Overview
This study is an open-label, randomized controlled, multicenter, phase III clinical trial
Description
This study is an open-label, randomized controlled, multicenter, phase III clinical trial where participants are randomized in a 1:1 ratio to either the experimental or control group. The experimental group will initiate radiotherapy within 4 months postoperatively with prescribed doses of 44-50Gy in 22-25 fractions to the tumor bed and 56-60Gy in 22-25 fractions to narrow-margin areas adjacent to major blood vessels, along with concurrent sintilimab 200mg q3w for 2 cycles followed by maintenance sintilimab 200mg q3w for 15 cycles (approximately 1 year total treatment duration) until disease progression or unacceptable toxicity. The control group will receive the first TACE procedure within 4 months postoperatively, with the decision on administering a second TACE to be determined by the investigator based on the patient's condition and first TACE response assessment. The primary endpoint is 2-year recurrence-free survival (RFS) rate, while secondary endpoints include 2-year overall survival (OS) rate and incidence of adverse events.
Eligibility
Inclusion Criteria:
- R0 resection of hepatocellular carcinoma (HCC) with a surgical margin <1 cm (determined by postoperative pathology, surgical records, and imaging).
- Within 4 months after curative resection.
- High-Risk Recurrence Factors (at least one required in addition to narrow margin): (1) Microvascular invasion (MVI) positive, tumor thrombus, or satellite nodules (2) Preoperative AFP >400 ng/mL (3) Tumor >5 cm with incomplete capsule
- ≥18 and ≤80 years old.
- ECOG score 0-1.
- Child-Pugh Class: A5, A6, or B7.
- Postoperative Contrast-enhanced MRI of the liver must be performed to exclude intrahepatic residual lesions.
- HBV DNA and HCV RNA status do not affect eligibility, but if HBV DNA positive and/or HCV RNA positive: ALT must be <1.5× upper limit of normal (ULN). Antiviral therapy must be initiated.
- Liver Function Tests (LFTs): ALT ≤2.5× ULN (if HBV/HCV positive, ALT ≤1.5× ULN). If ALT ≤1.5× ULN, AST ≤6× ULN (excluding AST elevation due to myocardial infarction). If ALT 1.5-2.5× ULN, AST ≤2.5× ULN.
- No significant ECG abnormalities and no severe cardiac dysfunction.
- Serum creatinine (CRE) and BUN ≤2.5× ULN.
- Hb≥80g/L，ANC≥1.0×109 /L，PLT≥40×109 /L.
- Written informed consent obtained.
Exclusion Criteria:
- Vp3 or Vp4 portal vein tumor thrombus (PVTT) or Vv2/Vv3 inferior vena cava (IVC) tumor thrombus on preoperative imaging.
- Previous anti-HCC therapies, including but not limited to: targeted therapy (e.g., tyrosine kinase inhibitors), immune checkpoint inhibitors (e.g., PD-1/PD-L1 inhibitors) or systemic chemotherapy
- Distant metastasis before randomization.
- Moderate to severe ascites unresponsive to medical management.
- History of other malignancies, except: carcinoma in situ，early-stage papillary thyroid cancer or basal cell carcinoma of the skin
- Previous radiotherapy involving the abdomen.
- Significant cardiac, renal, or other major organ dysfunction.
- Active Autoimmune Disease or Psychiatric Disorders.
- HIV Infection.
- Pregnant or breastfeeding women.
- Currently enrolled in another interventional clinical trial.