Neoplasms

Digestive System Diseases

All Conditions

Immune System Diseases

Colorectal Neoplasms

Hypersensitivity

Adenoma

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Patients with colorectal cancer and advanced adenoma.

Healthy participants and patients with benign colorectal disease.

Detection for colorectal tumor-specific ctDNA methylation biomarkers

Genome-wide methylation profiling

Jun Yan, M.D., Ph.D.

This is a prospective diagnostic study. This study is to compare the performance between circulating tumor DNA (ctDNA) methylation and carcinoembryonic antigen (CEA) in detecting colorectal tumor. Firstly, based on the identification of differential ctDNA methylation biomarkers, the diagnostic model is established and the diagnostic performance was compared with that of CEA. Secondly, the stage stratification model was established preliminarily based on differential ctDNA methylation biomarkers and the performance was also compared with that of CEA.

Colorectal cancer (CRC) is the third most common cancer worldwide, the second deadliest cancer. It is reported that patients prefer non-invasive methods rather than invasive methods for the detection of CRC. Carcinoembryonic antigen (CEA) is commonly employed in clinical practice for early detection of CRC, but it is limited for its low sensitivity, which is around 30%-40%. DNA methylation is a commonly used biomarker for non-invasive tumor detection in plasma. We aim to develop and validate a ctDNA methylation-based blood test for CRC diagnosis based on genome-wide methylation detection. There are two steps in the study. Firstly, this prospective study aims to identify colorectal tumor differential circulating tumor DNA (ctDNA) methylation biomarkers, establish the diagnostic model. Secondly, we performed a preliminary study to stratify early-stage and advanced-stage disease based on the differential biomarkers.

Comparison of Diagnostic Sensitivity Between ctDNA Methylation and CEA in Colorectal Cancer

Comparison of Diagnostic Sensitivity Between Circulating Tumor DNA Methylation and Carcinoembryonic Antigen in Colorectal Cancer

The comparison of sensitivity between ctDNA methylation and CEA in detecting colorectal cancer

The performance of the novel model to stratify early-stage and advanced-stage disease, and comparing with that of CEA.

Nanfang Hospital, Southern Medical University

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.

Routine postoperative follow-up: Only routine postoperative follow-up is given as follows: Physical examination and CEA were performed every 3-6 months for the first 2 years, every 6 months within the third to fifth year, and then annually. Chest/abdominal/pelvis computed tomography was performed annually for up to 5 years, and colonoscopy was performed for proper patients the first year after treatment and repeated in the third year if no advanced adenoma was found and then every 5 years.

ctDNA methylation 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.

ctDNA methylation dynamic monitoring

Junjie Peng, MD, PhD

Shaobo Mo, MD, PhD

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.

Circulating Tumor DNA Methylation Guided Postoperative Follow-up Strategy for Non-metastatic Colorectal Cancer

Circulating Tumor DNA Methylation Guided Postoperative Follow-up Strategy for Non-metastatic Colorectal Cancer: a Multicenter, Prospective, Randomized Controlled Cohort Study (FIND Trial)

Number of patients with ctDNA positive and imaging confirmed recurrence or metastasis / number of all imaging confirmed recurrence or metastasis

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

The rate of R0 resection for recurrence or metastasis after surgery of the primary

Disease free survival time under ctDNA monitoring; Disease free survival time under imaging monitoring; The difference between ctDNA-DFS and CT-DFS

The rate of ctDNA positive before chemotherapy that turns negative after adjuvant chemotherapy

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Comparison of Diagnostic Sensitivity Between ctDNA Methylation and CEA in Colorectal Cancer	NCT05558436	Colorectal Tumo...	Genome-wide met...	18 Years - 80 Years	Nanfang Hospital, Southern Medical University
Comparison of Diagnostic Sensitivity Between ctDNA Methylation and CEA in Colorectal Cancer	NCT05558436	Colorectal Tumo...	Genome-wide met...	18 Years - 80 Years	Nanfang Hospital, Southern Medical University
Circulating Tumor DNA Methylation Guided Postoperative Follow-up Strategy for Non-metastatic Colorectal Cancer	NCT05904665	Non-metastatic ... Circulating Tum...	ctDNA methylati...	18 Years - 80 Years	Fudan University

Spots Global Cancer Trial Database for circulating tumor dna methylation