{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T15:46:17Z","timestamp":1783957577222,"version":"3.55.0"},"reference-count":97,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2024,1,18]],"date-time":"2024-01-18T00:00:00Z","timestamp":1705536000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health, Finalizzata Ministeriale 2016","award":["PE-2016-02364336"],"award-info":[{"award-number":["PE-2016-02364336"]}]},{"name":"Italian Ministry of Health, Finalizzata Ministeriale 2016","award":["TRANSCAN-045"],"award-info":[{"award-number":["TRANSCAN-045"]}]},{"name":"Italian Ministry of Health, Finalizzata Ministeriale 2016","award":["20486"],"award-info":[{"award-number":["20486"]}]},{"name":"TRANSCAN-2 Joint Transnational Call 2016","award":["PE-2016-02364336"],"award-info":[{"award-number":["PE-2016-02364336"]}]},{"name":"TRANSCAN-2 Joint Transnational Call 2016","award":["TRANSCAN-045"],"award-info":[{"award-number":["TRANSCAN-045"]}]},{"name":"TRANSCAN-2 Joint Transnational Call 2016","award":["20486"],"award-info":[{"award-number":["20486"]}]},{"name":"Italian Association for Cancer Research (AIRC)","award":["PE-2016-02364336"],"award-info":[{"award-number":["PE-2016-02364336"]}]},{"name":"Italian Association for Cancer Research (AIRC)","award":["TRANSCAN-045"],"award-info":[{"award-number":["TRANSCAN-045"]}]},{"name":"Italian Association for Cancer Research (AIRC)","award":["20486"],"award-info":[{"award-number":["20486"]}]},{"name":"NPO \u2018Fondazione Umberto Veronesi ETS\u2019","award":["PE-2016-02364336"],"award-info":[{"award-number":["PE-2016-02364336"]}]},{"name":"NPO \u2018Fondazione Umberto Veronesi ETS\u2019","award":["TRANSCAN-045"],"award-info":[{"award-number":["TRANSCAN-045"]}]},{"name":"NPO \u2018Fondazione Umberto Veronesi ETS\u2019","award":["20486"],"award-info":[{"award-number":["20486"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Lung cancer screening with low-dose helical computed tomography (LDCT) reduces mortality in high-risk subjects. Cigarette smoking is linked to up to 90% of lung cancer deaths. Even more so, it is a key risk factor for many other cancers and cardiovascular and pulmonary diseases. The Smokers health Multiple ACtions (SMAC-1) trial aimed to demonstrate the feasibility and effectiveness of an integrated program based on the early detection of smoking-related thoraco-cardiovascular diseases in high-risk subjects, combined with primary prevention. A new multi-component screening design was utilized to strengthen the framework on conventional lung cancer screening programs. We report here the study design and the results from our baseline round, focusing on oncological findings. Methods: High-risk subjects were defined as being &gt;55 years of age and active smokers or formers who had quit within 15 years (&gt;30 pack\/y). A PLCOm2012 threshold &gt;2% was chosen. Subject outreach was streamlined through media campaign and general practitioners\u2019 engagement. Eligible subjects, upon written informed consent, underwent a psychology consultation, blood sample collection, self-evaluation questionnaire, spirometry, and LDCT scan. Blood samples were analyzed for pentraxin-3 protein levels, interleukins, microRNA, and circulating tumor cells. Cardiovascular risk assessment and coronary artery calcium (CAC) scoring were performed. Direct and indirect costs were analyzed focusing on the incremental cost-effectiveness ratio per quality-adjusted life years gained in different scenarios. Personalized screening time-intervals were determined using the \u201cMaisonneuve risk re-calculation model\u201d, and a threshold &lt;0.6% was chosen for the biennial round. Results: In total, 3228 subjects were willing to be enrolled. Out of 1654 eligible subjects, 1112 participated. The mean age was 64 years (M\/F 62\/38%), with a mean PLCOm2012 of 5.6%. Former and active smokers represented 23% and 77% of the subjects, respectively. At least one nodule was identified in 348 subjects. LDCTs showed no clinically significant findings in 762 subjects (69%); thus, they were referred for annual\/biennial LDCTs based on the Maisonneuve risk (mean value = 0.44%). Lung nodule active surveillance was indicated for 122 subjects (11%). Forty-four subjects with baseline suspicious nodules underwent a PET-FDG and twenty-seven a CT-guided lung biopsy. Finally, a total of 32 cancers were diagnosed, of which 30 were lung cancers (2.7%) and 2 were extrapulmonary cancers (malignant pleural mesothelioma and thymoma). Finally, 25 subjects underwent lung surgery (2.25%). Importantly, there were zero false positives and two false negatives with CT-guided biopsy, of which the patients were operated on with no stage shift. The final pathology included lung adenocarcinomas (69%), squamous cell carcinomas (10%), and others (21%). Pathological staging showed 14 stage I (47%) and 16 stage II-IV (53%) cancers. Conclusions: LDCTs continue to confirm their efficacy in safely detecting early-stage lung cancer in high-risk subjects, with a negligible risk of false-positive results. Re-calculating the risk of developing lung cancer after baseline LDCTs with the Maisonneuve model allows us to optimize time intervals to subsequent screening. The Smokers health Multiple ACtions (SMAC-1) trial offers solid support for policy assessments by policymakers. We trust that this will help in developing guidelines for the large-scale implementation of lung cancer screening, paving the way for better outcomes for lung cancer patients.<\/jats:p>","DOI":"10.3390\/cancers16020417","type":"journal-article","created":{"date-parts":[[2024,1,18]],"date-time":"2024-01-18T11:28:46Z","timestamp":1705577326000},"page":"417","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The Smokers Health Multiple ACtions (SMAC-1) Trial: Study Design and Results of the Baseline Round"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0308-3054","authenticated-orcid":false,"given":"Alberto","family":"Antonicelli","sequence":"first","affiliation":[{"name":"Faculty of Medicine and Surgery, School of Thoracic Surgery, Universit\u00e0 Vita-Salute San Raffaele, 20132 Milan, Italy"},{"name":"Department of Thoracic Surgery, IRCCS Ospedale San Raffaele, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1341-1071","authenticated-orcid":false,"given":"Piergiorgio","family":"Muriana","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, IRCCS Ospedale San Raffaele, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Favaro","sequence":"additional","affiliation":[{"name":"Department of Anesthesia and Intensive Care, IRCCS Istituto Oncologico Veneto (IOV), 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8394-2719","authenticated-orcid":false,"given":"Giuseppe","family":"Mangiameli","sequence":"additional","affiliation":[{"name":"Division of Thoracic Surgery, IRCCS Humanitas Research Hospital, 20089 Rozzano, Italy"},{"name":"Department of Biomedical Sciences, Humanitas University, 20072 Pieve Emanuele, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1889-8798","authenticated-orcid":false,"given":"Ezio","family":"Lanza","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Humanitas University, 20072 Pieve Emanuele, Italy"},{"name":"Department of Interventional Radiology, IRCCS Humanitas Clinical and Research Center, 20089 Rozzano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Profili","sequence":"additional","affiliation":[{"name":"Department of Interventional Radiology, IRCCS Humanitas Clinical and Research Center, 20089 Rozzano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7412-8638","authenticated-orcid":false,"given":"Fabrizio","family":"Bianchi","sequence":"additional","affiliation":[{"name":"Unit of Cancer Biomarkers, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuela","family":"Fina","sequence":"additional","affiliation":[{"name":"Division of Thoracic Surgery, IRCCS Humanitas Research Hospital, 20089 Rozzano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Ferrante","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Humanitas University, 20072 Pieve Emanuele, Italy"},{"name":"Cardio Center, IRCCS Humanitas Research Hospital, 20089 Rozzano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Ghislandi","sequence":"additional","affiliation":[{"name":"CERGAS and Department of Social and Political Sciences, Bocconi University, 20136 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7665-3783","authenticated-orcid":false,"given":"Daniela","family":"Pistillo","sequence":"additional","affiliation":[{"name":"Center for Biological Resources, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, 20089 Rozzano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna","family":"Finocchiaro","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, 20089 Rozzano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluigi","family":"Condorelli","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Humanitas University, 20072 Pieve Emanuele, Italy"},{"name":"Cardio Center, IRCCS Humanitas Research Hospital, 20089 Rozzano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3944-2490","authenticated-orcid":false,"given":"Rosalba","family":"Lembo","sequence":"additional","affiliation":[{"name":"Department of Anesthesia and Intensive Care, Section of Biostatistics, Universit\u00e0 Vita-Salute San Raffaele, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6087-3901","authenticated-orcid":false,"given":"Pierluigi","family":"Novellis","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, IRCCS Ospedale