A Prospective Study on Predicting Recurrence Risk of Postoperative High-risk Gastrointestinal Stromal Tumors in NED State Based on Minimal Residual Disease Detection Via Liquid Biopsy
试验速览
- 阶段
- 不适用
- 状态
- 暂停
- 入组人数
- 66
- 试验地点
- 1
- 主要终点
- Drug retreatment response rate
研究概览
简要总结
The goal of this single-center, prospective, observational cohort study is to learn whether tumor-informed minimal residual disease (MRD) testing in blood can predict recurrence in 66 patients with high-risk gastrointestinal stromal tumor (GIST) who are not currently receiving postoperative adjuvant therapy. The main questions it aims to answer are:
Can changes in MRD during follow-up predict tumor recurrence? How closely do MRD results agree with contrast-enhanced computed tomography (CT) findings, and can MRD identify recurrence earlier than CT? Can tumor genomic features, changes in MRD, and clinicopathological features be combined to develop a model for predicting recurrence risk? Participants will have their surgical tumor tissue analyzed, provide blood samples for MRD testing, and undergo regular clinical follow-up and contrast-enhanced CT examinations for 3 years. Participants may choose to receive and discuss their MRD results. This study will not assign or change treatment based on MRD results. Recurrence and treatment decisions will remain based on routine clinical assessment, primarily contrast-enhanced CT and multidisciplinary review.
详细描述
This is a single-center, prospective, single-cohort, non-interventional observational study. The prospective cohort will include 66 patients with high-risk gastrointestinal stromal tumor (GIST) who have undergone R0 resection of the primary tumor. Eligible patients will either have no plan to receive postoperative adjuvant therapy or meet protocol-defined eligibility criteria after discontinuing such therapy.
Baseline tumor tissue will undergo whole-exome sequencing (WES) and next-generation sequencing (NGS). Fifty patient-specific variants associated with tumor development, progression, and individualized treatment will be selected to construct a personalized testing module. Cell-free DNA from peripheral blood will be analyzed using unique molecular identifier-based ultra-deep targeted NGS at a sequencing depth of approximately 100,000×. MRD positivity is defined as the detection of at least two significant loci with P ≤ 0.005.
Baseline contrast-enhanced computed tomography (CT) will confirm no evidence of disease before enrollment. Contrast-enhanced CT will be repeated every 3 months during 3 years of follow-up. Magnetic resonance imaging or positron emission tomography-CT may be performed when needed. Two experienced radiologists will independently review the CT images. Disagreements will be adjudicated by a third radiologist. Imaging recurrence will be evaluated according to Response Evaluation Criteria in Solid Tumors version 1.1 and confirmed by a multidisciplinary team.
Blood-based MRD testing will be performed at baseline and at protocol-specified follow-up visits. The study will compare MRD results with CT-based recurrence assessments and evaluate the predictive performance of MRD. It will also estimate the interval between the first MRD signal of recurrence and CT-confirmed recurrence.
The study will not assign or modify treatment. Participants who choose to receive their MRD results will receive a standardized explanation that the results are investigational. MRD results cannot independently establish a diagnosis of recurrence or guide treatment decisions. Participants who initiate a tyrosine kinase inhibitor (TKI) before imaging-confirmed recurrence may remain in follow-up. The primary MRD performance analysis will include only MRD, imaging, and clinical data collected before TKI initiation. Post-TKI recurrence status will not be used to reclassify pre-TKI MRD results in the primary MRD performance analysis.
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
- •I. Inclusion Criteria for the Prospective Study on Postoperative Minimal Residual Disease (MRD) Surveillance in High-Risk Gastrointestinal Stromal Tumors (GIST) Without Adjuvant Therapy
- •Aged 18-75 years.
- •Patients suspected of having high-risk GIST based on preoperative imaging, or patients with biopsy-confirmed high-risk GIST who have not received preoperative neoadjuvant therapy.
- •Treatment-naive patients who have not previously received radiotherapy, chemotherapy, surgery, or any other anticancer treatment.
- •Adequate hepatic, renal, and other major organ function, with the patient considered medically fit to undergo surgery.
- •Postoperative pathological confirmation of gastrointestinal stromal tumor.
- •Tumor genotyping demonstrating a genotype associated with primary resistance to imatinib, such as a PDGFRA D842V mutation, or a clear decision by the patient to decline postoperative adjuvant imatinib therapy.
- •A definite contraindication to imatinib or another targeted therapy.
- •Patients who underwent R0 resection of the primary tumor, completed long-term postoperative adjuvant therapy, and discontinued treatment at least 3 months previously.
- •The patient and family members are able to understand the study protocol; the patient voluntarily agrees to participate and provides written informed consent.
