: Radiodiagnostic Section, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Mascalchi
authors.affiliation: Radiodiagnostic Unit, ISPO-Cancer Prevention and Research Institute, Florence, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Picozzi
authors.affiliation: Regional Cancer Prevention Laboratory, ISPO-Cancer Prevention and Research Institute, Florence, Italy.
authors.forename: Marco
authors.identifier: 0000-0001-7646-7967
authors.initials: M
authors.lastname: Peluso
authors.affiliation: Regional Cancer Prevention Laboratory, ISPO-Cancer Prevention and Research Institute, Florence, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Sani
authors.affiliation: Biologist, formerly at ISPO-Cancer Prevention and Research Institute, Florence, Italy.
authors.forename: Luana
authors.initials: L
authors.lastname: Greco
authors.affiliation: Statistician, Florence, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Ocello
authors.affiliation: Retired, formerly at ISPO-Cancer Prevention and Research Institute, Florence, Italy.
authors.forename: Eugenio
authors.initials: E
authors.lastname: Paci
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D004273:DNA, Neoplasm / Q000097:blood; D055088:Early Detection of Cancer; D005260:Female; D006801:Humans; D007558:Italy; D019656:Loss of Heterozygosity / Q000235:genetics; D008168:Lung / Q000000981:diagnostic imaging / Q000473:pathology; D008175:Lung Neoplasms / Q000097:blood* / Q000000981:diagnostic imaging* / Q000235:genetics / Q000473:pathology; D008297:Male; D008403:Mass Screening; D053842:Microsatellite Instability; D008875:Middle Aged; D064847:Multimodal Imaging; D012907:Smoking; D013183:Sputum / Q000378:metabolism; D014057:Tomography, X-Ray Computed
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm
keywords: genomic instability; lung cancer screening; peripheral blood; plasma DNA; sputum