BITS-TO-HCC Study: HAIC+Iparomlimab/Tuvonralimab + Bevacizumab + Surgery/SBRT for BCLC-C HCC With PVTT and/or Oligometastases

Inclusion Criteria:

1. Male or female patients aged between 18 and 70 years.
2. Unresectable HCC, BCLC Stage C according to the BCLC strategy-2026 update, with staging established via biopsy pathology and/or clinical diagnosis.
3. Child-Pugh class A without clinically significant hepatic decompensation; Eastern Cooperative Oncology Group (ECOG) performance status 0-1
4. Metastatic burden and local therapy eligibility

   * Extrahepatic oligometastatic disease defined as ≤3 involved organs with ≤5 total metastatic lesions
   * All intended intrahepatic and/or extrahepatic SBRT targets must satisfy protocol-specified target-coverage, liver reserve, and organ-at-risk (OAR) constraints within a composite 5-fraction plan
5. Prognosis \& measurable disease

   * Life expectancy ≥3 months
   * ≥1 measurable lesion (per RECIST 1.1):
   * Tumor: ≥10 mm (CT long axis)
   * Lymph node: ≥15 mm (CT short axis)
6. Prior therapy

   * Prior locoregional therapy permitted：radiofrequency ablation (RFA), TACE, or HAIC, provided that:
   * Documented radiographic progression or intolerance after the prior therapy
   * Washout ≥28 days
   * Treatment-related toxicities recovered to ≤Grade 1 (alopecia and peripheral neuropathy ≤Grade 2 allowed)
7. Laboratory and virologic requirements

   * Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) ≤5 × upper limit of normal (ULN); total bilirubin \<3 × ULN; serum albumin ≥28 g/L
   * Serum creatinine ≤1.5 × ULN or creatinine clearance ≥50 mL/min
   * Urine dipstick protein \<2+; if baseline dipstick proteinuria is ≥2+, 24-hour urinary protein must be \<1 g
   * International normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤1.5 × ULN

Exclusion Criteria:

1. Histopathological exclusions

   * Mixed HCC subtypes: Fibrolamellar HCC or sarcomatoid HCC or cholangiocarcinoma components
2. Curative local therapy candidacy

   * Current candidacy for resection, liver transplant, or RFA
3. RT infeasibility

   * Prior radioembolization
   * Single liver tumor ≥15 cm or total intrahepatic tumor diameter ≥20 cm
   * more than 5 discrete intrahepatic parenchymal foci are present
   * direct tumor extension into the stomach, duodenum, small bowel, or large bowel
   * measurable common or main-branch biliary duct involvement
   * Prior liver radiotherapy that would result in excessive overlap with the planned treatment fields
4. Prior systemic therapies

   * Received targeted-immunotherapy for HCC (e.g., PD-(L)1 inhibitors + tyrosine kinase inhibitors (TKIs))
   * Prior immunotherapy: anti-PD-(L)1/CTLA-4 or chimeric antigen receptor T-cell therapy
5. Hemorrhage/portal hypertension and hepatic decompensation risk

   * Variceal bleeding within 6 months.
   * Untreated or high-risk esophagogastric varices (e.g., grade ≥2 on endoscopy within 3 months) or other clinical evidence of portal hypertension with high bleeding risk per investigator.
   * Moderate or severe ascites
   * History of or active hepatic encephalopathy
   * History of hemoptysis (≥2.5 mL of bright red blood per episode) within 28 days before study treatment
   * Evidence of bleeding diathesis or significant coagulopathy
   * Current or recent (within 10 days before study treatment) use of aspirin (≥325 mg/day), dipyridamole, ticlopidine, clopidogrel, cilostazol, or therapeutic-dose oral/parenteral anticoagulants or thrombolytic agents
6. Allergy to any component of iparomlimab/tuvonralimab or bevacizumab
7. Comorbidities

   * Active autoimmune disease or a history of autoimmune or inflammatory disease that may relapse; exceptions include hypothyroidism controlled with hormone replacement only, controlled celiac disease, and skin disorders not requiring systemic treatment (e.g., vitiligo, psoriasis, or alopecia)
   * Any condition requiring systemic corticosteroids (\>10 mg/day prednisone or equivalent) or other immunosuppressive medication within 14 days before study treatment
   * Active or uncontrolled infection, including tuberculosis, or known HIV infection
   * Prior allogeneic stem cell transplantation or organ transplantation
   * Inadequately controlled hypertension, defined as systolic blood pressure ≥150 mmHg and/or diastolic blood pressure \>90 mmHg despite optimal medical management, or a history of hypertensive crisis or hypertensive encephalopathy
   * History within 6 months before study treatment of myocardial infarction, unstable angina, symptomatic heart failure (New York Heart Association class ≥II), cerebrovascular accident, transient ischemic attack, pulmonary embolism, deep vein thrombosis, or other serious thromboembolic events
   * Major surgical procedure within 28 days before study treatment, or serious, non-healing or dehiscing wound, active ulcer, or untreated bone fracture
   * History within 6 months before study treatment of gastrointestinal perforation, abdominal or tracheoesophageal fistula, or intra-abdominal abscess