Inclusion Criteria:
* Aged 18 to 70 years, male or female.
* Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
* Histologically or cytologically confirmed colon adenocarcinoma, with pathologically or radiographically verified liver-only metastases.
* Microsatellite stable (MSS) / proficient mismatch repair (pMMR) confirmed by immunohistochemistry (IHC) or polymerase chain reaction (PCR).
* No prior local or systemic anti-tumor therapy for colon cancer liver metastases, including but not limited to targeted therapy, immunotherapy, systemic or hepatic arterial infusion chemotherapy, radiotherapy and surgery.
* Inclusion criteria for liver metastases: ① More than 5 liver metastatic lesions, with at least one lesion measuring less than 3 cm in diameter; ② Child-Pugh Class A; ③ Future Liver Remnant (FLR) / Standard Liver Volume (SLV) \> 30% for patients without liver cirrhosis, or \> 40% for patients with liver cirrhosis; ④ Exclude lesions involving complicated surgical sites, such as biliary tract reconstruction, vascular reconstruction, invasion of hepatic hilum, portal vein or inferior vena cava.
* At least one radiographically measurable lesion per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1).
* Expected survival of no less than 12 weeks.
* Laboratory test results meet the following criteria within 7 days prior to the first study drug administration (No blood products, hematopoietic growth factors, albumin or other corrective medications deemed necessary by the investigator shall be administered within 14 days before testing):
1. Biochemistry: Alkaline phosphatase (ALP), alanine transaminase (ALT) and aspartate transaminase (AST) ≤ 3 × upper limit of normal (ULN), or ≤ 5 × ULN in patients with liver metastases; Total bilirubin (TBIL) ≤ 1.5 × ULN, or ≤ 2 × ULN in patients with liver metastases; Serum creatinine ≤ 1.5 × ULN, or creatinine clearance \> 50 mL/min (calculated via Cockcroft-Gault formula).
2. Hematology: Hemoglobin (Hb) ≥ 9.0 g/dL; No red blood cell transfusion within 1 week (including the test day) before baseline Hb test; Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L; Platelet count ≥ 100 × 10⁹/L; No platelet transfusion within 1 week (including the test day) before baseline platelet test.
3. Coagulation function: International Normalized Ratio (INR) and activated partial thromboplastin time (APTT) ≤ 1.5 × ULN. For subjects receiving prophylactic anticoagulation without active bleeding (no bleeding within the past 14 days), INR ≤ 2 × ULN and APTT within normal range.
4. Urinalysis: Urinary protein ≤ 30 mg/dL (1+) by dipstick or routine urinalysis. If urine protein ≥ 2+, 24-hour urinary protein quantification shall be less than 1 g/24h.
* No contraindications to radiotherapy, chemotherapy or immunotherapy.
* For female subjects of childbearing potential: serum pregnancy test must be negative within 7 days prior to enrollment. They must agree to use effective contraception throughout the study and for 5 months after the last study drug administration. Male subjects with partners of childbearing potential must also use effective contraception during the study and for 5 months after the last dose. Lactating women are excluded.
* Subjects must be fully informed of the study prior to enrollment, voluntarily sign the written informed consent form, and be willing and able to comply with all scheduled visits, treatment plans, laboratory tests and other study procedures.
Exclusion Criteria:
* Confirmed non-adenocarcinoma pathological types via histopathology or cytopathology, including squamous cell carcinoma, undifferentiated carcinoma, neuroendocrine carcinoma, etc. For mixed pathological types, eligibility is determined by the predominant component; patients are eligible only if a pathologist confirms the adenocarcinoma component accounts for more than 70%. Patients with primary appendiceal tumors are excluded.
* Presence of distant metastases at sites other than the liver.
* Prior systemic treatment with anti-PD-1, anti-PD-L1, anti-CTLA-4 antibodies or other immunotherapeutic agents, or the CAPOX regimen. Prior radiotherapy for liver metastases, or prior radiation exposure to normal liver tissue adjacent to the planned irradiation field.
* History of other malignant tumors within 5 years prior to enrollment, except cured carcinoma in situ of the cervix, basal cell or squamous cell skin cancer, radically treated localized prostate cancer, and radically treated ductal carcinoma in situ.
* Active autoimmune diseases requiring systemic treatment (with immunomodulators, corticosteroids or immunosuppressants) within the past 2 years. Replacement therapies such as thyroxine, insulin, or physiological corticosteroids for adrenal or pituitary insufficiency are permitted and not regarded as systemic immunosuppressive treatment.
* Immunodeficiency, or receipt of long-term systemic corticosteroids (prednisone equivalent \> 10 mg per day) or other immunosuppressants within 7 days before enrollment or anticipated during study treatment.
* Uncontrolled pleural effusion, pericardial effusion, or moderate to severe ascites.
* Tumor-related complications such as bleeding, perforation or intra-abdominal infection within 3 months prior to enrollment.
* Clinically significant bleeding symptoms or high bleeding risk within 3 months prior to enrollment, including gastrointestinal hemorrhage, gastroesophageal varices, bleeding gastric ulcer, hematochezia, hematemesis or hemoptysis. Presence of gastrointestinal disorders including active peptic ulcer, ulcerative colitis, gastrointestinal perforation, unhealed gastrointestinal fistula, malabsorption syndrome or uncontrolled inflammatory bowel disease.
* Thrombotic or thromboembolic events including cerebrovascular accident, pulmonary embolism and deep vein thrombosis within 6 months prior to enrollment.
* Medical history of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonia or interstitial lung disease; or evidence of active pneumonia detected on contrast-enhanced chest CT.
* Any significant clinical or laboratory abnormalities judged by the investigator to compromise safety assessment, including uncontrolled active infection, poorly controlled diabetes, hypertension unresponsive to single-agent therapy, Grade ≥ 2 peripheral neuropathy, congestive heart failure, New York Heart Association (NYHA) Class ≥ II cardiac disease, myocardial infarction within 3 months prior to enrollment, unstable arrhythmia, unstable angina, chronic kidney disease and thyroid dysfunction.
* Major surgery performed within 28 days prior to enrollment without complete postoperative recovery.
* Active infection requiring systemic oral or intravenous treatment within 2 weeks prior to enrollment (excluding viral hepatitis and prophylactic medication).
* Patients with active tuberculosis, or those who received anti-tuberculosis therapy within 1 year prior to enrollment.
* For patients positive for hepatitis B surface antigen (HBsAg) and/or hepatitis B core antibody (HBcAb), HBV-DNA must be less than 500 IU/mL. Patients with active hepatitis B must have received antiviral therapy for at least 14 days before enrollment (e.g., entecavir or tenofovir per local guidelines) and agree to continue effective antiviral treatment throughout the study. For patients positive for HCV antibody, HCV-RNA testing is required; those with HCV-RNA \> 1000 copies/mL will be excluded.
* Positive human immunodeficiency virus (HIV) antibody.
* Administration of any live vaccine (e.g., influenza vaccine, varicella vaccine) within 28 days prior to enrollment.
* Prior allogeneic bone marrow transplantation or solid organ transplantation.
* Known allergy to any study drug or its excipients.
* History of uncorrected serum electrolyte disorders (e.g., hypokalemia, hypocalcemia, hypomagnesemia).
* Participation in other interventional clinical studies within 28 days prior to enrollment.
* Presence of clinically significant underlying diseases or other conditions judged by the investigator to interfere with study drug administration or protocol compliance.
