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.
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
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;
People with suspicious lung nodules on CT Thorax
Cohort
Prospective
ctDNA mutations and methylation with SPOTMAS Lung assays
GeneticBlood 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.
Non-contrast LDCT Thorax scans
RadiationNon-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 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
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
The performance characteristics of clinical biomarkers, including sensitivity and specificity, in differentiating malignant from non-malignant lung nodules, i.e. lung cancer. The area under the summary receiver operating characteristic curve (AUC) and diagnostic odds ratio (DOR) with the ctDNA assay. Potential improvement in positive diagnostic likelihood ratio (DLR+) and negative diagnostic likelihood ratio (DLR-) of using the in diagnosing lung cancer. An assessment of the cost-effectiveness of incorporating a clinical biomarker panel to enhance risk stratification of lung nodules and support diagnosis of lung cancer, expressed as the incremental cost per additional lung cancer diagnosed.
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The University of Hong Kong
Lead sponsor
Tam Anh TP. Ho Chi Minh General Hospital
Collaborator
Bach Mai Hospital
Collaborator
Asian Pacific Society of Respirology
Collaborator
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