ctDNA Mutations and Methylation Status for Early Detection of Lung Cancer in Patients With Suspicious Lung Nodules

NCT07615556 | Not Yet Recruiting

• 1 other identifier: HKU_UW_25_481
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 1

Brief 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

Suspected Lung Cancer; Lung Nodules; Lung Cancer Screening

Keywords

ctDNA mutation; Methylation status; Early detection of lung cancer; Suspicious lung nodules

Outcome Measures

Primary Outcomes (1)

• ctDNA mutation and methylation may contribute to the early identification of lung cancer in patients with suspicious lung nodules.

  The presence of ctDNA mutation and methylation features in relation to the diagnosis or persistence of suspicious lung nodules

  2 year study follow up and surveillance

Secondary Outcomes (1)

• Improving the accuracy of LDCT practices and supporting the identification of individuals who may benefit from further intervention at appropriate times Tumor surveillance could potentially impact costs and morbidities related to unnecessary intervention

  2 year study follow up and surveillance

Interventions

Non-contrast LDCT Thorax scans RADIATION

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.

ctDNA mutations and methylation with SPOTMAS Lung assays GENETIC

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.

Eligibility Criteria

• Age: 45 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

People with suspicious lung nodules on CT Thorax

You may qualify if:

• Age 45 - 80 years;
• Suspicious lung nodules (\> 0.5 - 30mm in longest diameter, non-calcified) found within the past six months, or if PET scan has been done before, the specific uptake value (SUV) should be more than 1

You may not qualify if:

• Age \< 45 or \> 80;
• Lung nodules of \< 0.5 cm in longest diameter, or with calcification seen in imaging;
• Known lung cancer or lung metastasis before, or history of extra-pulmonary cancer;
• Active tuberculosis;
• Clinical unstable conditions including untreated ischemic heart disease or arrhythmia, uncontrolled airway disease;
• Unwillingness to undergo invasive investigation like bronchoscopy;
• Unable to provide informed written consent.

Sponsors & Collaborators

• The University of Hong Kong: lead
• Bach Mai Hospital: collaborator
• Asian Pacific Society of Respirology: collaborator
• Tam Anh TP. Ho Chi Minh General Hospital: collaborator

Study Sites (1)

University of Hong Kong Queen Mary Hospital

Hong Kong, Hong Kong

Location

Related Publications (17)

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  BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Blood samples

MeSH Terms

Interventions

Methylation

Intervention Hierarchy (Ancestors)

Alkylation; Biochemical Phenomena; Chemical Phenomena; Organic Chemistry Phenomena; Metabolism

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 2 Years
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: May 22, 2026
• First Posted: May 29, 2026
• Study Start: June 1, 2026
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: June 8, 2026

Record last verified: 2026-06

Locations

HK (1)