ctDNA-MRD Monitoring After Neoadjuvant Therapy in Gastric Cancer With pCR or MPR

Overview

This prospective observational study will enroll adults with gastric or gastroesophageal junction adenocarcinoma who achieve pathological complete response or major pathological response after neoadjuvant therapy and R0 gastrectomy. The study will evaluate whether postoperative circulating tumor DNA-based molecular residual disease status can identify participants at increased risk of recurrence despite a favorable pathological response. All postoperative treatment decisions will be made by the treating clinicians according to routine care and will not be assigned by the study. Tumor-informed ctDNA-MRD testing will be performed longitudinally, and results will not be used to alter treatment. Participants will be followed for disease-free survival, overall survival, recurrence detection, and adverse events.

This is a prospective, single-center, noninterventional real-world cohort study in participants with locally advanced gastric or gastroesophageal junction adenocarcinoma who have completed neoadjuvant therapy, undergone R0 gastrectomy, and achieved pathological complete response or major pathological response. The primary objective is to assess the prognostic stratification value of postoperative ctDNA-based molecular residual disease status. Secondary objectives are to compare disease-free survival across clinician-selected postoperative adjuvant treatment strategies among ctDNA-MRD-negative participants, evaluate the diagnostic performance and lead time of ctDNA-MRD monitoring for recurrence, and describe adverse events associated with routine postoperative treatment. The tumor-informed ctDNA-MRD assay will use somatic variants identified from diagnostic biopsy or resection tissue to construct an individualized monitoring panel. Plasma cell-free DNA will undergo ultra-deep sequencing with molecular error correction. A negative result is defined as no stable detection of tumor-derived variants at an allele frequency of 0.02 percent or higher in a quality-controlled sample with adequate cell-free DNA input. Blood is planned before surgery, approximately 1 month after surgery before adjuvant treatment, approximately 3 months after surgery or after completion of adjuvant chemotherapy, and subsequently every 3 to 6 months when feasible. ctDNA-MRD results are intended for correlative analysis and will not direct changes in clinical treatment. Postoperative adjuvant therapy will be selected by treating clinicians according to applicable guidelines, pathological and molecular features, treatment tolerance, multidisciplinary discussion, participant preference, and financial considerations. The study will not randomize participants or assign therapy. Imaging and survival follow-up will occur every 3 months during the first postoperative year and every 3 to 6 months thereafter through 3 years after surgery or until recurrence or death. Analyses will include Kaplan-Meier estimates, Cox proportional hazards models, and propensity score methods to address measured confounding in comparisons of treatment strategies.