Lung Cancer Screening in Population Who Had Never Smoked

Overview

Study design: prospective, single arm. Objectives: survey lung cancer detection rate of low-dose computed tomography (LDCT) screening in individuals who had never smoked. Participants will undergo questionnaires, and collecting specimens including blood, urine, and medical informations including results of pulmonary function tests, and LDCT screening upon inclusion. The participants will be followed up according to current standards of clinical practice.

Lung cancer remains the leading cause of cancer-related mortality worldwide, with a particularly high incidence and mortality rate in Taiwan. Notably, over half of lung cancer cases in Taiwan occur among individuals who have never smoked, a pattern distinct from Western populations. In response to this unique epidemiological profile, this project aims to promote community-based lung cancer screening among never-smokers and to validate the FORMOSA lung cancer risk prediction model, which integrates demographic, environmental, genetic, and clinical factors. This prospective, single-arm, open-label study will recruit approximately 2,500 participants aged 40 to 80 years with no history of smoking, through hospital and community outreach. Eligible participants will provide informed consent and undergo comprehensive assessments, including questionnaires on lifestyle and environmental exposures, low-dose computed tomography (LDCT), chest X-ray, pulmonary function tests, and collection of blood and urine samples. LDCT results will be interpreted according to the modified ACR Lung-RADS v1.1 criteria. Biological specimens will be used for biomarker, heavy metal, genetic, and proteomic analyses. Participants with abnormal findings will be followed according to standard clinical protocols, and tissue samples from invasive procedures will be retained for further molecular studies. The primary outcomes include the lung cancer detection rate among never-smoked participants and the validation metrics (sensitivity, specificity, positive and negative predictive values) of the FORMOSA lung cancer risk prediction model. Statistical analyses will employ descriptive statistics, Kaplan-Meier survival analysis, log-rank tests, Cox proportional hazards models, and group comparisons using ANOVA, Kruskal-Wallis, chi-square, Fisher's exact tests, and logistic-regression. Preliminary data suggest that the FORMOSA model can identify high-risk individuals with a lung cancer detection rate of 2.8-3.3%, significantly higher than the general population rate of 0.78%. This project is expected to enhance early detection of lung cancer in never-smokers, improve public awareness, and establish a robust epidemiological database for Taiwan. The validation of the FORMOSA model will provide a scientific basis for refining screening strategies and inform future public health policies targeting high-risk, non-smoking populations. The study is conducted with strict adherence to ethical standards, ensuring participant rights and data security. Funding is provided by the Ministry of Health and Welfare's "Healthy Taiwan Deep Cultivation Plan." In summary, this research addresses a critical gap in lung cancer prevention by focusing on never-smokers, leveraging a comprehensive risk prediction model, and implementing a community-based screening approach. The anticipated outcomes will contribute significantly to reducing late-stage lung cancer diagnoses and mortality, and serve as a reference for future health policy development in Taiwan and similar populations.