A Prospective, Single-Center Observational Study Evaluating Recurrence Risk Using ctDNA-Based Molecular Residual Disease Monitoring in Patients With Gastric or Gastroesophageal Junction Adenocarcinoma Achieving Pathological Complete Response or Major Pathological Response After Neoadjuvant Therapy
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 150
- 试验地点
- 1
- 主要终点
- Three-Year Disease-Free Survival Rate
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
- •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.
研究组 & 干预措施
Prospective pCR/MPR Cohort
Participants with gastric or gastroesophageal junction adenocarcinoma who achieve pathological complete response or major pathological response after neoadjuvant therapy and R0 gastrectomy. All participants undergo longitudinal ctDNA-MRD monitoring and receive clinician-selected standard-of-care postoperative management.
干预措施: Tumor-Informed ctDNA-MRD Monitoring (Diagnostic Test)
Prospective pCR/MPR Cohort
Participants with gastric or gastroesophageal junction adenocarcinoma who achieve pathological complete response or major pathological response after neoadjuvant therapy and R0 gastrectomy. All participants undergo longitudinal ctDNA-MRD monitoring and receive clinician-selected standard-of-care postoperative management.
干预措施: Clinician-Selected Standard-of-Care Postoperative Treatment (Other)
结局指标
主要结局
Three-Year Disease-Free Survival Rate
时间窗: 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.
次要结局
- Three-Year Overall Survival Rate(From R0 gastrectomy through 3 years after surgery)
- Lead Time From ctDNA-MRD Detection to Radiographic Recurrence(From the first postoperative ctDNA-MRD assessment through 3 years after surgery)
- Sensitivity and Specificity of ctDNA-MRD for Postoperative Recurrence(From the first postoperative ctDNA-MRD assessment through 3 years after surgery)
- Three-Year Disease-Free Survival by Postoperative Adjuvant Treatment Strategy(From R0 gastrectomy through 3 years after surgery)
- Incidence of Adverse Events(From enrollment through 3 years after surgery)
研究者
Hao Xu
Principal Investigator and Chief Physician
The First Affiliated Hospital with Nanjing Medical University