Clinical trial NCT06358222: 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
Official title: Predicting NSCLC Lymph Node Metastasis: Integrating ctDNA Mutation/ Methylation Profiling With PET-CT Scan: The LUNon-invasive Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Carcinoma
Non-small Cell Lung Cancer
Keywords: Non-small Cell Lung Cancer
ctDNA
PET-CT
methylation
lymph node metastasis
Lead sponsor: Shanghai Chest Hospital
Sponsor class: OTHER
First posted: 2024-04-10
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

Brief summary: 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.

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).

Eligibility criteria: 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.

Primary outcomes:
measure: Negative prediction value (NPV) of lymph node metastasis rates
timeFrame: one day for each patient
measure: Disease-free survival (DFS)
timeFrame: Until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years.
measure: ctDNA-free interval (CFI)
timeFrame: Until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years.
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: Until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years
Other outcomes:
Locations:
city: ShangHai
country: China
facility: Shanghai Chest Hospital
Study officials:
References:
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