SBRT + PD-1 Monoclonal Antibody in Unresectable Colorectal Liver Metastases

Inclusion Criteria:

1. Written informed consent, voluntarily signed and dated by the subject, must beobtained in accordance with regulatory and institutional guidelines before anyprocedures related to the study protocol that are not part of routine care areperformed.

2. Patients with pMMR/MSS colorectal adenocarcinoma;

3. Age 18-75 years;

4. Patients with histologically or cytologically confirmed colorectal cancer livermetastasis, with or without extrahepatic oligometastatic lesions, who are deemed bythe hepatobiliary surgeon within the multidisciplinary team (MDT) to be ineligiblefor upfront R0 resection of liver metastases (unresectability is defined as one ormore of the following conditions: ① Involvement of both left and right branches ofthe portal vein at the first hepatic hilum; ② Involvement of ≥2 hepatic veins at thesecond hepatic hilum; ③ No indication for upfront R0 resection/ablation after MDTdiscussion);

5. Liver metastases are measurable by imaging (based on RECIST 1.1 criteria), with amaximum diameter of ≤6 cm;

6. Patients who have not previously received radiotherapy for liver metastases, orwhose liver tissue near the planned irradiation site has not been previouslyirradiated, and who have at least 700 cc of liver volume outside the treatment area;

7. Previous hepatectomy, systemic chemotherapy, or local ablation therapy, or hepaticarterial infusion pump chemotherapy is allowed, with a washout period of 2 weeks;

8. Child-Pugh score Class A ;

9. ECOG performance status 0-1;

10. Peripheral blood counts and liver and renal function within allowable ranges (testedwithin 15 days before the start of treatment);

11. No history of other malignancies, not pregnant or breastfeeding, and effectivecontraception should be used during the study period and for 6 months after the lastdose;

12. Life expectancy of ≥6 months.

Exclusion Criteria:

1. Active hepatitis, cirrhosis, or Child-Pugh score Class B or C;

2. Extrahepatic metastases: bone or brain metastases, or ≥3 unresectable lungmetastases (according to the 8th edition of the UICC);

3. Unmeasurable liver metastases;

4. History of severe drug allergies (including allergies to platinum agents, 5-FU, LV,and 5-HT3 receptor antagonists);

5. Patients who have participated in or are currently participating in other clinicaltrials within the past 4 weeks;

6. History of prior treatment with anti-PD-1, PD-L1, PD-L2, CTLA-4, or any otherspecific T-cell costimulatory or checkpoint pathway-targeted therapies;

7. Severe electrolyte abnormalities;

8. Presence of gastrointestinal diseases, such as active gastric or duodenal ulcers,ulcerative colitis, or unresected tumors with active bleeding; or other conditionsthat may lead to gastrointestinal bleeding or perforation (Note: Gastrointestinalfistulas that have not healed after surgical treatment, such as rectovesical,rectourethral, or rectovaginal fistulas, are exclusionary unless a stoma has beencreated and there are no active symptoms);

9. History of arterial thrombosis or deep vein thrombosis within 6 months; history ofbleeding or evidence of bleeding tendency within 2 months;

10. Pregnant or breastfeeding women, or women of childbearing potential with a positivepregnancy test before the first dose; or female participants unwilling to strictlypractice contraception during the study, as well as their partners;

11. Patients with active autoimmune deficiency diseases requiring systemic treatmentwithin the past 2 years (i.e., use of immunomodulators, corticosteroids, orimmunosuppressive drugs);

12. Presence of other active malignancies (except for malignancies that have beentreated with curative intent and have been disease-free for over 3 years, or in situcancers that can be cured with adequate treatment);

13. Presence of severe ECG abnormalities or active coronary artery disease within 12months before study entry, severe/unstable angina, newly diagnosed angina ormyocardial infarction, or New York Heart Association (NYHA) Class II or highercongestive heart failure;

14. Patients with active infections (fever above 38°C due to infection);

15. Patients with poorly controlled hypercalcemia, hypertension, or diabetes;

16. Patients with severe pulmonary diseases (interstitial pneumonia, pulmonary fibrosis,severe emphysema, etc.);

17. Patients with psychiatric disorders affecting clinical management or a history ofcentral nervous system diseases;

18. Patients with severe complications (intestinal obstruction, renal insufficiency,hepatic insufficiency, cerebrovascular disorders, etc.);

19. Presence of any CTCAE Grade 2 or higher toxicity from prior treatments that has notresolved (except for anemia, alopecia, and skin pigmentation);

20. Any unstable medical condition that may affect patient safety or compliance with thestudy;

21. Patients deemed by the investigator to be unsuitable for participation in thisclinical trial.