Hepatic Arterial Infusion Chemotherapy Plus Sintilimab and Bevacizumab Versus Transarterial Chemoembolization Plus Sintilimab and Bevacizumab for Intermediate-Stage Hepatocellular Carcinoma Beyond the Up-To-Seven Criteria：A Prospective, Randomized, Controlled Trial
Objective: To compare Progression-Free Survival (PFS) between the two arms as evaluated by mRECIST. Enrollment: A total of 300 patients will be randomized at a 1:1 ratio to the treatment groups. The study aims to provide high-level clinical evidence for optimizing treatment strategies for this specific subgroup of HCC patients.
• Diagnosis: Histologically or cytologically confirmed hepatocellular carcinoma (HCC), or patients with cirrhosis meeting the American Association for the Study of Liver Diseases (AASLD) clinical diagnostic criteria for HCC.
• Age: ≥ 18 years old.
• Performance Status: ECOG performance status score of 0.
• Prior Treatment: No prior systemic anti-tumor therapy or transarterial interventional therapy for HCC.
• Tumor Stage and Burden: Barcelona Clinic Liver Cancer (BCLC) Stage B, unsuitable for radical surgery and/or local therapy (such as ablation).
• Up-To-Seven Criteria: Tumor burden exceeding the Up-To-Seven criteria, defined as the sum of the size of the largest intrahepatic tumor (in cm) and the number of tumors being greater than 7.
• Tumor Distribution: Bilobar multifocal tumors.
• Measurable Disease: At least one measurable lesion with arterial phase enhancement on CT/MRI.
• Vascular Status: Patent portal vein with no evidence of portal vein tumor thrombus.
• Extrahepatic Status: No extrahepatic metastasis.
• Variceal Risk: No risk of variceal bleeding; esophagogastroduodenoscopy (EGD) within 6 months shows no gastroesophageal varices or active ulcers.
• Liver Function: Child-Pugh Grade A.
• Hematology: Platelets \> 75 × 10⁹/L; White Blood Cells \> 3.0 × 10⁹/L; Neutrophils \> 1.5 × 10⁹/L.
• Biochemistry: Serum bilirubin ≤ 1.5 × upper limit of normal (ULN); Transaminases ≤ 3 × ULN; Serum creatinine \< 1.5 × ULN.
• Physical Findings: No ascites
• Albumin ≥ 30 g/L.
• Coagulation: Normal coagulation function.
• Expectancy: Expected survival \> 3 months.
• Consent: Signed written informed consent and willingness/ability to comply with follow-up until death, study completion, or termination.