Combined Immunotherapy and Targeted Therapy for Hepatocellular Carcinoma

Inclusion Criteria:

• Pathological diagnosis of primary hepatocellular carcinoma, BCLC stage A, liver function Chid-Pugh grade A, or liver function Child-Pugh classification changed from grade B to grade A after short-term liver treatment, PS score 0- 1 point. Received surgical 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 tumor thrombus;
• Negative margin: the margin of the liver is >1 cm from the tumor boundary; if the margin is <1 cm, but the histological examination of the resected liver section showed no 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. If the patient received prophylactic anticoagulant therapy, the INR ≤ 2 × ULN within 14 days before the study treatment and the aPTT was within the normal range, the patients 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, liver function Child-Pugh grade C, PS score of 2 points and above. Biliary cells or mixed cell carcinoma confirmed by postoperative pathology. No surgery was performed.
• Preoperative treatment of TACE or radiotherapy and chemotherapy, and targeted anti-tumor therapy.
• One month after the operation, the rest of the anti-tumor treatment was performed, or combined 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, varicella vaccine, etc.) within 4 weeks before randomization;
• Use immunosuppressive agents, or systemic, or absorbable local hormones to achieve immunosuppressive purposes (dose > 10 mg/day of prednisone or other equivalent hormones) 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 not be 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 kidney disease;
• Main or main branch tumor thrombus (preoperative imaging or intraoperative findings) or extrahepatic disseminated or recurrent liver cancer.