{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T13:26:07Z","timestamp":1772717167669,"version":"3.50.1"},"reference-count":46,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T00:00:00Z","timestamp":1747353600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Champalimaud Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Lung cancer (LC) is the leading cause of cancer-related deaths worldwide. Effective screening strategies for early diagnosis that could improve disease prognosis are lacking. Non-invasive breath analysis of volatile organic compounds (VOC) is a potential method for earlier LC detection. This study explores the association of VOC profiles with artificial intelligence (AI) to achieve a sensitive, specific, and fast method for LC detection. Patients and methods: Exhaled breath air samples were collected from 123 healthy individuals and 73 LC patients at two clinical sites. The enrolled patients had LC diagnosed with different stages. Breath samples were collected before undergoing any treatment, including surgery, and analyzed using gas chromatography coupled to ion-mobility spectrometry (GC-IMS). AI methods classified the overall chromatographic profiles. Results: GC-IMS is highly sensitive, yielding detailed chromatographic profiles. AI methods ranked the sets of exhaled breath profiles across both groups through training and validation steps, while qualitative information was deliberately not taking part nor influencing the results. The K-nearest neighbor (KNN) algorithm classified the groups with an accuracy of 90% (sensitivity = 87%, specificity = 92%). Narrowing the LC group to those only in early-stage IA, the accuracy was 90% (sensitivity = 90%, specificity = 93%). Conclusions: Evaluation of the global exhaled breath profiles using AI algorithms enabled LC detection and demonstrated that qualitative information may not be required, thus easing the frustration that many studies have experienced so far. The results show that this approach coupled with screening protocols may improve earlier detection of LC and hence its prognosis.<\/jats:p>","DOI":"10.3390\/cancers17101685","type":"journal-article","created":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T09:30:38Z","timestamp":1747387838000},"page":"1685","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Breath Insights: Advancing Lung Cancer Early-Stage Detection Through AI Algorithms in Non-Invasive VOC Profiling Trials"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8154-3872","authenticated-orcid":false,"given":"Bernardo S.","family":"Raimundo","sequence":"first","affiliation":[{"name":"Unidade de Pulm\u00e3o, Centro Cl\u00ednico Champalimaud, Funda\u00e7\u00e3o Champalimaud, 1400-038 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-6358-9997","authenticated-orcid":false,"given":"Pedro M.","family":"Leit\u00e3o","sequence":"additional","affiliation":[{"name":"Departamento de Engenharia Electrot\u00e9cnica e de Computadores, Faculdade de Ci\u00eancias e Tecnologia, Universidade Nova de Lisboa, Quinta da Torre, 2829-516 Caparica, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-7467-1339","authenticated-orcid":false,"given":"Manuel","family":"Vinhas","sequence":"additional","affiliation":[{"name":"Departamento de Engenharia Electrot\u00e9cnica e de Computadores, Faculdade de Ci\u00eancias e Tecnologia, Universidade Nova de Lisboa, Quinta da Torre, 2829-516 Caparica, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-6835-310X","authenticated-orcid":false,"given":"Maria V.","family":"Pires","sequence":"additional","affiliation":[{"name":"Unidade de Pulm\u00e3o, Centro Cl\u00ednico Champalimaud, Funda\u00e7\u00e3o Champalimaud, 1400-038 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0557-6437","authenticated-orcid":false,"given":"Laura B.","family":"Quintas","sequence":"additional","affiliation":[{"name":"Unidade de Pulm\u00e3o, Centro Cl\u00ednico Champalimaud, Funda\u00e7\u00e3o Champalimaud, 1400-038 Lisboa, Portugal"}]},{"given":"Catarina","family":"Carvalheiro","sequence":"additional","affiliation":[{"name":"Unidade de Pulm\u00e3o, Centro Cl\u00ednico Champalimaud, Funda\u00e7\u00e3o Champalimaud, 1400-038 Lisboa, Portugal"}]},{"given":"Rita","family":"Barata","sequence":"additional","affiliation":[{"name":"Unidade de Pulm\u00e3o, Centro Cl\u00ednico Champalimaud, Funda\u00e7\u00e3o