Diagnostic and Monitoring Significance of ctDNA Methylation Analysis by NGS in Benign and Malignant Pulmonary Nodules

Study Overview
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Brief Summary
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AnchorDx is using circulating tumor DNA (ctDNA) methylation analysis by next-generation sequencing (NGS) to develop a blood-based assay for differentiating benign and malignant pulmonary nodules early. The purpose of this study is to evaluate the diagnostic performance of this assay in patients with pulmonary nodules.

Detailed Description
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This is a prospective, multi-center, observational cohort study and seeks to enroll 10,560 participants with pulmonary nodules smaller than 3 cm in diameter from 21 hospitals in China. All participants will be followed up with chest CT or low-dose computed tomography (LDCT) scans for 2-3 years ( baseline, 3 months, 6 months, 12 months, 24 months and 36 months). Their blood samples, CT or LDCT scans data, and clinical data will be collected at each visit and Formalin-fixed paraffin-embedded (FFPE) tissues will be collected when participants who receive pneumonectomy or percutaneous lung biopsy.

Official Title
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Diagnostic and Monitoring Significance of Circulating Tumor DNA (ctDNA) Methylation Analysis by Next-Generation Sequencing in Benign and Malignant Pulmonary Nodules

Conditions
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Pulmonary Nodules

Intervention / Treatment
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* Diagnostic Test: ctDNA methylation analysis by NGS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 Years and older pulmonary nodules diagnosed by chest CT or low-dose computed tomography (LDCT) scans non-calcified pulmonary nodules with the diameter between 5mm to 30mm including solid nodules, mixed ground-glass opacity nodules and pure ground-glass opacity lung modules new cases of pulmonary nodules or diagnosed within 60 days prior to enrollment agree to finish the Patient Pulmonary History Questionnaire agree to be followed up for 2-3 years agree to provide a written informed consent Exclusion Criteria: pregnant or lactating women received any pneumonectomy or percutaneous lung biopsy before enrollment recipients of blood transfusions within 30 days prior to enrollment patients with tumors identified within 2 years prior to enrollment except non-melanoma skin cancer fail to understand or provide a written informed consent

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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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Prospective Cohort<br>This is a prospectively enrolling cohort study and a stratified case-cohort design will be employed to select malignant pulmonary nodules cases and benign pulmonary nodules subjects who will be assayed. All participants will be followed up with chest CT or low-dose computed tomography (LDCT) scans for 2-3 years, and take the diagnostic test, ctDNA methylation analysis by NGS, at each visit. | Diagnostic Test: ctDNA methylation analysis by NGS<br>* A blood-based assay for differentiating benign and malignant pulmonary nodules early using circulating tumor DNA (ctDNA) methylation analysis by next-generation sequencing (NGS)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The diagnostic performance of the blood-based assay for differentiating benign and malignant pulmonary nodules early using circulating tumor DNA (ctDNA) methylation analysis by next-generation sequencing (NGS) | The efficacy of the blood-based ctDNA methylation assay comparing with pathologic diagnosis, the gold standard, and CT/LDCT diagnosis, including sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). | 3 Years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The diagnostic and monitoring significance of routine tests integrating with ctDNA methylation analysis by NGS in differentiating benign and malignant pulmonary nodules | The diagnostic performance of the combination of routine tests and ctDNA methylation analysis by NGS in differentiating benign and malignant pulmonary nodules, including sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). | 3 Years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Circulating Tumor DNA (ctDNA), DNA Methylation Analysis, Next-Generation Sequencing (NGS), Low-Dose Computed Tomography (LDCT)