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

Diagnostic and Monitoring Significance of Circulating Tumor DNA (ctDNA) Methylation Analysis by Next-Generation Sequencing in Benign and Malignant Pulmonary Nodules

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Pulmonary Nodules
• Intervention / Treatment: Diagnostic test: ctDNA methylation analysis by NGS

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.

• Study Type: Observational
• Enrollment (Actual): 10560

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • Department of Respiratory and Critical Care Medicine, Beijing Chaoyang Hospital
  • Changsha, China
    • Xiangya Hospital of Central South University
  • Chengdu, China
    • Department of Respiratory Medicine, West China Hospital of Sichuan University
  • Guangzhou, China
    • The First Affiliated Hospital of Guangzhou Medical University
  • Guangzhou, China
    • Department of Pulmonary Medicine, The First Affiliated Hospital of Sun Yat-Sen University
  • Guiyang, China
    • Department of Respiration and Critical Care Medicine, Guizhou Provincial People's Hospital
  • Hohhot, China
    • Department of Pulmonary and Critical Care Medicine, Inner Mongolia Autonomous Region People's Hospital
  • Jinan, China
    • Department of Respiratory, QILU Hospital, Shandong University
  • Kunming, China
    • Department of Respiratory Medicine, The First People's Hospital of Yunnan Province
  • Lanzhou, China
    • Department of Gerontal Respiratory Medicine, The Frist Hospital of Lanzhou University
  • Nanchang, China
    • Department of Respiration, The First Affiliated Hospital of Nanchang University
  • Shanghai, China
    • Department of Pulmonary & Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
  • Shanghai, China
    • Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University
  • Shanghai, China
    • Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University
  • Shanghai, China
    • Department of Respiratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine
  • Shantou, China
    • Department of Respiratory Medicine, Shantou Central Hospital
  • Shenyang, China
    • Department of Respiratory Medicine, The First Hospital of China Medical University
  • Shenzhen, China
    • Department of Respiratory Medicine, Shenzhen People's Hospital
  • Wuhan, China
    • Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology
  • Xi'an, China
    • Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital, Xi'an Jiaotong University
  • Xi'an, China
    • Department of Pulmonary Medicine, Xijing Hospital, Air Force Medical University of PLA
  • Xiamen, China
    • Department of Cardiothoracic Surgery, The Second Affiliated Hospital of Xiamen Medical College
  • Zhengzhou, China
    • Department of Respiratory Medicine, Henan Provincial People's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

Subjects with pulmonary nodules diagnosed by chest CT or low-dose computed tomography (LDCT) scans

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Prospective Cohort; This is a prospectively enrolling cohort study and a stratified case-cohort design will be employed to select malignant pulmonary nodules cases and benign pulmonary nodules subjects who will be assayed. All participants will be followed up with chest CT or low-dose computed tomography (LDCT) scans for 2-3 years, and take the diagnostic test, ctDNA methylation analysis by NGS, at each visit.

Diagnostic test: ctDNA 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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	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).	3 Years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The diagnostic and monitoring significance of routine tests integrating with ctDNA methylation analysis by NGS in differentiating benign and malignant pulmonary nodules	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).	3 Years

Collaborators and Investigators

• Sponsor: AnchorDx Medical Co., Ltd.
• Collaborators: The First Affiliated Hospital with Nanjing Medical University; The First Affiliated Hospital of Nanchang University; Xiangya Hospital of Central South University; LanZhou University; Shanghai Zhongshan Hospital; Peking University Third Hospital; First Affiliated Hospital, Sun Yat-Sen University; West China Hospital; Tongji Hospital; Qilu Hospital of Shandong University; First Affiliated Hospital Xi'an Jiaotong University; Beijing Chao Yang Hospital; The First Affiliated Hospital of Zhengzhou University; Guizhou Provincial People's Hospital; Shanghai Chest Hospital; The First Affiliated Hospital of Guangzhou Medical University; Shenzhen People's Hospital; Henan Provincial People's Hospital; First Hospital of China Medical University; Second Hospital of Jilin University; Inner Mongolia People's Hospital; The First People's Hospital of Yunnan; Shanghai Pulmonary Hospital affiliated to Tongji University; Shantou Affiliated Hospital of Sun Yat-Sen University; Ruijin Hospital, The Shanghai Jiao Tong University Medical School; Xijing Hospital, Air Force Medical University of PLA; Xiamen Second Hospital
• Investigators: Study Chair: Nanshan ZHONG, MD, The First Affiliated Hospital of Guangzhou Medical University

Publications and helpful links

General Publications

• Liang W, Liu D, Li M, Wang W, Qin Z, Zhang J, Zhang Y, Hu Y, Bao H, Xiang Y, Wang B, Wu J, Sun J, Hu C, Ye X, Zhang X, Xiao W, Yun C, Sun D, Wang W, Chang N, Zhang Y, Zhao J, Zhang X, Xu J, Wu D, Liu X, Guo Y, Zhang Q, Zhang W, Yang L, Li Z, Zhang X, Han B, Tong Z, He J, Qu J, Fan JB, Zhong N. 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. Transl Lung Cancer Res. 2020 Oct;9(5):2016-2026. doi: 10.21037/tlcr-20-701.

Study record dates

Study Major Dates

• Study Start (Actual): November 26, 2018
• Primary Completion (Anticipated): September 1, 2024
• Study Completion (Anticipated): June 1, 2025

Study Registration Dates

• First Submitted: August 27, 2018
• First Submitted That Met QC Criteria: August 27, 2018
• First Posted (Actual): August 29, 2018

Study Record Updates

• Last Update Posted (Actual): May 24, 2023
• Last Update Submitted That Met QC Criteria: May 23, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Circulating Tumor DNA (ctDNA); DNA Methylation Analysis; Next-Generation Sequencing (NGS); Low-Dose Computed Tomography (LDCT)
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Multiple Pulmonary Nodules
• Other Study ID Numbers: AnchorDx LC201801

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No