San Raffaele, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Dieci","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, IRCCS Ospedale San Raffaele, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"De Santis","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, IRCCS Ospedale San Raffaele, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Veronesi","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Surgery, School of Thoracic Surgery, Universit\u00e0 Vita-Salute San Raffaele, 20132 Milan, Italy"},{"name":"Department of Thoracic Surgery, IRCCS Ospedale San Raffaele, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"E359","DOI":"10.1002\/ijc.29210","article-title":"Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012","volume":"136","author":"Ferlay","year":"2015","journal-title":"Int. J. Cancer"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1148\/radiol.2018180212","article-title":"Barriers to Lung Cancer Screening Engagement from the Patient and Provider Perspective","volume":"290","author":"Wang","year":"2019","journal-title":"Radiology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1016\/j.lungcan.2008.01.001","article-title":"Lung cancer screening with low-dose computed tomography: A non-invasive diagnostic protocol for baseline lung nodules","volume":"61","author":"Veronesi","year":"2008","journal-title":"Lung Cancer"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"National Lung Screening Trial Research Team, Aberle, D.R., Adams, A.M., Berg, C.D., Black, W.C., Clapp, J.D., Fagerstrom, R.M., Gareen, I.F., Gatsonis, C., and Marcus, P.M. (2011). Reduced lung-cancer mortality with low-dose computed tomographic screening. N. Engl. J. Med., 365, 395\u2013409.","DOI":"10.1056\/NEJMoa1102873"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.lungcan.2010.10.025","article-title":"Assessment of lung-cancer mortality reduction from CT Screening","volume":"71","author":"Henschke","year":"2011","journal-title":"Lung Cancer"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1097\/JTO.0b013e31824fe942","article-title":"Lung cancer screening and video-assisted thoracic surgery","volume":"7","author":"Petersen","year":"2012","journal-title":"J. Thorac. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/j.thorsurg.2023.04.017","article-title":"Lung Cancer Screening: The European Perspective","volume":"33","author":"Muriana","year":"2023","journal-title":"Thorac. Surg. Clin."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1097\/JTO.0b013e3181a0d98f","article-title":"The Danish randomized lung cancer CT screening trial\u2014Overall design and results of the prevalence round","volume":"4","author":"Pedersen","year":"2009","journal-title":"J. Thorac. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1097\/JTO.0b013e31823c58ab","article-title":"International Association for the Study of Lung Cancer Computed Tomography Screening Workshop 2011 report","volume":"7","author":"Field","year":"2012","journal-title":"J. Thorac. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1164\/rccm.201505-1040OC","article-title":"Results of the Randomized Danish Lung Cancer Screening Trial with Focus on High-Risk Profiling","volume":"193","author":"Wille","year":"2016","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1778","DOI":"10.1158\/1940-6207.CAPR-11-0026","article-title":"Lung cancer risk prediction to select smokers for screening CT\u2014A model based on the Italian COSMOS trial","volume":"4","author":"Maisonneuve","year":"2011","journal-title":"Cancer Prev. Res."},{"key":"ref_13","first-page":"411","article-title":"Recommendations from the European Society of Thoracic Surgeons (ESTS) regarding computed tomography screening for lung cancer in Europe","volume":"51","author":"Pedersen","year":"2017","journal-title":"Eur. J. Cardiothorac. Surg."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2300128","DOI":"10.1183\/13993003.00128-2023","article-title":"Developing a Pan-European Technical Standard for a Comprehensive High-quality Lung Cancer CT Screening Program. an ERS Technical Standard","volume":"61","author":"Baldwin","year":"2023","journal-title":"Eur. Respir. J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"411","DOI":"10.7326\/0003-4819-159-6-201309170-00690","article-title":"Screening for lung cancer with low-dose computed tomography: A systematic review to update the US Preventive services task force recommendation","volume":"159","author":"Humphrey","year":"2013","journal-title":"Ann. Intern. