Radiotherapy + Systemic Therapy as Conversion Therapy for pMMR/MSS T4M0 Colon Cancer（Neo-Color）

Inclusion criteria

• Age ≥18 years, no restriction on gender.
• ECOG performance status of 0-1.
• Histopathologically confirmed diagnosis of colon adenocarcinoma (including mucinous adenocarcinoma), identified as pMMR/MSS type; the primary tumor site must be specified (left colon defined as from the splenic flexure to the rectosigmoid junction, right colon defined as from the cecum to the proximal splenic flexure).
• Baseline imaging (enhanced CT/MRI) confirms clinical staging as cT4NanyM0 according to the AJCC 8th edition staging criteria.
• Laboratory criteria prior to enrollment must meet the following ranges:

(1) Hematology: Absolute neutrophil count ≥ 1.5 × 10^9/L, platelets ≥ 100 × 10^9/L, hemoglobin ≥ 90 g/L.

(2) Liver and renal function: ALT/AST ≤ 2.5 × ULN, total bilirubin ≤ 1.5 × ULN, creatinine ≤ 1.5 × ULN or creatinine clearance rate ≥ 60 mL/min (Cockcroft-Gault formula).

(3) Coagulation function: INR ≤ 1.5, APTT ≤ 1.5 × ULN (for those not on anticoagulation therapy).

6.Women of childbearing potential and men must agree to use effective contraception during the study and for 6 months after the last treatment.

7.Willingness to sign a written informed consent form and commit to completing the entire treatment and follow-up plan.

Exclusion criteria

• Histological type of neuroendocrine carcinoma, squamous cell carcinoma, or other non-adenocarcinoma components comprising more than 50%.
• Presence of distant metastasis (including peritoneal metastasis, non-regional lymph node metastasis, or organ metastasis).
• Previous radiotherapy, chemotherapy, targeted therapy, or immunotherapy for colon cancer.
• Active autoimmune diseases (e.g., systemic lupus erythematosus, rheumatoid arthritis requiring long-term immunosuppressive therapy).
• Active infections (e.g., HIV, positive HBV/HCV viral load requiring antiviral treatment for stabilization).
• Severe cardiovascular diseases (e.g., myocardial infarction within 6 months, unstable angina, uncontrolled hypertension >160/100 mmHg).
• History of other malignancies (except for cured non-melanoma skin cancer, cervical carcinoma in situ, etc., with a disease-free period of ≥5 years).
• Uncontrolled diabetes (HbA1c > 8%) or thyroid dysfunction (TSH outside the normal range requiring medication).
• Severe chronic bowel diseases (e.g., active Crohn's disease, ulcerative colitis).
• History of radiation enteritis or extensive abdominal adhesions affecting radiotherapy target delineation.
• Unrecovered bone marrow suppression (ANC < 1.5 × 10^9/L, PLT < 100 × 10^9/L, Hb < 90 g/L).
• Liver function with Child-Pugh score ≥ B or renal function with eGFR < 60 mL/min/1.73 m².
• Pregnant or breastfeeding women (blood/urine HCG test required during screening).
• Cognitive impairment or history of psychiatric disorders affecting treatment compliance.
• Concurrent participation in other interventional clinical trials.
• Patients deemed unsuitable for participation by the investigator.