Adjuvant Radiotherapy of Sintilimab Versus TACE for HCC

Adjuvant Radiotherapy Combined With Sintilimab Versus Transarterial Chemoembolization (TACE) for Hepatocellular Carcinoma With Narrow Margins and High-Risk Features Following Resection: A Multi-center Phase III Randomized Controlled Trial

This study is an open-label, randomized controlled, multicenter, phase III clinical trial

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.

Inclusion Criteria:

1. R0 resection of hepatocellular carcinoma (HCC) with a surgical margin <1 cm (determined by postoperative pathology, surgical records, and imaging).
2. Within 4 months after curative resection.
3. 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
4. ≥18 and ≤80 years old.
5. ECOG score 0-1.
6. Child-Pugh Class: A5, A6, or B7.
7. Postoperative Contrast-enhanced MRI of the liver must be performed to exclude intrahepatic residual lesions.
8. 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.
9. 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.
10. No significant ECG abnormalities and no severe cardiac dysfunction.
11. Serum creatinine (CRE) and BUN ≤2.5× ULN.
12. Hb≥80g/L，ANC≥1.0×109 /L，PLT≥40×109 /L.
13. Written informed consent obtained.

Exclusion Criteria:

1. Vp3 or Vp4 portal vein tumor thrombus (PVTT) or Vv2/Vv3 inferior vena cava (IVC) tumor thrombus on preoperative imaging.
2. 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
3. Distant metastasis before randomization.
4. Moderate to severe ascites unresponsive to medical management.
5. History of other malignancies, except: carcinoma in situ，early-stage papillary thyroid cancer or basal cell carcinoma of the skin
6. Previous radiotherapy involving the abdomen.
7. Significant cardiac, renal, or other major organ dysfunction.
8. Active Autoimmune Disease or Psychiatric Disorders.
9. HIV Infection.
10. Pregnant or breastfeeding women.
11. Currently enrolled in another interventional clinical trial.