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1016\/j.jcmg.2015.02.006","article-title":"Coronary artery calcium scanning: Past, present, and future","volume":"8","author":"Hecht","year":"2015","journal-title":"JACC Cardiovasc. Imaging"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"159","DOI":"10.3109\/14017431.2015.1039572","article-title":"Coronary artery calcification detected in lung cancer screening predicts cardiovascular death","volume":"49","author":"Rasmussen","year":"2015","journal-title":"Scand. Cardiovasc. J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"ehac544.1269","DOI":"10.1093\/eurheartj\/ehac544.1269","article-title":"Ordinal scoring of coronary artery calcification in low dose computed tomography is predictive factor of all-cause death and cardiovascular events","volume":"43","author":"Kasprzyk","year":"2022","journal-title":"Eur. Heart J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"24","DOI":"10.31373\/ejtcm\/153487","article-title":"Comorbidities and clinical outcomes of a lung cancer screening trial participants with chronic obstructive pulmonary disease in three-year follow-up","volume":"5","author":"Undrunas","year":"2022","journal-title":"Eur. J. Transl. Clin. Med."},{"key":"ref_20","unstructured":"Pagliaro, B., Rossi, A., Favaro, G., Bruschini, P., Profili, M., Fina, E., Apollo, A., Spina, S., Retegno, I., and Patrinoiu, R. (2019). Humanitas Research Day, Humanitas University. Poster presentation."},{"key":"ref_21","unstructured":"Ferrante, G., Rossi, A., Favaro, G., Bruschini, P., Pagliaro, B., Fazzari, F., Profili, M., Lanza, E., Patrinoiu, R., and Pascucci, M.G. (2019). Humanitas Research Day, Humanitas University. Poster presentation."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.acra.2017.07.010","article-title":"Coronary Artery Calcium Imaging in the ROBINSCA Trial: Rationale, Design, and Technical Background","volume":"25","author":"Vonder","year":"2018","journal-title":"Acad. Radiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"081915","DOI":"10.1118\/1.4813904","article-title":"Can nontriggered thoracic CT be used for coronary artery calcium scoring? A phantom study","volume":"40","author":"Xie","year":"2013","journal-title":"Med. Phys."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.clinimag.2021.03.012","article-title":"The importance of low-dose CT screening to identify emphysema in asymptomatic participants with and without a prior diagnosis of COPD","volume":"78","author":"Steiger","year":"2021","journal-title":"Clin. Imaging"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"S218","DOI":"10.1016\/j.jtho.2023.09.354","article-title":"P1.15-02 Cardiovascular implications of Lung Cancer Screening Program: The Smokers health Multiple Actions (SMAC) Study","volume":"18","author":"Ferrante","year":"2023","journal-title":"J. Thorac. Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1097\/RTI.0000000000000136","article-title":"Computed tomography screening for lung cancer in the National Lung Screening Trial: A cost-effectiveness analysis","volume":"30","author":"Black","year":"2015","journal-title":"J. Thorac. Imaging"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.lungcan.2020.03.015","article-title":"Favorable incremental cost-effectiveness ratio for lung cancer screening in Italy","volume":"143","author":"Veronesi","year":"2020","journal-title":"Lung Cancer"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1097\/JTO.0000000000000283","article-title":"Pan-Canadian Early Detection of Lung Cancer Study Team. Resource utilization and costs during the initial years of lung cancer screening with computed tomography in Canada","volume":"9","author":"Cressman","year":"2014","journal-title":"J. Thorac. Oncol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1097\/JTO.0000000000000200","article-title":"Diagnostic performance of low-dose computed tomography screening for lung cancer over five years","volume":"9","author":"Veronesi","year":"2014","journal-title":"J. Thorac. Oncol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1016\/j.rmed.2015.05.009","article-title":"COPD prevalence in a north-eastern Italian general population","volume":"109","author":"Guerriero","year":"2015","journal-title":"Respir. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1136\/heartjnl-2013-305402","article-title":"MicroRNAs in cardiovascular disease: An introduction for clinicians","volume":"101","author":"Romaine","year":"2015","journal-title":"Heart"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"djv063","DOI":"10.1093\/jnci\/djv063","article-title":"miR-Test: A blood test for lung cancer early detection","volume":"107","author":"Montani","year":"2015","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Ilie, M., Hofman, V., Long-Mira, E., Selva, E., Vignaud, J.-M., Padovani, B., Mouroux, J., Marquette, C.-H., and Hofman, P. (2014). \u201cSentinel\u201d circulating tumor cells allow early diagnosis of lung cancer in patients with chronic obstructive pulmonary disease. