Circulating Tumor DNA Methylation Test to Differentiate Benign and Malignant Pulmonary Nodules

Study Overview
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Brief Summary
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Current state-of-the-art lung cancer early screening utilizes low-dose CT scan to identify lung nodules smaller than 3 cm in diameter. However, it's still a clinical challenge to differentiate between malignant and benign nodules. In previous studies, the investigators had taken the approach of methylation profiling by high throughput bisulfite DNA sequencing in tissue samples to identify specific methylation signatures. The investigators had learned methylation patterns that differentiate malignant vs. benign lesions from tissue samples by in-depth data mining, and then used pattern matching to classify plasma samples. In this study, the investigators are going to validate the efficacy of ctDNA methylation test for diagnosing early lung cancer by comparing results of the pre-surgery ctDNA methylation test with the post-surgery pathology.

Detailed Description
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This is a prospective, multi-center, observational cohort study and seeks to enroll 1230 participants with pulmonary nodules 5-30mm in diameter. The assay analyzes the ctDNA methylation profiles of lung cancer-specific biomarkers non-invasively using whole blood specimens collected before invasive surgery. The performance characteristics(sensitivity and specificity) of the pre-surgery ctDNA methylation test for detection of early lung cancer is evaluated in comparison to post-surgery pathology.

Official Title
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Multi-centers Validation of a Circulating Tumor DNA Assay to Differentiate Benign and Malignant Pulmonary Nodules Via Targeted High-throughput DNA Methylation Sequencing

Conditions
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Pulmonary Nodule, Solitary

Intervention / Treatment
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* Diagnostic Test: Circulating Tumor DNA Methylation Test


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years old or above single pulmonary nodule found by CT scan. the diameter of the pulmonary nodule is between 5mm to 30mm. plan to accept pneumonectomy due to the pulmonary nodule. without any sign of lymphatic or distant metastasis. agree to sign informed consent. Exclusion Criteria: pregnant or lactating women. the diameter of the pulmonary nodule is more than 30mm there are 2 or more pulmonary nodules in one single patient. any sign of lymphatic or distant metastasis

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

| Intervention/Treatment |
| --- |
|Diagnostic Test: Circulating Tumor DNA Methylation Test|Methylation profiling by high-throughput bisulfite DNA sequencing in blood sample to differentiate benign and malignant pulmonary nodules|

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, including sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pulmonary Nodule, Solitary