Clinical trial · Observational
ctDNA Mutations and Methylation Status for Early Detection of Lung Cancer in Patients With Suspicious Lung Nodules
Circulating Tumor DNA Mutations and Methylation Status as Biomarkers for Early Detection of Lung Cancer in Patients With Suspicious Lung Nodules
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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
Conditions (3)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Lung Cancer Screening | — | UNRESOLVED | — |
| Lung Nodules | — | UNRESOLVED | — |
| Suspected Lung Cancer | — | UNRESOLVED | — |
Interventions
Interventions (2)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| ctDNA mutations and methylation with SPOTMAS Lung assays | Genetic | — | UNRESOLVED |
| Non-contrast LDCT Thorax scans | Radiation | — | UNRESOLVED |
Design
Arms and outcomes
Arms (0)
[]Primary outcomes (1)
- measure
- ctDNA mutation and methylation may contribute to the early identification of lung cancer in patients with suspicious lung nodules.
- timeFrame
- 2 year study follow up and surveillance
- description
- The presence of ctDNA mutation and methylation features in relation to the diagnosis or persistence of suspicious lung nodules
Secondary outcomes (1)
- measure
- 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
- timeFrame
- 2 year study follow up and surveillance
- description
- 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.
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 45 Years
- Maximum age
- 80 Years
Show eligibility criteria text
Inclusion Criteria: 1. Age 45 - 80 years; 2. 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 Exclusion Criteria: 1. Age \< 45 or \> 80; 2. Lung nodules of \< 0.5 cm in longest diameter, or with calcification seen in imaging; 3. Known lung cancer or lung metastasis before, or history of extra-pulmonary cancer; 4. Active tuberculosis; 5. Clinical unstable conditions including untreated ischemic heart disease or arrhythmia, uncontrolled airway disease; 6. Unwillingness to undergo invasive investigation like bronchoscopy; 7. Unable to provide informed written consent.
References
Publications (17)
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- BACKGROUNDTanner NT, Brasher PB, Jett J, Silvestri GA. Effect of a Rule-in Biomarker Test on Pulmonary Nodule Management: A Survey of Pulmonologists and Thoracic Surgeons. Clin Lung Cancer. 2020 Mar;21(2):e89-e98. doi: 10.1016/j.cllc.2019.05.004. Epub 2019 Jun 13. PMID 31732400
- BACKGROUNDFreiman MR, Clark JA, Slatore CG, Gould MK, Woloshin S, Schwartz LM, Wiener RS. Patients' Knowledge, Beliefs, and Distress Associated with Detection and Evaluation of Incidental Pulmonary Nodules for Cancer: Results from a Multicenter Survey. J Thorac Oncol. 2016 May;11(5):700-708. doi: 10.1016/j.jtho.2016.01.018. Epub 2016 Mar 7. PMID 26961390
- BACKGROUNDNguyen VTC, Vo DH, Tran TT, Tran TT, Nguyen THH, Vo TDH, Van TTV, Vu TL, Lam MQ, Nguyen GTH, Tran TH, Pham NT, Trac QT, Nguyen TH, Phan TV, Dao TH, Nguyen HTP, Nguyen LHD, Nguyen DS, Tang HS, Giang H, Phan MD, Nguyen HN, Tran LS. Cost-effective shallow genome-wide sequencing for profiling plasma cfDNA signatures to enhance lung cancer detection. Future Oncol. 2025 May;21(11):1391-1402. doi: 10.1080/14796694.2025.2483154. Epub 2025 Mar 25. PMID 40133038
- BACKGROUNDNguyen VTC, Nguyen TH, Doan NNT, Pham TMQ, Nguyen GTH, Nguyen TD, Tran TTT, Vo DL, Phan TH, Jasmine TX, Nguyen VC, Nguyen HT, Nguyen TV, Nguyen THH, Huynh LAK, Tran TH, Dang QT, Doan TN, Tran AM, Nguyen VH, Nguyen VTA, Ho LMQ, Tran QD, Pham TTT, Ho TD, Nguyen BT, Nguyen TNV, Nguyen TD, Phu DTB, Phan BHH, Vo TL, Nai THT, Tran TT, Truong MH, Tran NC, Le TK, Tran THT, Duong ML, Bach HPT, Kim VV, Pham TA, Tran DH, Le TNA, Pham TVN, Le MT, Vo DH, Tran TMT, Nguyen MN, Van TTV, Nguyen AN, Tran TT, Tran VU, Le MP, Do TT, Phan TV, Nguyen HL, Nguyen DS, Cao VT, Do TT, Truong DK, Tang HS, Giang H, Nguyen HN, Phan MD, Tran LS. Multimodal analysis of methylomics and fragmentomics in plasma cell-free DNA for multi-cancer early detection and localization. Elife. 2023 Oct 11;12:RP89083. doi: 10.7554/eLife.89083.