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.
Provision of informed consent prior to study initiation.
Age between 18 and 75 years.
Preoperative clinical evaluation indicating non-small cell lung cancer (NSCLC) stage I-IIIB (without initial treatment sought).
Newly treated patients who have consented to undergo surgery.
Non-small cell lung cancer (NSCLC) histopathologically determined to be other than stage I-IIIB following surgical evaluation.
Presence of other active malignant tumor diseases.
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.
History of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis requiring steroid therapy, or any indication of clinically active ILD.
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.
Cohort
Prospective
Blood ctDNA + methylation + PET-CT and Postoperative pathology
Procedure/SurgeryA 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) and Invasive mediastinoscopy /EBUS-TBNA
Procedure/SurgeryA 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).
Intraoperative lymph node dissection
Procedure/SurgeryFor 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.
Negative prediction value (NPV) of lymph node metastasis rates
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.
Disease-free survival (DFS)
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.
ctDNA-free interval (CFI)
CFI is defined as the duration between a patient's transition from ctDNA negative to ctDNA positive status.
Overall Survival (OS)
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.
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