Combination of SBRT and Immunotherapy in Small Hepatocellular Carcinoma (HSBRT2402)

A total of 140 patients with recurrent or residual small HCC will be stratified according to tumor diameter (≤3 vs. >3 cm) and tumor type (recurrent vs. residual) and randomly assigned (1:1) to receive stereotactic body radiotherapy (SBRT) with or without adjuvant sintilimab for 6 cycles (200 mg, once every 3 weeks, with the first dose within 1 week after the completion of SBRT).

Inclusion criteria

• Histologically confirmed hepatocellular carcinoma or diagnosed by American Association for the Study of Liver Disease criteria;
• Presence of recurrent or residual HCC lesions without vascular invasion or extrahepatic metastasis confirmed by CT or MRI, the sum of the maximum diameter of lesions ≤5 cm, total number of lesions were ≤2, and at least one of which is measurable according to the RECIST 1.1 Criteria;
• Previous molecular targeted therapy or intravenous chemotherapy is allowed, but the interval of drug withdrawal was at least 6 months prior to protocol therapy;
• Age at diagnosis 18 to 75 years;
• Eastern Cooperative Oncology Group performance status ≤ 2
• Child-Pugh class A liver function;
• Normal liver volume greater than 700 ml;
• Estimated life expectancy ≥24 weeks;
• 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;
• Ability to understand the study and sign informed consent.

Exclusion criteria

• Patients who have previously been treated with immune checkpoint inhibitors;
• Patients with extrahepatic metastasis disease;
• A history of abdominal radiotherapy;
• Known or suspected allergy or hypersensitivity to monoclonal antibodies;
• Patients who have a preexisting or coexisting bleeding disorder;
• Female patients who are pregnant or lactating;
• Inability to provide informed consent due to psychological, familial, social and other factors;
• A history of malignancies other than hepatocellular carcinoma before enrollment, excluding non-melanoma skin cancer, in situ cervical cancer, or cured early prostate cancer;
• A history of diabetes for more than 10 years and poorly controlled blood glucose levels;
• Patients who cannot tolerate radiotherapy due to severe cardiac, lung, liver or kidney dysfunction, or hematopoietic disease or cachexia;
• 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;
• A history of interstitial lung disease or non-infectious pneumonia;
• 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;
• 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);
• Any unstable situation that may endanger the safety and compliance of patients.