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0111597"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1002\/ijc.29822","article-title":"Prognostic and diagnostic potential of local and circulating levels of pentraxin 3 in lung cancer patients","volume":"138","author":"Infante","year":"2016","journal-title":"Int. J. Cancer"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2177","DOI":"10.1016\/j.jacc.2014.01.050","article-title":"microRNAs in cardiovascular diseases: Current knowledge and the road ahead","volume":"63","author":"Condorelli","year":"2014","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1097\/AIA.0b013e318034194e","article-title":"Cytokines, inflammation, and pain","volume":"45","author":"Zhang","year":"2007","journal-title":"Int. Anesthesiol. Clin."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e2100378","DOI":"10.1200\/PO.21.00378","article-title":"Circulating Tumor-Macrophage Fusion Cells and Circulating Tumor Cells Complement Non-Small-Cell Lung Cancer Screening in Patients with Suspicious Lung-RADS 4 Nodules","volume":"6","author":"Manjunath","year":"2022","journal-title":"JCO Precis. Oncol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1002\/emmm.201100154","article-title":"A serum circulating miRNA diagnostic test to identify asymptomatic high-risk individuals with early stage lung cancer","volume":"3","author":"Bianchi","year":"2011","journal-title":"EMBO Mol. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1056\/NEJMoa1211776","article-title":"Selection criteria for lung-cancer screening","volume":"368","author":"Katki","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_40","unstructured":"(2023, September 12). Tumore del Polmone e Screening: In Humanitas Riuniti i Massimi Esperti Europei al Clearly Meeting\u2014Humanitas. Available online: https:\/\/www.humanitas.it\/news\/tumore-del-polmone-screening-humanitas-riuniti-massimi-esperti-europei-al-clearly-meeting\/."},{"key":"ref_41","unstructured":"Marino, L. (2024, January 14). La Disassuefazione dal Fumo: L\u2019ambulatorio. In Nardini, s.; Donner, C.; editors. L\u2019epidemia di fumo in Italia. Pisa: EDI-AIPO Scientifica; 2000\u2014Google Scholar. Available online: https:\/\/scholar.google.com\/scholar_lookup?title=La%20disassuefazione%20dal%20fumo%3A%20lambulatorio.%20Lepidemia%20di%20fumo%20in%20Italia&publication_year=2000&author=L.%20Marino."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1016\/j.jtho.2022.07.007","article-title":"Cytisine Therapy Improved Smoking Cessation in the Randomized Screening and Multiple Intervention on Lung Epidemics Lung Cancer Screening Trial","volume":"17","author":"Pastorino","year":"2022","journal-title":"J. Thorac. Oncol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"iv1","DOI":"10.1093\/annonc\/mdx222","article-title":"Early and locally advanced non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up","volume":"28","author":"Postmus","year":"2017","journal-title":"Ann. Oncol."},{"key":"ref_44","unstructured":"(2023, November 09). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines\u00ae) Non-Small Cell Lung Cancer 5.2023. Published 2023. Available online: https:\/\/www.nccn.org\/guidelines\/guidelines-detail?category=1&id=1450."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"S102","DOI":"10.1016\/j.jtho.2022.07.169","article-title":"P1.04-03 Independent Validation of the Maisonneuve Lung Cancer Risk Model to Optimize Screening Interval in High-risk Individuals","volume":"17","author":"Maisonneuve","year":"2022","journal-title":"J. Thorac. Oncol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Dama, E., Melocchi, V., Mazzarelli, F., Colangelo, T., Cuttano, R., Di Candia, L., Ferretti, G.M., Taurchini, M., Graziano, P., and Bianchi, F. (2020). Non-Coding RNAs as Prognostic Biomarkers: A miRNA Signature Specific for Aggressive Early-Stage Lung Adenocarcinomas. Non-Coding RNA, 6.","DOI":"10.3390\/ncrna6040048"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.ebiom.2016.02.038","article-title":"Circulating Cancer Biomarkers: The Macro-revolution of the Micro-RNA","volume":"5","author":"Montani","year":"2016","journal-title":"EBioMedicine"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Dama, E., Colangelo, T., Fina, E., Cremonesi, M., Kallikourdis, M., Veronesi, G., and Bianchi, F. (2021). Biomarkers and Lung Cancer Early Detection: State of the Art. Cancers, 13.","DOI":"10.3390\/cancers13153919"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.1016\/j.ebiom.2015.08.032","article-title":"Lung Cancer Early Detection: The Role of Circulating MicroRNAs","volume":"2","author":"Bianchi","year":"2015","journal-title":"EBioMedicine"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.lungcan.2018.07.036","article-title":"Cost-utility analysis of a potential lung cancer screening program for a high-risk population in Germany: A modelling approach","volume":"124","author":"Hofer","year":"2018","journal-title":"Lung Cancer"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1136\/thoraxjnl-2016-209825","article-title":"The ITALUNG Working Group. Mortality, survival and incidence rates in the ITALUNG randomised lung cancer screening trial","volume":"72","author":"Paci","year":"2017","journal-title":"Thorax."