Noninvasive Detection of Lung Nodule Malignancy Using cfDNA Fragmentomics (SHC2408)

A Prospective Clinical Study Evaluating the Noninvasive Use of Circulating Cell-Free DNA Fragmentomics to Differentiate Benign and Malignant Lung Nodules, With Emphasis on Small Nodules.

The goal of this observational study is to learn if cfDNA fragmentomics can noninvasively diagnose whether lung nodules are benign or malignant in adults with imaging-detected lung nodules.

Study Overview

• Status: Recruiting
• Conditions: Lung Cancer (Diagnosis); Fragmentomics
• Intervention / Treatment: Other: This study did not include intervention between two cohorts

• Study Type: Observational
• Enrollment (Estimated): 240

Contacts and Locations

• Study Contact: Name: Xuan Wang; Phone Number: +8613524594847; Email: dst.ding@gmail.com

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200030
      • Recruiting
      • Shanghai Chest Hospital
      • Contact: Wang; Phone Number: +8613524594847; Email: dst.ding@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

This study will enroll adults (≥18 years old) with CT-detected pulmonary nodules of specified types and sizes, who are willing to undergo diagnostic confirmation and provide a peripheral blood sample prior to treatment. Participants must not have received cancer therapy within the last 3 months.

Description

Inclusion Criteria:

• Age ≥ 18 years;
• Positive for lung nodules on low-dose spiral CT (LDCT) meeting one of the following criteria:

Solid or part-solid nodules ≥ 5 mm and ≤ 20 mm; Pure ground-glass nodules ≥ 8 mm and ≤ 30 mm; In cases of multiple nodules, the largest nodule (by maximum diameter) must meet these criteria;

• Participants whose lung nodule status (benign or malignant) can be clinically confirmed;
• No cancer-directed therapy (e.g., chemotherapy, radiotherapy, immunotherapy, cell therapy) within the past 3 months;
• Able to provide a 5 mL peripheral blood sample prior to any treatment;
• Voluntary signing of informed consent after full explanation of the study.

Exclusion Criteria:

• Pregnant or breastfeeding;
• Current or past diagnosis (within the past 5 years) of malignant tumors (excluding patients with early-stage lung cancer who have undergone surgery but still have multiple evaluable nodules), or with severe heart disease, serious liver or kidney disorders, or significant bone marrow hematopoietic dysfunction;
• History of organ transplantation or blood transfusion within the past 3 months;
• History of seropositivity for human immunodeficiency virus (HIV);
• Any other condition deemed inappropriate for study participation by the investigators.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Training Cohort; A group of 160 adults with imaging-detected lung nodules who will each provide a blood sample for cfDNA fragmentomics analysis. Data from this cohort will be used to train the diagnostic algorithm, teaching it to recognize the cfDNA patterns that distinguish benign from malignant nodules.	Other: This study did not include intervention between two cohorts; This study did not include intervention between two cohorts
Validation Cohort; An independent set of 80 adults with similar imaging-detected lung nodules. These participants will undergo the same blood sampling and cfDNA analysis, and their confirmed diagnoses (benign or malignant) will be used to evaluate the algorithm's performance-measuring sensitivity, specificity, accuracy, and area under the ROC curve.	Other: This study did not include intervention between two cohorts; This study did not include intervention between two cohorts

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Area under the receiver operating characteristic curve (AUC-ROC) for the cfDNA fragmentomics-based diagnostic model distinguishing malignant from benign lung nodules.	1 year

Collaborators and Investigators

• Sponsor: Baohui Han

Study record dates

Study Major Dates

• Study Start (Actual): August 21, 2024
• Primary Completion (Estimated): August 21, 2026
• Study Completion (Estimated): August 21, 2026

Study Registration Dates

• First Submitted: August 10, 2025
• First Submitted That Met QC Criteria: February 8, 2026
• First Posted (Actual): February 10, 2026

Study Record Updates

• Last Update Posted (Actual): February 10, 2026
• Last Update Submitted That Met QC Criteria: February 8, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: cfDNA; Non-invasive; Fragmentomics; Lung Cancer(Diagnosis); Small Nodule
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Pathological Conditions, Signs and Symptoms; Lung Neoplasms; Disease
• Other Study ID Numbers: ShanghaiChest2408

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE

Drug and device information, study documents

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