Combined Immunotherapy and Targeted Therapy for Hepatocellular Carcinoma

Inclusion Criteria:

• Pathological diagnosis of primary hepatocellular carcinoma, BCLC stage A, liverfunction Chid-Pugh grade A, or liver function Child-Pugh classification changed fromgrade B to grade A after short-term liver treatment, PS score 0- 1 point. Receivedsurgical treatment of primary hepatocellular carcinoma (RO resection).

• Complete resection of postoperative macroscopic and imaging, no residual cancer;

• No large blood vessels (2-pole branches) and bile duct invasion, no macroscopic tumorthrombus;

• Negative margin: the margin of the liver is >1 cm from the tumor boundary; if themargin is <1 cm, but the histological examination of the resected liver section showedno residual tumor cells, that is, the margin was negative;

• AFP negative: <20 ug/L;

• No lymph node invasion, no distant metastasis;

• Laboratory inspection inclusion criteria:

• Neutrophils ≥ 1.5 × 109 / L;

• Platelets ≥ 50 × 109 / L;

• Hemoglobin ≥ 90 g / L;

• Serum creatinine ≤ 1.5 × upper limit of normal (ULN) and creatinine clearance ≥ 50 mL/min;

• AST, ALT ≤ 2.5 × ULN;

• Serum bilirubin ≤ 1.25 × ULN;

• Patients who did not receive anticoagulant therapy: INR or aPTT ≤ 1.5 × ULN. Ifthe patient received prophylactic anticoagulant therapy, the INR ≤ 2 × ULN within 14 days before the study treatment and the aPTT was within the normal range, thepatients were acceptable for enrollment.

• With one of the following high risk factors:

• Single lesion >5cm;

• Single lesion, 3-5cm, with MVI M1/M2;

• Single lesion, <3cm, MVI M2;

• Multiple lesions (2-3)

• General inclusion criteria:

• Age 18-75;

• No anti-tumor treatment history before surgery;

• Agree to provide tissue and pathological specimens;

• ECOG 0 points;

• For women of gestational age, no pregnancy plan and continued full contraception.

Exclusion Criteria:

• Pathological diagnosis of primary hepatocellular carcinoma, BCLC stage B, C, D, liverfunction Child-Pugh grade C, PS score of 2 points and above. Biliary cells or mixedcell carcinoma confirmed by postoperative pathology. No surgery was performed.

• Preoperative treatment of TACE or radiotherapy and chemotherapy, and targetedanti-tumor therapy.

• One month after the operation, the rest of the anti-tumor treatment was performed, orcombined with two or more anti-tumor pain treatment.

• There were lymph nodes and distant metastases before surgery.

• Have a history of active autoimmune disease or autoimmune disease;

• Inoculated with any anti-infective vaccine (such as influenza vaccine, varicellavaccine, etc.) within 4 weeks before randomization;

• Use immunosuppressive agents, or systemic, or absorbable local hormones to achieveimmunosuppressive purposes (dose > 10 mg/day of prednisone or other equivalenthormones) and continue to be used within 2 weeks prior to randomization;

• Any significant clinical and laboratory abnormalities;

• Researchers believed that the patient effected safety evaluation, such as:uncontrollable active infections, uncontrolled diabetes, high blood pressure could notbe reduced to the following range by monotherapy (systolic blood pressure < 140 mmHg,diastolic blood pressure < 90 mmHg), peripheral neuropathy grade II or above,congestive heart failure, myocardial infarction within 6 months, chronic kidneydisease;

• Main or main branch tumor thrombus (preoperative imaging or intraoperative findings)or extrahepatic disseminated or recurrent liver cancer.