Circulating Tumor DNA Methylation-Guided Adjuvant Therapy Decision-Making in Patients With Resectable Colorectal Cancer Liver Metastases After Resection

Ki vehet részt

• Age 18 to 75 years, regardless of sex
• Histopathologically confirmed colorectal adenocarcinoma with liver metastases confirmed by contrast-enhanced CT or MRI
• Liver metastases assessed as resectable by a multidisciplinary team, with R0 resection completed. Simultaneous or staged resection of the primary tumor and liver metastases is permitted. R0 resection is defined as negative surgical margins with no macroscopic or microscopic residual disease
• No residual disease on contrast-enhanced CT or MRI performed within one month after surgery, confirming no evidence of disease (NED)
• No previous systemic anticancer treatment for metastatic disease, including chemotherapy, targeted therapy, or immunotherapy. If prior neoadjuvant or adjuvant chemotherapy was administered, the interval between the last dose and the diagnosis of liver metastases must be at least six months
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Postoperative peripheral blood samples (two 10-mL tubes) can be obtained for ctDNA methylation testing
• Able to understand and voluntarily sign written informed consent
• Willing and able to comply with the follow-up schedule specified in the study protocol

Ki nem vehet részt

• Previous local treatment of the primary tumor or metastatic lesions, such as radiofrequency ablation or radiotherapy, without complete tumor eradication
• Microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) status and considered suitable for immunotherapy by the investigator
• Residual disease confirmed by imaging one month after surgery, indicating that NED has not been achieved
• Uncontrolled severe hypertension (persistent systolic blood pressure >160 mmHg or diastolic blood pressure >100 mmHg), severe infection, active hepatitis B (HBV DNA >1000 copies/mL), hepatitis C (positive HCV RNA), or human immunodeficiency virus infection
• History of serious cardiovascular or cerebrovascular disease, including New York Heart Association (NYHA) functional class III or higher, myocardial infarction or unstable angina within the past six months, or uncontrolled arrhythmia
• Known allergy or contraindication to chemotherapy agents potentially used in the study (oxaliplatin, irinotecan, 5-fluorouracil, or capecitabine) or targeted agents (cetuximab beta or bevacizumab)
• Other malignancies, except non-melanoma skin cancer or cervical carcinoma in situ that has been treated curatively with no evidence of recurrence for more than five years
• History of alcohol abuse or drug abuse
• Cognitive impairment or severe psychiatric illness that prevents understanding of or compliance with study requirements
• Severe hepatic or renal dysfunction (ALT/AST >3 times the upper limit of normal [ULN], total bilirubin >1.5 times ULN, or creatinine >1.5 times ULN), or impaired bone marrow function (white blood cell count <3.0 × 10\^9/L, neutrophil count <1.5 × 10\^9/L, platelet count <75 × 10\^9/L, or hemoglobin <90 g/L)
• Any other clinical or laboratory condition that, in the investigator's opinion, makes the participant unsuitable for this study
• Non-adenocarcinoma histology, such as neuroendocrine tumor, squamous cell carcinoma, or adenosquamous carcinoma
• Extrahepatic metastases, including metastases to the lungs, bones, brain, peritoneum, or distant lymph nodes
• Pregnancy or breastfeeding, or refusal by participants of reproductive potential to use effective contraception during the study