Non-small Cell Lung Cancer (NSCLC)
Conditions
Keywords
non-small cell lung cancer, WES, MRD
Brief summary
The goal of this study is to evaluate the clinical utility of a personalized, WES-informed MRD detection approach in patients with early-stage non-small cell lung cancer, with a focus on its association with postoperative recurrence and prognosis, as well as its ability to predict recurrence earlier than imaging.
Detailed description
Background: Non-small cell lung cancer (NSCLC) is associated with a high risk of postoperative recurrence despite curative-intent surgery. Minimal residual disease (MRD) detection using circulating tumor DNA (ctDNA) has emerged as a promising approach for early identification of molecular relapse. Tumor-informed strategies based on whole-exome sequencing (WES) enable personalized MRD monitoring with improved sensitivity and specificity. Objective: To evaluate the clinical utility of a personalized, WES-informed MRD detection approach in patients with early-stage NSCLC, focusing on its association with postoperative recurrence and prognosis, its ability to predict recurrence earlier than imaging, and its role in assessing treatment efficacy. Methods: This is a single-center, prospective, observational study enrolling 450 patients with newly diagnosed stage IIB-III NSCLC undergoing surgical treatment. Tumor tissue and matched blood samples will undergo WES to identify patient-specific somatic mutations for the development of individualized MRD panels. Serial plasma samples will be collected at predefined time points before and after surgery, during neoadjuvant/adjuvant therapy, and throughout follow-up. MRD status will be dynamically monitored using ctDNA analysis. Endpoints: The primary endpoint is recurrence-free survival (RFS). Secondary endpoints include lead time between MRD detection and imaging-confirmed recurrenceand correlation between MRD status and treatment outcomes.
Interventions
None listed
Sponsors
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Histologically or cytologically confirmed non-small cell lung cancer (NSCLC); 2. Newly diagnosed patients who are planned to undergo surgical treatment; 3. Age ≥18 years, regardless of sex; 4. Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0-1; 5. Written informed consent must be obtained prior to any study-related procedures, sampling, or analyses; patients must be able to provide sufficient tissue and/or blood samples required for the study, with tumor cell content ≥20% as confirmed by pathological assessment; 6. Ability to comply with study requirements, including assessment of treatment efficacy, adverse events, and prognosis; 7. Willingness to undergo next-generation sequencing (NGS) testing.
Exclusion criteria
1. Patients unwilling to provide tissue and blood samples for genetic testing; 2. Patients who are mentally or medically unstable, rendering them unable or unwilling to provide written informed consent; 3. Patients deemed by the investigator to be unsuitable for participation in the study, or those with poor compliance with study procedures, restrictions, and requirements.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| RFS is determined as the duration from the date of surgery to the date of first detected disease recurrence or metastasis or death from any cause, whichever occurs first. | From enrollment to the end of follow up at 3 years |
Secondary
| Measure | Time frame |
|---|---|
| "Leading time" is defined as the time interval by which tumor recurrence detected by MRD precedes recurrence detected by imaging （CT/MRI/PET-CT ）. | From enrollment to the end of follow up at 3 years |
| OS is determined as the time from treatment to death. | From enrollment to the end of follow up at 3 years |
Countries
China
Contacts
PRINCIPAL_INVESTIGATORWang Minghui
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Outcome results
None listed