Liquid Biopsy in Advanced Oligometastatic NSCLC Receiving Surgery

Study Overview
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Brief Summary
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A prospective, observational study that assesses the clinical feasibility of ctDNA-based liquid biopsy in patients with oligometastatic NSCLC receiving surgery.

Detailed Description
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60 eligible patients will be enrolled. Dynamic blood samples before and after surgery and tissue samples will be obtained for exploratory analysis.

Official Title
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Liquid Biopsy in Advanced Oligometastatic NSCLC Receiving Surgery

Conditions
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Non-small Cell Lung Cancer, Oligometastatic Disease

Intervention / Treatment
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* Genetic: ctDNA testing and whole exome sequencing


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent must be obtained from patients and ability for patients to comply with the requirements of the study； Patients must be a man or woman of more than 18 years; ECOG PS ≦1； The function of the organs was evaluated by the surgeon to tolerate local surgical treatment； The classification was evaluated as simultaneous oligometastases at initial treatment or oligoresidual/oligoprogression/oligorecurrence after induction therapy; [Define: Initial treatment of simultaneous oligometastases: without systemic treatment, at the time of diagnosis, up to 5 metastases and up to 3 organs were involved, excluding pleural metastases or myeloid metastases. Oligoresidual after induction therapy: after systemic therapy, distant metastases were stable or reduced, primary lesions were stable or reduced, PET/CT metabolism was reduced, and no more than 5 residual lesions and no more than 3 organs were involved. Oligoprogression after induction therapy: After systemic therapy, some lesions were stable or reduced, while some original lesions were larger than before. Oligorelapses after induction therapy: after systemic therapy, systemic lesions were stable or reduced, and new local lesions appeared.] Lesion evaluation can be surgically removed. [Definition of operable resection: the lesion is limited and can be completely removed through surgery as assessed by the surgeon, with no significant impact on postoperative quality of life. Pulmonary surgical procedures include lobectomy, segmental resection and wedge resection. Pneumonectomy is not included.] Exclusion Criteria: Patients with a confirmed or suspected autoimmune disease; Patients with a history of human immunodeficiency virus (HIV) positive or acquired immunodeficiency syndrome (AIDS); Patients with a history of any arterial thrombosis within 6 months and history of deep vein thrombosis, pulmonary embolism, or any other severe thromboembolism within 3 months; Patients with any unstable systemic disease (eg, active infection, high-risk hypertension, unstable angina, congestive heart failure, etc.); Patients with a history of other malignancies in the past 5 years; Patients identified by the investigators patients with contraindications to local treatment; Patients with serious mental illness; Patients who cannot sign informed consent; Patients who cannot be followed up as scheduled;

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| oligometastatic disease<br>Dynamic blood samples before and after surgery and tissue samples from oligometastatic NSCLC undergone surgery will be obtained for exploratory analysis. | Genetic: ctDNA testing and whole exome sequencing<br>* Blood samples will be obtained for ctDNA testing and tumor tissue for whole exome sequencing.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Association between perioperative ctDNA-MRD characteristics and rogression-free survival | To explore the potential association among perioperative ctDNA-MRD characteristics and rogression-free survival within 2 years. | 2-year PFS | 
| Construction of a survival-prediction model | The survival-prediction model based on clinicopathological and genomic characteristics. | Through study completion, up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Association among ctDNA status before surgery, systemic treatment times, and survival | To explore the potential association among plasma ctDNA status surgery, systemic treatment time duration, PFS and OS. | Through study completion, up to 5 years | 
| Genomic characteristics and clonal evolution after systemic treatment | Using whole-exome sequencing to identify genomic characteristics and clonal evolution after systemic treatment | Through study completion, up to 5 years | 
| Potential drug-resistance mechanism identified by plasma ctDNA | Using plasma ctDNA-MRD to identify the potential drug-resistance mechanism. | Through study completion, up to 5 years | 
| Assess whether ctDNA-MRD is associated with radiological and pathological response after systematic therapy before surgery | Association among perioperative ctDNA-MRD characteristics, imaging response, and pathological response. | 60 patients underwent surgery | 
| Heterogeneity in Genomic and transcriptome between primary and metastatic tumors | Using whole-exome sequencing and whole transcriptome sequencing to identify genomic and transcriptome heterogeneity between primary and metastatic tumors. | 60 patients underwent surgery |