Evolution of Multiple Primary Lung Cancer (Evolution)

Study Overview
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Brief Summary
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To investigate the evolutionary genomic landscape, explore the genetic tumor heterogeneity and microenvironment of multiple primary lung cancer (MPLC) by using tissue genetic analysis and circulating tumor DNA detection, in order to provide robust evidence for the diagnosis, treatment, and surveillance of MPLC.

Detailed Description
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Multiple primary lung cancer (MPLC) has become a worldwide problem due to the difficulty in diagnosis, treatment and surveillance. Although exploring tumour clonal heterogeneity and microenvironment can help understand cancer evolution and impact therapeutic outcome, study is still lacking in this field on MPLC. Circulating tumor DNA (ctDNA) are short DNA fragments, which can be obtained conveniently and non-invasively, providing comprehensive views of the tumor as were shed by tumor cells from multiple tumor regions. Therefore, we design a prospective study of patients with surgically treated MPLC, aiming to use ctDNA technique to define the evolutionary landscape of MPLC through inter-tumor and intra-tumor heterogeneity by multi-region sampling and genetic analysis. We will also explore the the microenvironment by RNA sequencing and T cell receptor sequencing. This study may help understand the genetic evolution and microenvironment of MPLC, and provide evidence for the diagnosis, treatment and surveillance of these patients.

Official Title
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The Genetic Evolution and Microenvironment of Multiple Primary Lung Cancer

Conditions
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Multiple Primary Lung Cancers, Lung Cancer, Non Small Cell Lung Cancer

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 18 to 80 years Patients who are clinically diagnosed multiple lung cancers, and undergo surgical treatment. No history of any malignancy in recent 5 years. No chemotherapy, radiotherapy or targeted therapy will be performed before surgery. Surgical removal of at least 2 tumors confirmed to be lung cancer postoperatively by pathologic evaluation. Exclusion Criteria: All lesions present as pure ground-glass opacities (GGOs) on CT scans. Patients who do not undergo R0 resection (including tumors located bilaterally but only unilaterally resected). Unqualified blood samples. Unable to comply with the study procedure

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor heterogeneity of multiple primary lung cancer | Explore the intra-tumor and inter-tumor genetic heterogeneity by analysis of clonal and subclonal mutations detected by ctDNA. | 3 year | 
| Microenvironment of multiple primary lung cancer | Using RNA sequencing and T cell receptor (TCR) sequencing to evaluate the microenvironment of each lesion of multiple primary lung cancer, including T cell receptpr clonality ,diversity , evenness, and richness. | 3 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation between ctDNA and clonal variation | Explore the correlation between the detection rate of ctDNA and subclonal mutations of different tumor sites detected by genetic analysis. | 3 year | 
| Correlation between ctDNA and tumor burden | Explore the correlation between the detection rate of ctDNA and tumor burden. | 3 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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evolution, multiple primary lung cancer, ctDNA, tumor heterogeneity, microenvironment