Gastric Adenocarcinoma, Gastroesophageal Junction Adenocarcinoma
Conditions
Keywords
Circulating Tumor DNA, Molecular Residual Disease, Pathological Complete Response, Major Pathological Response, Neoadjuvant Therapy, Recurrence Risk
Brief summary
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.
Detailed description
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.
Interventions
DIAGNOSTIC_TESTTumor-Informed ctDNA-MRD Monitoring
Patient-specific somatic variants identified from tumor tissue are used to construct an individualized panel for ultra-deep sequencing of plasma cell-free DNA at prespecified perioperative and follow-up time points. Results are used for observational correlation and do not guide treatment changes.
OTHERClinician-Selected Standard-of-Care Postoperative Treatment
Postoperative treatment is selected by treating clinicians according to guidelines and individual clinical factors. The study does not assign, randomize, or modify treatment.
Sponsors
The First Affiliated Hospital with Nanjing Medical University
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Age 18 to 75 years. * Histologically confirmed gastric or gastroesophageal junction adenocarcinoma. * Completion of preoperative neoadjuvant therapy followed by R0 gastrectomy. * Postoperative pathological complete response, defined as Becker tumor regression grade 1a or Ryan tumor regression grade 0, or major pathological response, defined as Becker tumor regression grade 1b or Ryan tumor regression grade 1 with 10 percent or less residual viable tumor. * Willingness to undergo serial blood collection and follow-up and provision of written informed consent. * Eastern Cooperative Oncology Group performance status of 0 or 1 with adequate major organ function. * Adequate diagnostic biopsy or preoperative tumor tissue for 1021-gene panel testing.
Exclusion criteria
* Postoperative pathological assessment showing neither pathological complete response nor major pathological response, including more than 10 percent residual viable tumor or Becker tumor regression grade 2 to 3. * Distant metastatic disease identified intraoperatively or postoperatively. * Another malignant tumor within the previous 5 years. * Severe postoperative complications preventing any postoperative antitumor therapy. * Contraindication to immunotherapy, including active autoimmune disease.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Three-Year Disease-Free Survival Rate | From R0 gastrectomy through 3 years after surgery | Disease-free survival is defined as the time from R0 gastrectomy to the first documented tumor recurrence or death from any cause, whichever occurs first. Participants without an event will be censored at the last disease assessment. The 3-year disease-free survival rate will be estimated using the Kaplan-Meier method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Three-Year Overall Survival Rate | From R0 gastrectomy through 3 years after surgery | Overall survival is defined as the time from R0 gastrectomy to death from any cause. Participants alive at the last follow-up will be censored on that date. The 3-year overall survival rate will be estimated using the Kaplan-Meier method. |
| Lead Time From ctDNA-MRD Detection to Radiographic Recurrence | From the first postoperative ctDNA-MRD assessment through 3 years after surgery | Among participants with recurrence, lead time will be calculated as the interval in days between the first postoperative ctDNA-MRD-positive result and the first radiographically documented recurrence. Positive values indicate that ctDNA-MRD detection preceded radiographic recurrence. |
| Sensitivity and Specificity of ctDNA-MRD for Postoperative Recurrence | From the first postoperative ctDNA-MRD assessment through 3 years after surgery | Sensitivity and specificity of postoperative ctDNA-MRD status for detecting recurrence will be estimated using radiographic or clinically confirmed recurrence during follow-up as the reference standard. |
| Three-Year Disease-Free Survival by Postoperative Adjuvant Treatment Strategy | From R0 gastrectomy through 3 years after surgery | Among postoperative ctDNA-MRD-negative participants with pathological complete response or major pathological response, disease-free survival will be compared across clinician-selected standard-of-care postoperative adjuvant treatment strategies. Treatment is not assigned by the study. Analyses will account for measured baseline confounding using propensity score methods and multivariable models. |
| Incidence of Adverse Events | From enrollment through 3 years after surgery | The number and percentage of participants experiencing adverse events during routine postoperative treatment and follow-up will be summarized overall and by clinician-selected adjuvant treatment strategy. |
Countries
China
Contacts
CONTACTHao Xu
PRINCIPAL_INVESTIGATORHao Xu
The First Affiliated Hospital of Nanjing Medical University (Jiangsu Province Hospital)
Outcome results
None listed