To evaluate the predictive value of ctDNA in response, relapse for patients treated with immune checkpoint inhibitors or targeted therapy for ALK, ROS1, MET ex14 skipping.

In the study, 250 advanced NSCLC patients will be recruited. All the patients will receive tissue biopsy and circultating tumor DNA (ctDNA) liquid biopsy before entry the study. Patients who have no actionable mutations in EGFR or ALK and receive ICIs treatment and patients who carry actionable ROS1 fusion, ALK fusion or MET exon 14 skipping mutation and receive TKI treatment according to guidelines will take liquid biopsy assay to monitor the mutation status. The study will be ended when over 70% of the patients had a progressive disease (PD) in their targeted lesion.

Inclusion Criteria:

• Provision of informed consent
• Newly diagnosed and histological or cytological confirmed stage IIIB-IV lung adenocarcinoma or squamous cell carcinoma patients according to the AJCC staging system. The stage IV lung cancer and brain metastasis can be diagnosed by imaging and enhanced CT respectively
• No EGFR mutation in tissue and ctDNA
• Received immune checkpoint inhibitors as the first line therapy
• ECOG performance status 0-2 with expected more than 6 months of survival time
• Willingness to comply with required protocols and give permission to use the data for clinical research and products development

Exclusion Criteria:

• Patients have other primary cancers
• Patients have symptomatic brain metastasis, complications that are associated with brain metastasis or cognitive disorders
• Patients failed in either plasma or tissue sample QC

treatment naïve Stage IIIB or Stage IV NSCLC patients, adenocarcinoma or squamous cell carcinoma