Abstract Background Patients with chronic obstructive pulmonary disease (COPD) are at increased risk of lung cancer, and the identification of circulating tumor DNA (ctDNA) mutations may help detect lung cancer in them. However, whether the addition of ctDNA information improves lung cancer prediction remains to be elucidated. Method Blood samples from 236 patients with COPD (119 with lung cancer and 117 without lung cancer) were genotyped using targeted deep sequencing. With 39 clinical and genomic/molecular variables, nine machine learning (ML) models to predict lung cancer were constructed. Prediction performances were compared between models with clinical variables only and those with additional genomic/molecular variables. Results Three clinical variables (smoking amount, C-reactive protein CRP, COPD symptom burden) and four genomic/molecular variables (ctDNA mutation detected, lung cancer driver gene, max variant allele frequency, and median duplex) were significantly associated with lung cancer (P 0.05). Notably, four of the nine ML models, incorporating clinical and genomic/molecular variables, outperformed models using clinical variables alone (AUC of the best models = 0.729 vs. 0.620, P 0.05). Conclusion Integration of ctDNA information may enhance risk stratification strategies for lung cancer among COPD patients. This abstract is funded by: The National Research Foundation of Korea (NRF) grant funded by the Korean Government, Ministry of Science and Information Communication Technologies (Nos. NRF-2021R1A4A5032806, NRF-2021R1A6A1A03038899, NRF-2019R1A2C4070496, and NRF-2017M3A9G5060264), and the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) funded by the Korean Government, Ministry of Health and Welfare (Nos. RS-2020-KH088686 and RS-2025-02216473)
Shin et al. (2026) studied this question.