{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T21:51:02Z","timestamp":1791841862582,"version":"4.3.4"},"reference-count":49,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T00:00:00Z","timestamp":1752105600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Victor Babes University of Medicine and Pharmacy, Eftimie Murgu Square 2, 300041, Timisoara, Romania","award":["1685\/26.01.2024"],"award-info":[{"award-number":["1685\/26.01.2024"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Lung cancer remains a major cause of cancer-related mortality, with regional differences in incidence and patient characteristics. This study aimed to verify and quantify a perceived dramatic increase in lung cancer cases at a Romanian center, identify distinct patient phenotypes using unsupervised machine learning, and characterize contributing factors, including demographic shifts, changes in the healthcare system, and geographic patterns. Methods: A comprehensive retrospective analysis of 4206 lung cancer patients admitted between 2013 and 2024 was conducted, with detailed molecular characterization of 398 patients from 2023 to 2024. Temporal trends were analyzed using statistical methods, while k-means clustering on 761 clinical features identified patient phenotypes. The geographic distribution, smoking patterns, respiratory comorbidities, and demographic factors were systematically characterized across the identified clusters. Results: We confirmed an 80.5% increase in lung cancer admissions between pre-pandemic (2013\u20132020) and post-pandemic (2022\u20132024) periods, exceeding the 51.1% increase in total hospital admissions and aligning with national Romanian trends. Five distinct patient clusters emerged: elderly never-smokers (28.9%) with the highest metastatic rates (44.3%), heavy-smoking males (27.4%), active smokers with comprehensive molecular testing (31.7%), young mixed-gender cohort (7.3%) with balanced demographics, and extreme heavy smokers (4.8%) concentrated in rural areas (52.6%) with severe comorbidity burden. Clusters demonstrated significant differences in age (p &lt; 0.001), smoking intensity (p &lt; 0.001), geographic distribution (p &lt; 0.001), as well as molecular characteristics. COPD prevalence was exceptionally high (44.8\u201378.9%) across clusters, while COVID-19 history remained low (3.4\u20138.3%), suggesting a limited direct association between the pandemic and cancer. Conclusions: This study presents the first comprehensive machine learning-based stratification of lung cancer patients in Romania, confirming genuine epidemiological increases beyond healthcare system artifacts. The identification of five clinically meaningful phenotypes\u2014particularly rural extreme smokers and age-stratified never-smokers\u2014demonstrates the value of unsupervised clustering for regional healthcare planning. These findings establish frameworks for targeted screening programs, personalized treatment approaches, and resource allocation strategies tailored to specific high-risk populations while highlighting the potential of artificial intelligence in identifying actionable clinical patterns for the implementation of precision medicine.<\/jats:p>","DOI":"10.3390\/cancers17142305","type":"journal-article","created":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T08:15:47Z","timestamp":1752221747000},"page":"2305","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Temporal Trends and Patient Stratification in Lung Cancer: A Comprehensive Clustering Analysis from Timis County, Romania"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4840-1925","authenticated-orcid":false,"given":"Versavia Maria","family":"Ancusa","sequence":"first","affiliation":[{"name":"Department of Computer and Information Technology, Automation and Computers Faculty, \u201cPolitehnica\u201d University of Timisoara, Vasile P\u00e2rvan Blvd, no. 2, 300223 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5270-1464","authenticated-orcid":false,"given":"Ana Adriana","family":"Trusculescu","sequence":"additional","affiliation":[{"name":"Center for Research and Innovation in Personalized Medicine of Respiratory Diseases (CRIPMRD), \u2018Victor Babes\u2019 University of Medicine and Pharmacy, Eftimie Murgu Square no. 2, 300041 Timisoara, Romania"},{"name":"Pulmonology University Clinic, Clinical Hospital of Infectious Diseases and Pneumophysiology, Dr. Victor