Noninvasive Detection of Lung Nodule Malignancy Using cfDNA Fragmentomics

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.

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.