Circulating Tumor DNA Methylation Guided Postoperative Follow-up Strategy for Non-metastatic Colorectal Cancer
- Conditions
- Non-metastatic Colorectal CancerCirculating Tumor DNA Methylation
- Interventions
- Diagnostic Test: ctDNA methylation dynamic monitoring
- Registration Number
- NCT05904665
- Lead Sponsor
- Fudan University
- Brief Summary
Colorectal cancer (CRC) is one of the most common gastrointestinal tumors. According to the latest cancer report, the incidence and mortality rates of CRC are both ranked top 5 among malignant tumors worldwide and continue to rise. Patients who receive treatment in the early stage (stage I) have a 5-year survival rate of approximately 90%. However, for high-risk stage II and III colorectal cancer patients, the 5-year survival rate is only 40%-70%, and almost half of the patients experience postoperative recurrence and metastasis.
Circulating tumor DNA (ctDNA) is a small fraction of total cell-free DNA (cfDNA) in peripheral blood circulation, carrying tumor-specific genetic and epigenetic information. It can usually be detected in the serum or plasma of tumor patients in peripheral blood. Studies have shown that methylation detection of plasma ctDNA can be used for predicting the efficacy and prognosis of tumor postoperatively, as well as for dynamic monitoring.
Current methods for monitoring CRC recurrence include testing for carcinoembryonic antigen (CEA) in blood and periodic computed tomography (CT) scans. However, due to the low sensitivity of CEA and the radiation and cost limitations of CT examination, the disease status of postoperative CRC patients cannot be well-monitored.
ctDNA is a promising biomarker for monitoring the recurrence and metastasis of CRC. Research results have shown that ctDNA can be detected in nearly all subjects before surgery, and the changes in ctDNA levels are related to the extent of surgical resection. The detection of ctDNA after surgery generally indicates recurrence within one year. ctDNA may be a more reliable and sensitive indicator than the current standard biomarker CEA, providing a window for early intervention.
This multicenter, prospective, and randomized controlled cohort study uses a single-tube methylation-specific quantitative PCR (mqMSP) detection, which detects 10 different methylation markers and can quantitatively analyze plasma samples containing tumor DNA as low as 0.05%. This study will use the ctDNA methylation detection technology to conduct quantitative detection of ctDNA methylation in the plasma of enrolled patients, hoping to predict the recurrence and metastasis risk of patients at an earlier stage through ctDNA changes, and to explore the value of ctDNA detection in guiding postoperative follow-up for non-metastatic CRC.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 526
- Age ≥ 18 and ≤80 years old, regardless of gender;
- Personal status (PS) score as over 80 or Eastern Cooperative Oncology Group (ECOG) score as 0 ~ 2;
- Preoperative imaging examinations reveal no definite distant metastatic lesions, and postoperative pTNM staging confirms patients with stage I to III colorectal cancer;
- Radical operation performed ;
- With expected survival of more than 12 months;
- The subjects (or their legal representative / Guardian) must sign the informed consent form, indicating that they understand the purpose of the study, understand the necessary procedures of the study, and are willing to participate in the study.
- Blood transfusion performed during operation or within 2 weeks before operation;
- Incomplete baseline samples, including preoperative plasma samples;
- Two consecutive test points missing or three plasma samples missing in total before a positive ctDNA time point;
- Pregnant or lactating women who have fertility and do not take adequate contraceptive measures;
- Have a history of other malignant tumors within 5 years, except cured cervical carcinoma in situ or non melanoma skin cancer;
- Primary brain tumor or central nerve metastasis is not under control, with obvious intracranial hypertension or neuropsychiatric symptoms;
- Patients with the following serious or uncontrollable diseases: severe heart disease, the condition is still unstable after treatment, including myocardial infarction, congestive heart failure, unstable angina pectoris, pericardial effusion with obvious symptoms or unstable arrhythmia within 6 months before enrollment; definite neuropathy or psychosis, including dementia or seizures; severe or uncontrolled infection; active disseminated intravascular coagulation and obvious bleeding tendency;
- Significant impairment of important organ function;
- Other conditions in which the investigator believes that the patient should not participate in this trial.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description ctDNA dynamic monitoring + routine postoperative follow-up ctDNA methylation dynamic monitoring Dynamic monitoring of ctDNA + routine postoperative follow-up: ctDNA detection is performed within one month before surgery, within one month after surgery, and every three months after surgery, for a period of 2 years. At the same time, routine postoperative follow-up is given. Follow-up intervention\*: After completion of adjuvant chemotherapy in the patient, if ctDNA detection suggests positive, immediate chest, abdomen, and pelvis CT and other imaging examinations are performed to determine whether there is recurrence or metastasis. If it is not confirmed, repeat imaging examinations are carried out every two months in the follow-up process, and ctDNA detection is continued every three months according to the schedule. If two consecutive ctDNA retests are negative, the above imaging follow-up will resume at the frequency of routine follow-up.
- Primary Outcome Measures
Name Time Method Accuracy of postoperative ctDNA methylation in monitoring recurrence and metastasis Up to 60 months True positive+True negative/sample size
Sensitivity of postoperative ctDNA methylation in monitoring recurrence and metastasis Up to 60 months Number of patients with ctDNA positive and imaging confirmed recurrence or metastasis / number of all imaging confirmed recurrence or metastasis
Specificity of postoperative ctDNA methylation in monitoring recurrence and metastasis Up to 60 months Number of patients with ctDNA negative and no recurrence and metastasis confirmed by imaging / number of patients with no recurrence and metastasis confirmed by imaging
Secondary resection rate Up to 60 months The rate of R0 resection for recurrence or metastasis after surgery of the primary
- Secondary Outcome Measures
Name Time Method Overall survival (OS) Up to 60 months Overall survival of included patients
ctDNA clearance rate Up to 60 months The rate of ctDNA positive before chemotherapy that turns negative after adjuvant chemotherapy
Disease free survival (DFS) Up to 60 months Disease free survival time under ctDNA monitoring; Disease free survival time under imaging monitoring; The difference between ctDNA-DFS and CT-DFS
Trial Locations
- Locations (1)
Fudan University Shanghai Cancer Center
🇨🇳Shanghai, Shanghai, China