To evaluate the concordance of sensitizing mutations detected between paired plasma and tissue samples; the correlation between the clonal status of sensitizing mutations and targeted therapy response; and the prognostic impact of the relative abundance of sensitizing / resistance mutations.

In the study, 500 advanced NSCLC patients will be recruited. All the patients will receive biopsy genotype assay and circultating tumor DNA (ctDNA) liquid biopsy. Patients who carry actionable EGFR mutation, ROS1 fusion, ALK fusion or MET exon 14 skipping mutation will receive TKI treatment according to guidelines. During the TKI treatment, every patients will take liquid biopsy assay to monitor the mutation status. The study will be ended when all 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 non-smoking 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
• 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 without smoking history