Patient case: 68-year-old male with colon cancer; genetic feature: MLH1 methylation suppression (microsatellite instability)

Clinical trial: Dynamic Monitoring of ctDNA Methylation to Predict Relapse in Stage II-III Colorectal Cancer After Radical Resection

Summary: This is a prospective, multicenter, observational, single-blinded controlled study. Dynamic monitoring of patients with stage II-III colorectal cancer was performed using the previously established colorectal tumor-specific plasma ctDNA methylation markers (diagnostic model established by next-generation sequencing of 2181 gene loci methylation). The methylation marker had a sensitivity of 93% in colorectal cancer patients with a specificity of 99% in healthy individuals. Dynamic monitoring of high-throughput next-generation sequencing of plasma ctDNA methylation before and after treatment and at regular follow-up in patients with colorectal cancer after radical resection of stage II-III colorectal cancer, to explore the predictive effect of postoperative plasma ctDNA methylation on postoperative recurrence and whether dynamic monitoring of postoperative ctDNA methylation could be earlier than imaging examination to indicate tumor recurrence.

Detailed description: At present, the main treatment of stage II-III CRC (CRC) is surgical resection. CRC patients after radical surgery have good overall survival. However, there are still a large number of patients with postoperative recurrence. The postoperative recurrence rate of stage II CRC patients is 20-30%, and that of stage III CRC patients is 50-60%. Currently, there is no effective measures to predict whether patients suffer postoperative relapse. Patients can only periodically visit doctors in the hope of timely treatment in case of recurrence. Current clinical monitoring methods mainly include imaging detection and tumor markers detection. However, long-term monitoring may affect patients' quality of life and increase patients' economic burden. Therefore, biomarkers that can predict the prognosis of patients and screen out those who need intensive follow up are urgently warranted. At present, imaging is the mainly used approach to monitor tumor recurrence. Quantitative determination of ctDNA methylation in plasma may find tumor recurrence trend before imaging detection, indicating that quantitative determination of ctDNA methylation in plasma is a more sensitive monitoring approach than traditional imaging detection. Can next-generation sequencing of the plasma ctDNA methylation be a new recurrence monitoring technique and prognostic prediction method of stage II-III CRC in clinical practice? In this study, we aimed to monitor the dynamic level of plasma ctDNA methylation after surgery in patients with stage II-III CRC, and to explore the advantages of plasma ctDNA methylation detection over traditional CRC in recurrence monitoring and prognosis prediction. This is a prospective, multicenter, observational, single-blinded controlled study. Dynamic monitoring of patients with stage II-III CRC was performed using the previously established colorectal tumor-specific plasma ctDNA methylation markers (diagnostic model established by next-generation sequencing of 2181 gene loci methylation). The methylation marker had a sensitivity of 93% in CRC patients with a specificity of 99% in healthy individuals. Dynamic monitoring of high-throughput next-generation sequencing of plasma ctDNA methylation before and after treatment and at regular follow-up in patients with CRC after radical resection of stage II-III CRC, to explore the predictive effect of postoperative plasma ctDNA methylation on postoperative recurrence and whether dynamic monitoring of postoperative ctDNA methylation could be earlier than imaging examination to indicate tumor recurrence.

Eligibility: Inclusion Criteria:
  -  Male or female ≥ 18 years of age on the day of signing informed consent.
  -  Patients must have histologically confirmed stage II/III colorectal cancer.
  -  Patients need to receive surgical resection.
  -  Patients must have a performance status of ≤1 on the ECOG Performance Scale.
  -  Life expectancy of more than 5 years.
  -  Written informed consent must be obtained from patient or patient's legal representative and ability for patient to comply with the requirements of the study.
  Exclusion Criteria:
  -  Patients received adjuvant treatment prior to the surgical resection.
  -  Patients received blood transfusion two weeks before or during the surgical resection.
  -  Patients with unresected advanced colorectal adenoma.
  -  Patients who are positive for Human Immunodeficiency Virus (HIV), Hepatitis B or Hepatitis C.
  -  Patients who are pregnant.
  -  Patients who are alcoholic or drug abusers.
  -  Patients with a history or current evidence of any condition or abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the Investigator.

Relevance to patient case: not relevant