Combination of Sintilimab and Stereotactic Body Radiotherapy in Hepatocellular Carcinoma (ISBRT01)

Inclusion Criteria:

1. Histologically confirmed hepatocellular carcinoma or diagnosed by American Association for the Study of Liver Disease criteria;
2. No previous treatment for hepatocellular carcinoma, and received arterially directed therapy (transarterial chemoembolization or hepatic arterial infusion chemotherapy) as initial treatment and achieved technical success;
3. Absence of extrahepatic metastasis disease;
4. Portal vein invasion (at least the first- or second-branch portal vein) confirmed by 2 imaging techniques;
5. Less than 3 active intrahepatic lesions with a total diameter of less than 15 cm were required, at least one of which is measurable according to the mRECIST Criteria;
6. Age at diagnosis 18 to 75 years;
7. Eastern Cooperative Oncology Group performance status ≤ 2
8. Child-Pugh class A liver function;
9. Normal liver volume greater than 700 ml;
10. Estimated life expectancy ≥12 weeks;
11. The function of important organs meets the following requirements: a. white blood cell count (WBC) ≥ 3.0×109/L, absolute neutrophil count (ANC) ≥ 1.5×109/L; b. platelets ≥ 50×109/L; c. hemoglobin ≥ 9g/dL; d. serum albumin ≥ 2.8g/dL; e. total bilirubin ≤ 1.5×ULN, ALT, AST and/or AKP ≤ 2.5×ULN; f. serum creatinine ≤ 1.5×ULN or creatinine clearance rate \>60 mL/min;
12. Ability to understand the study and sign informed consent.

Exclusion Criteria:

1. Patients who have been treated previously with systemic anti-tumor therapy (including chemotherapy, molecule-targeted therapy, immunotherapy, etc.);
2. Patients with extrahepatic metastasis disease at diagnosis;
3. The total diameter of the active intrahepatic lesions was more than 15 cm;
4. A history of abdominal radiotherapy;
5. Known or suspected allergy or hypersensitivity to monoclonal antibodies;
6. Patients who have a preexisting or coexisting bleeding disorder;
7. Female patients who are pregnant or lactating;
8. Inability to provide informed consent due to psychological, familial, social and other factors;
9. A history of malignancies other than hepatocellular carcinoma before enrollment, excluding non-melanoma skin cancer, in situ cervical cancer, or cured early prostate cancer;
10. A history of diabetes for more than 10 years and poorly controlled blood glucose levels;
11. Patients who cannot tolerate radiotherapy due to severe cardiac, lung, liver or kidney dysfunction, or hematopoietic disease or cachexia;
12. Active autoimmune diseases, a history of autoimmune diseases (including but not limited to these diseases or syndromes, such as colitis, hepatitis, hyperthyroidism), a history of immunodeficiency (including a positive HIV test result), or other acquired or congenital immunodeficiency diseases, a history of organ transplantation or allogeneic bone marrow transplantation;
13. A history of interstitial lung disease or non-infectious pneumonia;
14. A history of active pulmonary tuberculosis infection within 1 year or a history of active pulmonary tuberculosis infection more than 1 year ago but without formal anti-tuberculosis treatment;
15. Presence of active hepatitis B (HBV DNA ≥ 2000 IU/mL or 104 copies/mL), hepatitis C (positive for hepatitis C antibody, and HCV-RNA levels higher than the lower limit of the assay);
16. Any unstable situation that may endanger the safety and compliance of patients.