Babe\u0219 Timi\u0219oara, Gheorghe Adam Street, no. 13, 300310 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-7606-6001","authenticated-orcid":false,"given":"Amalia","family":"Constantinescu","sequence":"additional","affiliation":[{"name":"Center for Research and Innovation in Personalized Medicine of Respiratory Diseases (CRIPMRD), \u2018Victor Babes\u2019 University of Medicine and Pharmacy, Eftimie Murgu Square no. 2, 300041 Timisoara, Romania"},{"name":"Doctoral School, \u201cVictor Babes\u201d University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, 300041 Timisoara, Romania"},{"name":"Radiology and Medical Imaging University Clinic, Clinical Hospital of Infectious Diseases and Pneumophysiology, Dr. Victor Babe\u0219 Timi\u0219oara, Gheorghe Adam Street, no. 13, 300310 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Burducescu","sequence":"additional","affiliation":[{"name":"Pulmonology University Clinic, Clinical Hospital of Infectious Diseases and Pneumophysiology, Dr. Victor Babe\u0219 Timi\u0219oara, Gheorghe Adam Street, no. 13, 300310 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9034-5218","authenticated-orcid":false,"given":"Ovidiu","family":"Fira-Mladinescu","sequence":"additional","affiliation":[{"name":"Center for Research and Innovation in Personalized Medicine of Respiratory Diseases (CRIPMRD), \u2018Victor Babes\u2019 University of Medicine and Pharmacy, Eftimie Murgu Square no. 2, 300041 Timisoara, Romania"},{"name":"Pulmonology University Clinic, Clinical Hospital of Infectious Diseases and Pneumophysiology, Dr. Victor Babe\u0219 Timi\u0219oara, Gheorghe Adam Street, no. 13, 300310 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4602-7730","authenticated-orcid":false,"given":"Diana Lumita","family":"Manolescu","sequence":"additional","affiliation":[{"name":"Center for Research and Innovation in Personalized Medicine of Respiratory Diseases (CRIPMRD), \u2018Victor Babes\u2019 University of Medicine and Pharmacy, Eftimie Murgu Square no. 2, 300041 Timisoara, Romania"},{"name":"Radiology and Medical Imaging University Clinic, Clinical Hospital of Infectious Diseases and Pneumophysiology, Dr. Victor Babe\u0219 Timi\u0219oara, Gheorghe Adam Street, no. 13, 300310 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Traila","sequence":"additional","affiliation":[{"name":"Center for Research and Innovation in Personalized Medicine of Respiratory Diseases (CRIPMRD), \u2018Victor Babes\u2019 University of Medicine and Pharmacy, Eftimie Murgu Square no. 2, 300041 Timisoara, Romania"},{"name":"Pulmonology University Clinic, Clinical Hospital of Infectious Diseases and Pneumophysiology, Dr. Victor Babe\u0219 Timi\u0219oara, Gheorghe Adam Street, no. 13, 300310 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0749-8232","authenticated-orcid":false,"given":"Norbert","family":"Wellmann","sequence":"additional","affiliation":[{"name":"Center for Research and Innovation in Personalized Medicine of Respiratory Diseases (CRIPMRD), \u2018Victor Babes\u2019 University of Medicine and Pharmacy, Eftimie Murgu Square no. 2, 300041 Timisoara, Romania"},{"name":"Pulmonology University Clinic, Clinical Hospital of Infectious Diseases and Pneumophysiology, Dr. Victor Babe\u0219 Timi\u0219oara, Gheorghe Adam Street, no. 13, 300310 Timisoara, Romania"},{"name":"Doctoral School, \u201cVictor Babes\u201d University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristian Iulian","family":"Oancea","sequence":"additional","affiliation":[{"name":"Center for Research and Innovation in Personalized Medicine of Respiratory Diseases (CRIPMRD), \u2018Victor Babes\u2019 University of Medicine and Pharmacy, Eftimie Murgu Square no. 2, 300041 Timisoara, Romania"},{"name":"Pulmonology University Clinic, Clinical Hospital of Infectious Diseases and Pneumophysiology, Dr. Victor Babe\u0219 Timi\u0219oara, Gheorghe Adam Street, no. 13, 300310 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"102693","DOI":"10.1016\/j.canep.2024.102693","article-title":"Global burden of lung cancer in 2022 and projections to 2050: Incidence and mortality estimates from GLOBOCAN","volume":"93","author":"Zhou","year":"2024","journal-title":"Cancer Epidemiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"229","DOI":"10.3322\/caac.21834","article-title":"Global cancer statistics 2022: GLOBOCAN 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