Lung Cancer Screening in Population Who Had Never Smoked

Official title

Lung Cancer Screening in Population Who Had Never Smoked and the Validation of Lung Cancer Risk Prediction Model

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.

Detailed description

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.

Interventions

• Diagnostic test Low dose computed tomography
  Low dose computed tomography for lung cancer screening

Primary outcome measures

• Lung cancer detection rate [Time frame: 8 years of follow-up]

Secondary outcome measures (1)

• AUROC of FORMOSA Lung Cancer Risk Prediction Model [Time frame: 8 years]

Eligibility criteria

Inclusion criteria

• Individuals with no history of smoking.
• Aged 40 to 80 years.
• Willing to provide written informed consent and complete questionnaire assessments.
• After undergoing examinations, willing to provide relevant biological information, including but not limited to: blood samples, urine samples, pulmonary function test results, imaging data, and tissue specimens obtained from invasive biopsies or surgical procedures (if applicable).

Exclusion criteria

• History of lung cancer, or a diagnosis of any malignancy other than skin cancer or cervical carcinoma in situ within the past five years.
• Undergoing chest computed tomography (CT) scans within the past 18 months.
• Unexplained hemoptysis within the past one month.
• Unexplained weight loss exceeding 6 kilograms within the past one year.
• Pregnancy.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Screening

Study locations

Center list to be confirmed — check the primary protocol.

Publications

• Shi J, Shiraishi K, Choi J, Matsuo K, Chen TY, Dai J, Hung RJ, Chen K, Shu XO, Kim YT, Landi MT, Lin D, Zheng W, Yin Z, Zhou B, Song B, Wang J, Seow WJ, Song L, Chang IS, Hu W, Chien LH, Cai Q, Hong YC, Kim HN, Wu YL, Wong MP, Richardson BD, Funderburk KM, Li S, Zhang T, Breeze C, Wang Z, Blechter B, Bassig BA, Kim JH, Albanes D, Wong JYY, Shin MH, Chung LP, Yang Y, An SJ, Zheng H, Yatabe Y, Zhang PMID 37236969
• Diaz-Gay M, Zhang T, Hoang PH, Leduc C, Baine MK, Travis WD, Sholl LM, Joubert P, Khandekar A, Zhao W, Steele CD, Otlu B, Nandi SP, Vangara R, Bergstrom EN, Kazachkova M, Pich O, Swanton C, Hsiung CA, Chang IS, Wong MP, Leung KC, Sang J, McElderry JP, Hartman C, Colon-Matos FJ, Miraftab M, Saha M, Lee OW, Jones KM, Gallego-Garcia P, Yang Y, Zhong X, Edell ES, Santamaria JM, Schabath MB, Yendamuri PMID 40604281
• Chen IC, Chen YM, Yang HW, Tseng JS, Yang TY. Interplay of Polygenic Risk Score, Smoking Statuses, and Air Pollution on Lung Adenocarcinoma Risk in a Taiwanese Population. Respirology. 2025 Apr;30(4):317-325. doi: 10.1111/resp.70004. Epub 2025 Feb 16. PMID 39956994
• Blechter B, Chien LH, Chen TY, Chang IS, Choudhury PP, Hsiao CF, Shu XO, Wong JYY, Chen KY, Chang GC, Tsai YH, Su WC, Huang MS, Chen YM, Chen CY, Hung HH, Hu JW, Shi J, Zheng W, Rositch AF, Chen CJ, Chatterjee N, Yang PC, Rothman N, Hsiung CA, Lan Q. Polygenic Risk Score, Environmental Tobacco Smoke, and Risk of Lung Adenocarcinoma in Never-Smoking Women in Taiwan. JAMA Netw Open. 2023 Nov 1;6(11) PMID 37955902
• Blechter B, Wong JYY, Agnes Hsiung C, Hosgood HD, Yin Z, Shu XO, Zhang H, Shi J, Song L, Song M, Zheng W, Wang Z, Caporaso N, Burdette L, Yeager M, Berndt SI, Teresa Landi M, Chen CJ, Chang GC, Hsiao CF, Tsai YH, Chen KY, Huang MS, Su WC, Chen YM, Chien LH, Chen CH, Yang TY, Wang CL, Hung JY, Lin CC, Perng RP, Chen CY, Chen KC, Li YJ, Yu CJ, Chen YS, Chen YH, Tsai FY, Jie Seow W, Bassig BA, Hu W, PMID 33385923
• Coradduzza D, Congiargiu A, Azara E, Mammani IMA, De Miglio MR, Zinellu A, Carru C, Medici S. Heavy metals in biological samples of cancer patients: a systematic literature review. Biometals. 2024 Aug;37(4):803-817. doi: 10.1007/s10534-024-00583-4. Epub 2024 Feb 12. PMID 38347295
• Lee NW, Wang HY, Du CL, Yuan TH, Chen CY, Yu CJ, Chan CC. Air-polluted environmental heavy metal exposure increase lung cancer incidence and mortality: A population-based longitudinal cohort study. Sci Total Environ. 2022 Mar 1;810:152186. doi: 10.1016/j.scitotenv.2021.152186. Epub 2021 Dec 6. PMID 34883183
• Huang HH, Huang JY, Lung CC, Wu CL, Ho CC, Sun YH, Ko PC, Su SY, Chen SC, Liaw YP. Cell-type specificity of lung cancer associated with low-dose soil heavy metal contamination in Taiwan: an ecological study. BMC Public Health. 2013 Apr 10;13:330. doi: 10.1186/1471-2458-13-330. PMID 23575356

Identifiers

NCT: NCT07383454 · CS1-26008

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