The goal of this observational study is to explore whether ctDNA-MRD dynamic monitoring can more effectively predict the therapeutic effect of induction chemoimmunotherapy followed by surgery or non-surgical treatment for stage IIIB-C driver-negative NSCLC in the MDT model, so as to accurately guide clinical diagnosis and treatment.

This study is a single-center, observational, non-interventional, prospective study. 50 patients diagnosed with stage IIIB-C driver-negative NSCLC receiving induction chemoimmunotherapy will be planned to be enrolled in the study. Pre-treatment biopsy tissues of enrolled patients will be collected for next-generation sequencing (NGS) of institutionally-developed 1021-gene panel, and personalized detection panel will be customized based on NGS testing results. Patients will be received induction chemoimmunotherapy followed by surgery or non-surgical treatment in the MDT model and ctDNA-MRD testing will be performed at prespecified time points. For patients who received surgery following induction therapy, peripheral blood will be collected in baseline, 1 day before the third cycle of neoadjuvant therapy, 1 day before surgery, 3 days after surgery and landmark time and pulmonary venous blood will be collected intraoperatively. For patients who received non-surgical treatment following induction therapy, peripheral blood will be collected in baseline, 1 day before the third cycle of neoadjuvant therapy, 1 day before non-surgical therapy and landmark time. All included patients will be regularly followed up for at least 5 years.

Inclusion Criteria:

• Histopathology or cytology confirmed the non-small cell lung cancer
• Age ranging from 18 to 75
• Agree to participate in this study and sign an informed consent form
• Treatment-naive tumor
• Driver gene negativity
• According to the American Joint Committee on Cancer (AJCC) eighth edition of the Lung Cancer Staging Manual, the clinical stage is stage IIIB-C potentially resectable tumor
• The Eastern Cooperative Oncology Group (ECOG) performance status (PS) score is 0-1

Exclusion Criteria:

• Patients who cannot understand the content of the experiment and cannot cooperate, and those who refuse to sign the informed consent form
• Small cell lung cancer
• Driver gene positivity
• Tumor directly invades esophagus, heart, aorta, diaphragm, trachea, or carina, or is considered unresectable even following induction therapy
• Patients with solid organ or blood system transplantation
• Previous use of recombinant cytotoxic T-lymphocyte associated antigen 4 (CTLA-4), programmed cell death 1 (PD-1), or programmed cell death ligand 1 (PD-L1) immune checkpoint inhibitors
• Patients with interstitial lung disease
• Patients with acute or chronic infectious disease
• Pregnant and lactating women
• Patients who have undergone other clinical drug trials

Potentially resectable stage IIIB-C driver-negative NSCLC patients receiving induction chemoimmunotherapy