Diagnostic and Monitoring Significance of ctDNA Methylation Analysis by NGS in Benign and Malignant Pulmonary Nodules

Conditions

Pulmonary Nodules

Keywords

Circulating Tumor DNA (ctDNA), DNA Methylation Analysis, Next-Generation Sequencing (NGS), Low-Dose Computed Tomography (LDCT)

Brief summary

AnchorDx is using circulating tumor DNA (ctDNA) methylation analysis by next-generation sequencing (NGS) to develop a blood-based assay for differentiating benign and malignant pulmonary nodules early. The purpose of this study is to evaluate the diagnostic performance of this assay in patients with pulmonary nodules.

Detailed description

This is a prospective, multi-center, observational cohort study and seeks to enroll 10,560 participants with pulmonary nodules smaller than 3 cm in diameter from 21 hospitals in China. All participants will be followed up with chest CT or low-dose computed tomography (LDCT) scans for 2-3 years ( baseline, 3 months, 6 months, 12 months, 24 months and 36 months). Their blood samples, CT or LDCT scans data, and clinical data will be collected at each visit and Formalin-fixed paraffin-embedded (FFPE) tissues will be collected when participants who receive pneumonectomy or percutaneous lung biopsy.

Zeng F, Wang B, Peng M, Tao J, Tu X, Lu H, Qiu X, Yang Y, Wang W, Zeng M, Fan JB, Zeng Q, Liu Q.

2026-03-14

10.1007/s00330-026-12437-3

Prevalence and Epidemiological Characteristics of Incidental Pulmonary Nodules in China: A Prospective Multicenter Trial of 10,560 Cases

Wenhua Liang, Bo Wang, Jian Zhang, Dan Liu, Minhua Peng et al. (9 authors)

Epidemiology2023-09-09

10.1183/13993003.congress-2023.pa4435

Accurate classification of pulmonary nodules by a combined model of clinical, imaging, and cell-free DNA methylation biomarkers: a model development and external validation study.

He J, Wang B, Tao J, Liu Q, Peng M, Xiong S, Li J, Cheng B, Li C, Jiang S, Qiu X, Yang Y, Ye Z, Zeng F, Zhang J, Liu D, Li W, Chen Z, Zeng Q, Fan JB, Liang W.

2023-08-0947 citations

10.1016/s2589-7500(23)00125-5

A machine learning–based multidimensional model integrating clinical, radiomics, and cell-free DNA methylation biomarkers for the classification of pulmonary nodules.

Wenhua Liang, Bo Wang, Jinsheng Tao, Minhua Peng, Xixiang Tu et al. (11 authors)

Journal of Clinical Oncology2023-06-012 citations

10.1200/jco.2023.41.16_suppl.3070

Evaluating the diagnostic accuracy of a ctDNA methylation classifier for incidental lung nodules: protocol for a prospective, observational, and multicenter clinical trial of 10,560 cases

Wenhua Liang, Dan Liu, Min Li, Wei Wang, Qin Zheng et al. (39 authors)

Translational Lung Cancer Research2020-10-0112 citations

10.21037/tlcr-20-701

Interventions

DIAGNOSTIC_TESTctDNA methylation analysis by NGS

A blood-based assay for differentiating benign and malignant pulmonary nodules early using circulating tumor DNA (ctDNA) methylation analysis by next-generation sequencing (NGS)

Study design

Observational model

COHORT

Time perspective

PROSPECTIVE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Yes

Inclusion criteria

* 18 Years and older * pulmonary nodules diagnosed by chest CT or low-dose computed tomography (LDCT) scans * non-calcified pulmonary nodules with the diameter between 5mm to 30mm * including solid nodules, mixed ground-glass opacity nodules and pure ground-glass opacity lung modules * new cases of pulmonary nodules or diagnosed within 60 days prior to enrollment * agree to finish the Patient Pulmonary History Questionnaire * agree to be followed up for 2-3 years * agree to provide a written informed consent

Exclusion criteria

* pregnant or lactating women * received any pneumonectomy or percutaneous lung biopsy before enrollment * recipients of blood transfusions within 30 days prior to enrollment * patients with tumors identified within 2 years prior to enrollment except non-melanoma skin cancer * fail to understand or provide a written informed consent

Design outcomes

Primary

Measure	Time frame	Description
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)	3 Years	The efficacy of the blood-based ctDNA methylation assay comparing with pathologic diagnosis, the gold standard, and CT/LDCT diagnosis, including sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV).

Secondary

Measure	Time frame	Description
The diagnostic and monitoring significance of routine tests integrating with ctDNA methylation analysis by NGS in differentiating benign and malignant pulmonary nodules	3 Years	The diagnostic performance of the combination of routine tests and ctDNA methylation analysis by NGS in differentiating benign and malignant pulmonary nodules, including sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV).

Countries

China

Outcome results

None listed