Predicting Non-small Cell Lung Cancer (NSCLC) Lymph Node Metastasis: Integrating Circulating Tumor DNA (ctDNA) Mutation/ Methylation Profiling With Positron Emission Tomography-computed Tomography (PET-CT) Scan

May 14, 2025 updated by: Feng Yao, Shanghai Chest Hospital

Predicting NSCLC Lymph Node Metastasis: Integrating ctDNA Mutation/ Methylation Profiling With PET-CT Scan: The LUNon-invasive Study

This is a single center, prospective and observational study conducted in three stages to predict the NSCLC lymph node metastasis based on ctDNA/specific methylation molecular features combined with PET-CT imaging features and intervention study.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a prospective study conducted in three stages. The volume of blood drawn will be 30 mL each time.

Stage 1: We will enroll 200 patients diagnosed with stage I-IIIB NSCLC who are scheduled for lobectomy and systematic lymph node dissection. The prediction of lymph node metastasis will be based on preoperative blood ctDNA mutation and methylation profiling. Specifically, during this stage, we will prospectively establish ctDNA methylation signatures specifically associated with LNMs in NSCLC. These molecular profiles will be combined with PET-CT imaging. Postoperative pathological results will serve as the reference standard for comparison.

Stage 2: A certain number (depending on the Results of Stage 1) of patients requiring invasive mediastinoscopy or EBUS-TBNA, based on the clinical guidelines, will be included for blood ctDNA mutation/methylation profile (or combined PET-CT), and the detection rate of LNMs will be assessed in patients with negative preoperative blood ctDNA mutation/methylation (or combined PET-CT). The accuracy of predicting LNMs will be compared with that of patients with negative or positive preoperative blood ctDNA mutation/methylation (or combined PET-CT).

Stage 3: For patients with negative preoperative blood negative testing (ctDNA mutation/methylation profiles alone or in combination with PET-CT), systematic lymph node sampling/dissection and no lymph node dissection will be grouped and compared. Regular follow-up is performed to investigate the impact on long-term MRD negative duration and prognosis. The primary outcomes: postoperative MRD negative duration and progression-free survival (PFS); The second outcomes: Overall survival (OS).

Study Type

Observational

Enrollment (Estimated)

200

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
      • ShangHai, China
        • Recruiting
        • Shanghai Chest Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

This program will be conducted in three stages. Stage 1: We will enroll 200 patients diagnosed with stage I-IIIB NSCLC who are scheduled for lobectomy and systematic lymph node dissection.

Stage 2: A certain number (depending on the Results of Stage 1) of patients requiring invasive mediastinoscopy or EBUS-TBNA, based on the clinical guidelines, will be included for blood ctDNA mutation/methylation profile (or combined PET-CT), and the detection rate of LNMs will be assessed in patients with negative preoperative blood ctDNA mutation/methylation (or combined PET-CT).

Stage 3: For patients with negative preoperative blood negative testing (ctDNA mutation/methylation profiles alone or in combination with PET-CT), systematic lymph node sampling/dissection and no lymph node dissection will be grouped and compared.

Description

Inclusion Criteria:

  1. Provision of informed consent prior to study initiation.
  2. Age between 18 and 75 years.
  3. Preoperative clinical evaluation indicating non-small cell lung cancer (NSCLC) stage I-IIIB (without initial treatment sought).
  4. Newly treated patients who have consented to undergo surgery.
  5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0-1.

Exclusion Criteria:

  1. Non-small cell lung cancer (NSCLC) histopathologically determined to be other than stage I-IIIB following surgical evaluation.
  2. Presence of other active malignant tumor diseases.
  3. Evidence of any serious or uncontrolled systemic illness, including uncontrolled hypertension and active bleeding, as assessed by the investigator, which may contribute to reluctance to participate in the trial or decrease adherence to the study regimen. Additionally, active infectious diseases such as hepatitis B, hepatitis C, and human immunodeficiency virus (HIV) infection are grounds for exclusion.
  4. History of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis requiring steroid therapy, or any indication of clinically active ILD.
  5. Patients considered by the investigator to be unable to comply with the study protocol, restrictions, and requirements, or those facing circumstances at the investigator's discretion that would impede their participation in the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Blood ctDNA + methylation + PET-CT vs Postoperative pathology
Procedure: Blood ctDNA + methylation + PET-CT and Postoperative pathology
A highly sensitive tumor-naïve MRD panel of ctDNA will be employed to detect preoperative blood. Some patients will undergo methylation profiling to prospectively establish LNMs-specific ctDNA methylation signatures.
MRD+ methylation (or combined with PET-CT) vs Invasive mediastinoscopy /EBUS-TBNA
Procedure: MRD+ methylation (or combined with PET-CT) and Invasive mediastinoscopy /EBUS-TBNA
A certain number (depending on the Results of Stage 1) of patients requiring invasive mediastinoscopy or EBUS-TBNA, based on the clinical guidelines, will be included for blood ctDNA mutation/methylation profile (or combined PET-CT), and the detection rate of LNMs will be assessed in patients with negative preoperative blood ctDNA mutation/methylation (or combined PET-CT). The accuracy of predicting LNMs will be compared with that of patients with negative or positive preoperative blood ctDNA mutation/methylation (or combined PET-CT).
Lymph Node dissection vs no lymph node dissection
Procedure: Intraoperative lymph node dissection
For patients with negative preoperative blood negative testing (ctDNA mutation/methylation profiles alone or in combination with PET-CT), systematic lymph node sampling/dissection and no lymph node dissection will be grouped and compared. Regular follow-up is performed to investigate the impact on long-term MRD negative duration and prognosis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Negative prediction value (NPV) of lymph node metastasis rates
Time Frame: one day for each patient
The primary endpoint will be the negative prediction value (NPV) of LNM rates between groups using preoperative blood ctDNA/methylation alone or in combination with PET-CT. LNMs-specific ctDNA methylation signatures will be developed and the sensitivity and specificity of ctDNA mutation/methylation profiles alone or when combined with PET-CT scans for predicting LNMs will be assessed. Postoperative pathological results will serve as the reference standard for comparison.
one day for each patient
Disease-free survival (DFS)
Time Frame: Until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years.
DFS is defined as the time from surgical resection to tumor recurrence or death due to tumor progression. DFS will be compared between the ctDNA-positive group and the ctDNA-negative group. DFS will be assessed in stage 3.
Until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years.
ctDNA-free interval (CFI)
Time Frame: Until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years.
CFI is defined as the duration between a patient's transition from ctDNA negative to ctDNA positive status.
Until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival (OS)
Time Frame: Until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years
OS is defined as the time between the start of the patient's surgical resection and any documented death from any cause. OS will be compared between ctDNA-positive and ctDNA-negative groups. OS will be assessed in stage 3.
Until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Shanghai Chest Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 15, 2023

Primary Completion (Estimated)

December 31, 2027

Study Completion (Estimated)

December 31, 2027

Study Registration Dates

First Submitted

March 28, 2024

First Submitted That Met QC Criteria

April 6, 2024

First Posted (Actual)

April 10, 2024

Study Record Updates

Last Update Posted (Actual)

May 18, 2025

Last Update Submitted That Met QC Criteria

May 14, 2025

Last Verified

May 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • LUNon-invasive

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

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Carcinoma

Clinical Trials on Blood ctDNA + methylation + PET-CT and Postoperative pathology

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Peru

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe