Tumor-informed MRD for Non-small Cell Lung Cancer

An Observational Study on the Prediction of Recurrence Risk in Early-stage Non-small Cell Lung Cancer Using a Customized MRD Monitoring Scheme Based on Tumor Tissue WES

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.

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.

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.