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1097\/JTO.0b013e31828f68d6","article-title":"ITALUNG Study Research Group. Four-year results of low-dose CT screening and nodule management in the ITALUNG trial","volume":"8","author":"Picozzi","year":"2013","journal-title":"J. Thorac. Oncol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1148\/radiol.2017162894","article-title":"Recommendations for Measuring Pulmonary Nodules at CT: A Statement from the Fleischner Society","volume":"285","author":"Bankier","year":"2017","journal-title":"Radiology"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"103","DOI":"10.4143\/crt.2022.264","article-title":"Korean Association for Lung Cancer; Korea Central Cancer Registry. Five-Year Overall Survival and Prognostic Factors in Patients with Lung Cancer: Results from the Korean Association of Lung Cancer Registry (KALC-R) 2015","volume":"55","author":"Jeon","year":"2023","journal-title":"Cancer Res. Treat."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.21037\/tlcr-22-240","article-title":"Survival of 7, 311 lung cancer patients by pathological stage and histological classification: A multicenter hospital-based study in China","volume":"11","author":"He","year":"2022","journal-title":"Transl. Lung Cancer Res."},{"key":"ref_56","unstructured":"(2023, September 21). Lung and Bronchus Cancer\u2014Cancer Stat Facts, Available online: https:\/\/seer.cancer.gov\/statfacts\/html\/lungb.html."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1016\/S1470-2045(19)30329-8","article-title":"5-year overall survival in patients with lung cancer eligible or ineligible for screening according to US Preventive Services Task Force criteria: A prospective, observational cohort study","volume":"20","author":"Luo","year":"2019","journal-title":"Lancet Oncol."},{"key":"ref_58","unstructured":"(2023, September 21). Lung Cancer Screening|Cancer Trends Progress Report, Available online: https:\/\/progressreport.cancer.gov\/detection\/lung_cancer."},{"key":"ref_59","unstructured":"(2023, September 12). Five Major Steps to Intervention (The \u201c5 A\u2019s\u201d)|Agency for Healthcare Research and Quality, Available online: https:\/\/www.ahrq.gov\/prevention\/guidelines\/tobacco\/5steps.html."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1136\/thoraxjnl-2017-211377","article-title":"Implementing lung cancer screening: Baseline results from a community-based \u2018Lung Health Check\u2019 pilot in deprived areas of Manchester","volume":"74","author":"Crosbie","year":"2019","journal-title":"Thorax"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"3277","DOI":"10.1007\/s00330-020-06727-7","article-title":"European Society of Radiology and the European Respiratory Society. ESR\/ERS statement paper on lung cancer screening","volume":"30","author":"Kauczor","year":"2020","journal-title":"Eur. Radiol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.lungcan.2018.10.029","article-title":"The cost-effectiveness of the Manchester \u2018lung health checks\u2019, a community-based lung cancer low-dose CT screening pilot","volume":"126","author":"Hinde","year":"2018","journal-title":"Lung Cancer"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1136\/thorax-2023-220001","article-title":"Invitation strategies and participation in a community-based lung cancer screening programme located in areas of high socioeconomic deprivation","volume":"79","author":"Goodley","year":"2023","journal-title":"Thorax"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1186\/s12960-020-00520-9","article-title":"The association between the workload of general practitioners and patient experiences with care: Results of a cross-sectional study in 33 countries","volume":"18","author":"Groenewegen","year":"2020","journal-title":"Hum. Resour. Health"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1093\/fampra\/cmab180","article-title":"The global prevalence of burnout among general practitioners: A systematic review and meta-analysis","volume":"39","author":"Shen","year":"2022","journal-title":"Fam. Pract."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1186\/s13643-019-1170-x","article-title":"Strategies for increasing participation in mail-out colorectal cancer screening programs: A systematic review and meta-analysis","volume":"8","author":"Goodwin","year":"2019","journal-title":"Syst. Rev."