In this phase I single-arm clinical study, 20 patients with T4 unresectable locally advanced colon cancer are proposed to be enrolled, who will be treated with MR-Linac with short course radiotherapy (25Gy/5F), followed by 4 cycles of mFOLFOX6 or 3 cycles of XELOX chemotherapy, then radical surgical resection, and then postoperatively with 8 cycles of mFOLFOX6 or 5 cycles of XELOX. The study will assess patients' surgical R0 resection rate, pCR or cCR rate, PFS, OS, and related adverse effects of treatment, aiming to explore the feasibility, safety, and efficacy of MR-Linac in the treatment of unresectable locally advanced colon cancer.

Pre-specified run-in/feasibility phase. As outlined in the registered protocol, this record includes an initial feasibility (run-in) phase conducted under the same eligibility criteria and intervention as the definitive efficacy/safety phase. The run-in is designed solely to evaluate operational and workflow feasibility. The run-in is not powered for efficacy and will not test efficacy or survival hypotheses.

Pre-specified feasibility thresholds for proceeding include, for example: protocol adherence ≥85-90%, adaptive-plan success ≥80-90%, and accrual feasibility ≥80% of the target. The run-in sample size is capped (≈24 patients), and its endpoints/time frames are listed under Outcome Measures. Meeting these thresholds triggers continuation to the definitive phase without changing the intervention or eligibility.

Inclusion criteria:

1. Patients over 18 years old
2. Patients can remain in a stationary position on the treatment bed for 1-1.5 hours
3. ECOG score 0-1
4. Pathological diagnosis of colon adenocarcinoma, clinical stage cT4N0-2M0
5. Organ function is normal, and the following conditions are required: white blood cell count ≥3.5×10^9/L; platelet count ≥100×10^9/L; hemoglobin ≥90g/L. Total bilirubin level ≤1.5× upper limit of normal (ULN); AST and ALT levels ≤2.5 × ULN; endogenous creatinine clearance rate: 56-122ml/min; serum creatinine <1.0× ULN; serum albumin ≥30g/L.
6. Able to adhere to the study protocol during the research period
7. Signed written informed consent

Exclusion Criteria:

1. Patients with dMMR or MSI-H
2. Presence of other types of tumors in addition to colon adenocarcinoma
3. Claustrophobia or inability to undergo MRI or treatment due to the presence of metal implants or other reasons
4. Distant metastasis (M1)
5. Pregnant or lactating women
6. Previous anti-tumor treatment
7. Concurrent use of prohibited drugs for treatment
8. Known history of positive human immunodeficiency virus testing or known acquired immunodeficiency syndrome.
9. Clinically significant (i.e., active) cardiovascular disease: cerebrovascular accident/stroke (<6 months prior to enrollment), myocardial infarction (<6 months prior to enrollment), unstable angina pectoris, congestive heart failure (≥New York Heart Association class II) or severe arrhythmia requiring medication treatment
10. Individuals with uncontrolled epilepsy, central nervous system disorders or a history of mental illness, whose clinical severity may hinder signing informed consent or affect patient compliance with oral medication according to the investigator's judgement
11. Organ transplant surgery requiring immunosuppressive therapy
12. Severe, uncontrolled recurrent infections or other severe, uncontrolled comorbidities