1. Cohort construction: A prospective observational cohort of patients with resectable stage IB-III non-small cell lung cancer scheduled to receive neoadjuvant chemoimmunotherapy followed by curative-intent surgery will be established. Clinical, pathological, and radiological data will be collected prospectively, including radiologic response during neoadjuvant treatment and pathologic response (major pathologic response and pathologic complete response) in the resected specimen.
2. Tissue-based biomarkers: Pretreatment tumor tissue obtained at diagnosis will undergo comprehensive genomic profiling using a targeted next-generation sequencing panel to identify actionable genomic alterations, copy-number alterations (including PD-L1/CD274), and other genomic features potentially associated with response or resistance to neoadjuvant chemoimmunotherapy. These findings will be evaluated together with routine biomarkers, including PD-L1 immunohistochemistry.
3. Blood-based biomarkers: Plasma will be collected serially from individual patients at multiple time points, including before neoadjuvant treatment, during neoadjuvant treatment (e.g., after 2 cycles), before surgery, and during postoperative follow-up. Circulating tumor DNA (ctDNA) analysis will be performed to evaluate (a) on-treatment ctDNA dynamics as a non-invasive predictor of pathologic response before surgery and (b) postoperative ctDNA as a marker of molecular residual disease and recurrence risk.
4. Study conduct: This is a non-interventional study. All patients will receive treatment according to standard clinical practice, and study-related test results will not be used to modify treatment. Tissue and blood biomarkers will be correlated with pathologic response and with long-term outcomes, including event-free survival.