},{"key":"ref_67","unstructured":"(2023, September 13). Lung-RADS Category Descriptor Findings Management 0. Available online: https:\/\/www.acr.org\/Clinical-Resources\/Reporting-and-Data-Systems\/Lung-Rads."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"776","DOI":"10.7326\/0003-4819-157-11-201212040-00005","article-title":"Estimating overdiagnosis in low-dose computed tomography screening for lung cancer: A cohort study","volume":"157","author":"Veronesi","year":"2012","journal-title":"Ann. Intern. Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2038","DOI":"10.1016\/j.jtcvs.2018.11.139","article-title":"Do the surgical results in the National Lung Screening Trial reflect modern thoracic surgical practice?","volume":"157","author":"Kamel","year":"2019","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1016\/S1010-7940(01)00841-7","article-title":"Acute phase responses following minimal access and conventional thoracic surgery","volume":"20","author":"Craig","year":"2001","journal-title":"Eur. J. Cardio-Thorac. Surg."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1093\/icvts\/ivaa296","article-title":"Immune profiling after minimally invasive lobectomy","volume":"32","author":"Erus","year":"2021","journal-title":"Interact. Cardiovasc. Thorac. Surg."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1007\/s12055-021-01301-2","article-title":"Systemic inflammatory changes and their clinical implications following thoracic cancer surgery","volume":"38","author":"Fornasiero","year":"2022","journal-title":"Indian J. Thorac. Cardiovasc. Surg."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1055\/s-0042-1744546","article-title":"Comparison of Chronic Postsurgical Pain Between Single-Port and Multi-Port Video-Assisted Thoracoscopic Pulmonary Resection: A Prospective Study","volume":"70","author":"Jin","year":"2022","journal-title":"Thorac. Cardiovasc. Surg."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"34","DOI":"10.21037\/ccts-22-10","article-title":"Patient perspectives on open vs. minimally invasive thoracic surgery (PPOMITS): Survey and experience from a single academic institution","volume":"5","author":"Jones","year":"2023","journal-title":"Curr. Chall. Thorac. Surg."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"11","DOI":"10.21037\/shc-23-4","article-title":"Minimally invasive thoracic surgery the price of the chase for innovation?\u2014Or a real functional and oncological improvement?","volume":"7","author":"Montagne","year":"2023","journal-title":"Shanghai Chest."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Detterbeck, F.C., Antonicelli, A., and Okada, M. (2017). Results of Video-Assisted Techniques for Resection of Lung Cancer. IASLC Thoracic Oncol. E-Book, 274\u2013282.","DOI":"10.1016\/B978-0-323-52357-8.00027-5"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Marchegiani, F., Siragusa, L., Zadoroznyj, A., Laterza, V., Mangana, O., Schena, C.A., Ammendola, M., Memeo, R., Bianchi, P.P., and Spinoglio, G. (2023). New Robotic Platforms in General Surgery: What\u2019s the Current Clinical Scenario?. Medicina, 59.","DOI":"10.3390\/medicina59071264"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1016\/S0140-6736(21)02333-3","article-title":"West Japan Oncology Group and Japan Clinical Oncology Group. Segmentectomy versus lobectomy in small-sized peripheral non-small-cell lung cancer (JCOG0802\/WJOG4607L): A multicentre, open-label, phase 3, randomised, controlled, non-inferiority trial","volume":"399","author":"Saji","year":"2022","journal-title":"Lancet"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1056\/NEJMoa2212083","article-title":"Lobar or Sublobar Resection for Peripheral Stage IA Non-Small-Cell Lung Cancer","volume":"388","author":"Altorki","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1183\/09031936.00066514","article-title":"Positron emission tomography in the diagnostic work-up of screening-detected lung nodules","volume":"45","author":"Veronesi","year":"2015","journal-title":"Eur. Respir. J."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1136\/bmj.j347","article-title":"Exposure to low dose computed tomography for lung cancer screening and risk of cancer: Secondary analysis of trial data and risk-benefit analysis","volume":"356","author":"Rampinelli","year":"2017","journal-title":"BMJ"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1097\/CEJ.0b013e328351e1b6","article-title":"Annual or biennial CT screening versus observation in heavy smokers: 5-year results of the MILD trial","volume":"21","author":"Pastorino","year":"2012","journal-title":"Eur. J. Cancer Prev."