Champalimaud, 1400-038 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5297-4515","authenticated-orcid":false,"given":"Joana","family":"Ip","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Radiologia, Centro Cl\u00ednico Champalimaud, Funda\u00e7\u00e3o Champalimaud, 1400-038 Lisboa, Portugal"}]},{"given":"Ricardo","family":"Coelho","sequence":"additional","affiliation":[{"name":"Unidade de Pulm\u00e3o, Centro Cl\u00ednico Champalimaud, Funda\u00e7\u00e3o Champalimaud, 1400-038 Lisboa, Portugal"}]},{"given":"Sofia","family":"Granadeiro","sequence":"additional","affiliation":[{"name":"Unidade de Pulm\u00e3o, Centro Cl\u00ednico Champalimaud, Funda\u00e7\u00e3o Champalimaud, 1400-038 Lisboa, Portugal"}]},{"given":"T\u00e2nia S.","family":"Sim\u00f5es","sequence":"additional","affiliation":[{"name":"Unidade de Pulm\u00e3o, Centro Cl\u00ednico Champalimaud, Funda\u00e7\u00e3o Champalimaud, 1400-038 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7873-0087","authenticated-orcid":false,"given":"Jo\u00e3o","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Unidade de Pulm\u00e3o, Centro Cl\u00ednico Champalimaud, Funda\u00e7\u00e3o Champalimaud, 1400-038 Lisboa, Portugal"}]},{"given":"Renato","family":"Bai\u00e3o","sequence":"additional","affiliation":[{"name":"Unidade de Pulm\u00e3o, Centro Cl\u00ednico Champalimaud, Funda\u00e7\u00e3o Champalimaud, 1400-038 Lisboa, Portugal"}]},{"given":"Carla","family":"Rocha","sequence":"additional","affiliation":[{"name":"Unidade de Pulm\u00e3o, Centro Cl\u00ednico Champalimaud, Funda\u00e7\u00e3o Champalimaud, 1400-038 Lisboa, Portugal"}]},{"given":"Sandra","family":"Alves","sequence":"additional","affiliation":[{"name":"Unidade de Ensaios Cl\u00ednicos, Centro Cl\u00ednico Champalimaud, Funda\u00e7\u00e3o Champalimaud, 1400-038 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7199-3810","authenticated-orcid":false,"given":"Paulo","family":"Fidalgo","sequence":"additional","affiliation":[{"name":"Unidade de Risco e Diagn\u00f3stico Precoce, Centro Cl\u00ednico Champalimaud, Funda\u00e7\u00e3o Champalimaud, 1400-038 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2673-868X","authenticated-orcid":false,"given":"Al\u00edpio","family":"Ara\u00fajo","sequence":"additional","affiliation":[{"name":"Unidade de Risco e Diagn\u00f3stico Precoce, Centro Cl\u00ednico 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Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7863-8069","authenticated-orcid":false,"given":"Marcos","family":"Pantarotto","sequence":"additional","affiliation":[{"name":"Unidade de Pulm\u00e3o, Centro Cl\u00ednico Champalimaud, Funda\u00e7\u00e3o Champalimaud, 1400-038 Lisboa, Portugal"}]},{"given":"Lu\u00eds","family":"Carreiro","sequence":"additional","affiliation":[{"name":"Unidade de Pulm\u00e3o, Centro Cl\u00ednico Champalimaud, Funda\u00e7\u00e3o Champalimaud, 1400-038 Lisboa, Portugal"}]},{"given":"Rog\u00e9rio","family":"Matos","sequence":"additional","affiliation":[{"name":"Unidade de Pulm\u00e3o, Centro Cl\u00ednico Champalimaud, Funda\u00e7\u00e3o Champalimaud, 1400-038 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0915-4105","authenticated-orcid":false,"given":"Cristina","family":"B\u00e1rbara","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Pneumologia, Centro Hospitalar e Universit\u00e1rio Lisboa Norte, 1649-035 Lisboa, Portugal"}]},{"given":"Jorge","family":"Cruz","sequence":"additional","affiliation":[{"name":"Unidade de Pulm\u00e3o, Centro Cl\u00ednico Champalimaud, Funda\u00e7\u00e3o Champalimaud, 1400-038 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6567-8379","authenticated-orcid":false,"given":"Nuno","family":"Gil","sequence":"additional","affiliation":[{"name":"Unidade de Pulm\u00e3o, Centro Cl\u00ednico Champalimaud, Funda\u00e7\u00e3o Champalimaud, 1400-038 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9220-6046","authenticated-orcid":false,"given":"Fernando","family":"Luis-Ferreira","sequence":"additional","affiliation":[{"name":"Departamento de Engenharia Electrot\u00e9cnica e de Computadores, Faculdade de Ci\u00eancias e Tecnologia, Universidade Nova de Lisboa, Quinta da Torre, 2829-516 Caparica, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9720-9801","authenticated-orcid":false,"given":"Pedro 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