Circulating Tumor DNA Mutations and Methylation Status as Biomarkers for Early Detection of Lung Cancer in Patients With Suspicious Lung Nodules

Summary

Lung Cancer is common in Asia and is different from lung cancer from Western countries in terms of lung cancer epidemiology and management. Lung cancer can be detected early but most early stage lung cancer appear as lung nodules with suspicious features on imaging. Workup and surveillance for subjects with suspicious lung nodule is a clinical problem. There is no consensus and clinical practice usually varies with local epidemiology of lung diseases namely the local clinical characteristics especially with lung cancer and pulmonary tuberculosis. The clinical challenge is to address whether pulmonary nodules identified on CT screening carry short- and long-term risk for lung cancer.

The main objective of this study is to test the improvement of efficiency of diagnostic evaluation with clinical parameters and ctDNA mutation/methylation profiling for artificial intelligence modeling of for early detection of lung cancer in subjects with suspicious lung nodules.

The hypothesis is that ctDNA mutation and methylation will enhance early detection of lung cancer in patients with suspicious lung nodules.

This is a longitudinal cohort study. A total of 200 subjects (100 from Hong Kong and 100 from Vietnam) with suspicious lung nodules on CT Thorax will be recruited. Blood samples will be collected at recruitment and subsequent 6 months follow up. ctDNA mutations and methylation with SPOTMAS Lung assays would be performed at baseline and at 6 months follow up. The CT scan where the suspicious lung nodules were identified, will be used as baseline scan for recruitment. Recruited subjects will be arranged with a non-contrast LDCT scans at 6 months follow up.

The primary outcome measure of the study is the detection of ctDNA mutation and methylation in correlation with diagnosis of lung cancer or persistence of suspicious lung nodules. The secondary outcome measures of the study are the Sensitivity and specificity of clinical biomarkers in correctly identifying malignant lung nodule, i.e. lung cancer.

Conditions

• Suspicious Lung Nodules (> 0.5 - 30mm in Longest Diameter, Non-calcified)
• Suspicious Lung Nodules, With SUV More Than 1
• Early Detection of Lung Cancer

Interventions

GENETIC

ctDNA mutations and methylation with SPOTMAS Lung assays

Blood samples (25 ml) will be collected at recruitment and subsequent 6 months follow up. ctDNA mutations and methylation with SPOTMAS Lung assays would be performed at baseline and at 6 months follow up.

RADIATION

Non-contrast LDCT Thorax scans

Non-contrast LDCT scans will be done at 6 months follow up. LDCT Thorax scans will be performed on multi-detector (≥16 row) machines with minimum section collimation of ≤1 mm from lung apices to the adrenals. Low radiation dose acquisitions (≤1.5 mSv effective dose) are obtained using reduced mA and a minimum gantry rotation time.

Sponsors & Collaborators

• Tam Anh TP. Ho Chi Minh General Hospital

  collaborator OTHER

• Bach Mai Hospital

  collaborator OTHER

• Asian Pacific Society of Respirology

  collaborator UNKNOWN

• The University of Hong Kong

  lead OTHER

Eligibility

Min Age

45 Years

Max Age

80 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-06-30

Primary Completion

2028-06-30

Completion

2028-12-31

Countries

• Hong Kong

Study Locations