- •II. Inclusion Criteria for the Development of a Genomics-Based Recurrence Risk Prediction Model for High-Risk GIST and Identification of the Optimal Target Population for MRD Surveillance a. The inclusion criteria are identical to those of the prospective study on postoperative MRD surveillance in high-risk GIST without adjuvant therapy.
排除标准
- •I. Exclusion Criteria for the Prospective Study on Postoperative Minimal Residual Disease (MRD) Surveillance in High-Risk Gastrointestinal Stromal Tumors (GIST) Without Adjuvant Therapy
- •A history of another malignant tumor or the presence of another concurrent malignancy.
- •Emergency surgery required because of intestinal obstruction, perforation, bleeding, or a similar condition.
- •Pregnancy or breastfeeding.
- •A history of severe psychiatric illness.
- •Any contraindication to surgical treatment.
- •Failure to achieve R0 resection.
- •Low- or intermediate-risk disease according to postoperative pathological risk stratification.
- •Presence of distant metastasis.
- •Any other condition that, in the investigator's judgment, renders the patient unsuitable for enrollment.
- •II. Exclusion Criteria for the Development of a Genomics-Based Recurrence Risk Prediction Model for High-Risk GIST and Identification of the Optimal Target Population for MRD Surveillance
- •a. The exclusion criteria are identical to those of the prospective study on postoperative MRD surveillance in high-risk GIST without adjuvant therapy.
研究组 & 干预措施
High-Risk GIST MRD Monitoring Cohort
Patients with high-risk gastrointestinal stromal tumor who have undergone R0 resection of the primary tumor and are not currently receiving postoperative adjuvant therapy will undergo serial blood-based ctDNA-MRD testing and routine imaging follow-up for 3 years. The study will not assign or modify treatment.
干预措施: Tumor-Informed ctDNA-Based MRD Testing (Diagnostic Test)
High-Risk GIST MRD Monitoring Cohort
Patients with high-risk gastrointestinal stromal tumor who have undergone R0 resection of the primary tumor and are not currently receiving postoperative adjuvant therapy will undergo serial blood-based ctDNA-MRD testing and routine imaging follow-up for 3 years. The study will not assign or modify treatment.
干预措施: Contrast-Enhanced CT (Diagnostic Test)
结局指标
主要结局
Drug retreatment response rate
时间窗: 3 years from the time when patients first enter the drug holiday
Drug response rate among patients who take drug re-use due to disease progression within 3 years after first entering drug holiday
Drug re-use rate
时间窗: 3 years from the time when patients first enter the drug holiday
The proportion of patients who take drug re-use due to disease progression within 3 years after first entering drug holiday
Progress-free Survival
时间窗: From date when patients first enter the drug holiday until the date of imaging examinations confirmed disease progression up to 3 years
Progression-free survival after patients first enter the drug holiday
Agreement Between MRD and Contrast-Enhanced CT Recurrence Assessments
时间窗: From baseline through 3 years of follow-up or until imaging-confirmed recurrence.
At each scheduled follow-up visit, agreement between MRD status (positive or negative) and recurrence status determined by contrast-enhanced CT and multidisciplinary review will be evaluated using Cohen's kappa coefficient with a 95% confidence interval.
Three-Year Recurrence Rate
时间窗: At the end of the 3-year follow-up.
The percentage of participants with local recurrence or distant metastasis confirmed by contrast-enhanced CT and multidisciplinary review during the 3-year follow-up period.
次要结局
- MRD versus imaging examination(3 years from the time when patients first enter the drug holiday)
- Overall Survival(From date when patients first enter the drug holiday until the date of death up to 3 years)
- genetic mutation profiling of ctDNA-MRD(3 years from the time when patients first enter the drug holiday)
- Predictive Performance of MRD for Imaging-Confirmed Recurrence(From baseline through the end of the 3-year follow-up.)
- Lead Time From MRD Positivity to CT-Confirmed Recurrence(During the 3-year follow-up, through the first CT-confirmed recurrence.)
- Recurrence-Free Survival(From the date of surgery through the end of the 3-year follow-up.)
- Overall Survival(From the date of surgery through the end of the 3-year follow-up.)
- Longitudinal Changes in ctDNA-MRD Genomic Features(At baseline and protocol-specified follow-up visits for up to 3 years.)
- MRD Positivity According to Clinicopathological and Genomic Factors(After completion of the 3-year follow-up and data collection.)
- Performance of the Recurrence-Risk Prediction Model(After completion of the 3-year follow-up and model development and validation.)
研究者
Zhidong Gao
Professor and Chief Physician, Department of Gastrointestinal Surgery
Peking University People's Hospital