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Veronesi, G., Baldwin, D.R., Henschke, C.I., Ghislandi, S., Iavicoli, S., Oudkerk, M., De Konig, H.J., Shemesh, J., Field, J.K., and Zulueta, J.J. (2020). Recommendations for Implementing Lung Cancer Screening with Low-Dose Computed Tomography in Europe. Cancers, 12.","DOI":"10.3390\/cancers12061672"},{"key":"ref_84","unstructured":"(2023, October 11). Improving Cancer Screening in the European Union\u2014Scientific Advice Mechanism. Available online: https:\/\/scientificadvice.eu\/advice\/improving-cancer-screening-in-the-european-union\/."},{"key":"ref_85","unstructured":"European Commission, Directorate-General for Research and Innovation, European Commission, and Group of Chief Scientific Advisors (2022). Cancer Screening in the European Union."},{"key":"ref_86","unstructured":"European Commission Group of Chief Scientific Advisors (2022). Improving Cancer Screening in the European Union. Sci. Advice Policy Eur. Acad., 158, 1677. Available online: https:\/\/sapea.info\/wp-content\/uploads\/cancer-screening-report.pdf."},{"key":"ref_87","unstructured":"(2023, October 14). Cancer Screening in the European Union\u2014Publications Office of the, E.U. Available online: https:\/\/op.europa.eu\/en\/publication-detail\/-\/publication\/519a9bf4-9f5b-11ec-83e1-01aa75ed71a1."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"347","DOI":"10.21037\/tlcr.2018.05.04","article-title":"Chronic obstructive pulmonary disease (COPD) and lung cancer screening","volume":"7","author":"Young","year":"2018","journal-title":"Transl. Lung Cancer Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"160","DOI":"10.21037\/atm.2016.03.57","article-title":"Lung cancer screening in patients with chronic obstructive pulmonary disease","volume":"4","author":"Gonzalez","year":"2016","journal-title":"Ann. Transl. Med."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1097\/RTI.0000000000000379","article-title":"Screening for Early Lung Cancer, Chronic Obstructive Pulmonary Disease, and Cardiovascular Disease (the Big-3) Using Low-dose Chest Computed Tomography: Current Evidence and Technical Considerations","volume":"34","author":"Heuvelmans","year":"2019","journal-title":"J. Thorac. Imaging"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"S223","DOI":"10.1016\/j.jtho.2023.09.365","article-title":"P1.17-04 Lung-Cancer Screening: Is It Worth Investing? Evidence from a Population-Based Markov Study in Italy","volume":"18","author":"Ghislandi","year":"2023","journal-title":"J. Thorac. Oncol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.jtho.2017.10.012","article-title":"Cost-Effectiveness of Osimertinib for EGFR Mutation-Positive Non-Small Cell Lung Cancer after Progression following First-Line EGFR TKI Therapy","volume":"13","author":"Wu","year":"2018","journal-title":"J. Thorac. Oncol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1634\/theoncologist.2018-0150","article-title":"Cost-Effectiveness of Osimertinib in Treating Newly Diagnosed, Advanced EGFR-Mutation-Positive Non-Small Cell Lung Cancer","volume":"24","author":"Wu","year":"2019","journal-title":"Oncologist"},{"key":"ref_94","first-page":"272","article-title":"Offering Lung Cancer Screening to High-Risk Medicare Beneficiaries Saves Lives and Is Cost-Effective: An Actuarial Analysis","volume":"7","author":"Pyenson","year":"2014","journal-title":"Am. Health Drug Benefits"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1136\/thoraxjnl-2015-207140","article-title":"UK Lung Cancer RCT Pilot Screening Trial: Baseline findings from the screening arm provide evidence for the potential implementation of lung cancer screening","volume":"71","author":"Field","year":"2016","journal-title":"Thorax"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1080\/13696998.2017.1377718","article-title":"Cost-effectiveness of osimertinib in the UK for advanced EGFR-T790M non-small cell lung cancer","volume":"21","author":"Bertranou","year":"2018","journal-title":"J. Med. Econ."},{"key":"ref_97","first-page":"1201","article-title":"Lifetime Smoking History and Risk of Lung Cancer: Results From the Framingham Heart Study","volume":"110","author":"Tindle","year":"2018","journal-title":"J. Natl. Cancer Inst."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/16\/2\/417\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:49:56Z","timestamp":1760104196000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/16\/2\/417"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,18]]},"references-count":97,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2024,1]]}},"alternative-id":["cancers16020417"],"URL":"https:\/\/doi.org\/10.3390\/cancers16020417","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,18]]}}}