{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T17:09:18Z","timestamp":1790096958540,"version":"4.0.1"},"reference-count":47,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T00:00:00Z","timestamp":1789862400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"local government of Tuscany","award":["1014 of 02.25.2004"],"award-info":[{"award-number":["1014 of 02.25.2004"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>The ITALUNG trial (Italian Lung Cancer Screening Trial) is a randomised controlled trial that evaluated the efficacy of Low-Dose Computed Tomography (LDCT) for lung cancer screening of over 3100 high-risk individuals, smokers and ex-smokers, aged 55\u201369. ITALUNG was coordinated by the Institute for Cancer Prevention Research in Florence and carried out across Tuscany in three main screening centres: Florence, Pisa, and Pistoia. The ITALUNG study demonstrated lower long-term lung cancer (LC) and cardiovascular mortality in the screened groups, with notable benefits observed in women. When the performance of the ITALUNG biomarker panel, i.e., loss of heterozygosity and microsatellite instability (LOH\/MSI) and circulating free DNA (cfDNA), was analysed in samples of blood and sputum from asymptomatic high-risk subjects screened for lung cancer, sensitivity (SE) was 90% at baseline screening. However, the respective roles of LDCT screening and fluid biomarkers in screening for lung cancer are not established, highlighting the need for biomarkers to be able to detect tumours not only at the time of diagnosis but also when tested in pre-diagnostic samples. Therefore, we evaluated the longitudinal changes in the performance of multiple biomarkers in the ITALUNG biomarker panel and\/or its single components to identify LC patients in ITALUNG. The cohort consisted of 55 LC patients whose biological specimens were collected over several years before diagnosis. Good results were found in test specimens obtained close to the time of diagnosis; out of 21 LC cases, 20 were positive in the ITALUNG biomarker panel [95% SE; 95% C.I. 0.86\u20131.04], 18 for LOH\/MSI (86% SE; 95% C.I. 0.71\u20131.01) and 17 for cfDNA (85% SE; 95% C.I. 0.70\u20131.00). The panel was able to identify over 80% of LC cases by analysing the pre-diagnostic samples collected within 3 years prior to diagnosis: out of six LC patients, five were positive in the ITALUNG biomarker panel (83% SE; 95% C.I. 0.53\u20131.13). In addition, over 67% of the early and resected cancer cases were detected by the multiple-biomarker panel when biomarker testing samples were obtained within 11 years prior to diagnosis. The positivity of the ITALUNG biomarker panel might be associated with both carcinogenic field effects and early tumour presence when using pre-diagnostic samples obtained several years before diagnosis.<\/jats:p>","DOI":"10.3390\/ijms27188376","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T13:32:12Z","timestamp":1790083932000},"page":"8376","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Biomarker Detection of Lung Cancers Before Clinical Symptoms or the Use of Traditional Imaging Methods in the ITALUNG Trial"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8119-9119","authenticated-orcid":false,"given":"Simonetta","family":"Bisanzi","sequence":"first","affiliation":[{"name":"Regional Laboratory of Cancer Prevention, Institute for Cancer Research, Prevention and Clinical Network (ISPRO), 50139 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5826-2455","authenticated-orcid":false,"given":"Valentina","family":"Russo","sequence":"additional","affiliation":[{"name":"Regional Laboratory of Cancer Prevention, Institute for Cancer Research, Prevention and Clinical Network (ISPRO), 50139 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Carrozzi","sequence":"additional","affiliation":[{"name":"Pulmonary Unit, Cardiothoracic and Vascular Department, University Hospital of Pisa, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8955-8913","authenticated-orcid":false,"given":"Cristina","family":"Sani","sequence":"additional","affiliation":[{"name":"Regional Laboratory of Cancer Prevention, Institute for Cancer Research, Prevention and Clinical Network (ISPRO), 50139 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Picozzi","sequence":"additional","affiliation":[{"name":"Clinical Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network (ISPRO), 50139 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Utili","sequence":"additional","affiliation":[{"name":"Regional Laboratory of Cancer Prevention, Institute for Cancer Research, Prevention and Clinical Network (ISPRO), 50139 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5537-2982","authenticated-orcid":false,"given":"Mario","family":"Mascalchi","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Biomedical Sciences \u201cMario Serio\u201d, University of Florence, 50121 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca Maria","family":"Carozzi","sequence":"additional","affiliation":[{"name":"Regional Laboratory of Cancer Prevention, Institute for Cancer Research, Prevention and Clinical Network (ISPRO), 50139 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9648-3902","authenticated-orcid":false,"given":"Eugenio","family":"Paci","sequence":"additional","affiliation":[{"name":"Clinical Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network (ISPRO), 50139 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7646-7967","authenticated-orcid":false,"given":"Marco","family":"Peluso","sequence":"additional","affiliation":[{"name":"Regional Laboratory of Cancer Prevention, Institute for Cancer Research, Prevention and Clinical Network (ISPRO), 50139 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the ITALUNG Working Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,20]]},"reference":[{"key":"ref_1","first-page":"e70043","article-title":"Cancer statistics, 2026","volume":"76","author":"Siegel","year":"2026","journal-title":"CA Cancer J. 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