EDN Combined With TACE/HAIC and Second-Line Immune-Targeted Treatment Versus TACE/HAIC Alone in Locally Advanced HCC With Portal Vein Tumor Thrombosis After First-Line Therapy Failure: A Prospective, Multicenter, Randomized Controlled Trial

Inclusion criteria

• Aged 18 to 75 years (inclusive), regardless of gender.
• Diagnosis of CNLC Stage IIIa HCC with portal vein tumor thrombus (vp type 1-3) confirmed by histopathology, cytology, or imaging.
• Progression of disease after first-line systemic therapy.
• At least one measurable lesion according to RECIST 1.1 criteria.
• Child-Pugh class A or B.
• ECOG performance status of 0 to 2.
• Scheduled to undergo TACE or HAIC treatment.
• Adequate hematological, hepatic, and renal function within 14 days prior to study initiation, defined as:

White blood cell count ≥2.0×10⁹/L AND neutrophil count ≥1.0×10⁹/L. Platelet count ≥60×10⁹/L. Hemoglobin concentration ≥90 g/L. Total bilirubin ≤2.0 × upper limit of normal (ULN). Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤5 × ULN. Albumin ≥2.8 g/dL. International normalized ratio (INR) ≤1.6. Creatinine ≤1.5 × ULN AND calculated creatinine clearance ≥30 mL/min.

Exclusion criteria

• Preoperative abdominal CT or MR enhanced scan suggests celiac trunk anatomy is unsuitable for EDN procedure.
• History of orthostatic hypotension.
• Diffuse liver tumors or extensive extrahepatic metastases with an expected survival of <3 months.
• Cachexia or multi-organ failure.
• Severe hepatic dysfunction (Child-Pugh class C).
• Uncorrectable coagulation dysfunction.
• Presence of severe concurrent infection.
• Accompanied by Vp4 type portal vein tumor thrombus.
• Abnormal blood supply to the target lesion that precludes transarterial interventional therapy.
• History of bilioenteric anastomosis within the past year.
• Severe allergy to known contrast agents or embolization materials.
• Pregnant or lactating women, or individuals with childbearing potential planning pregnancy during the trial period.
• Clinically significant (e.g., active) cardiovascular disease, including:

Unstable angina within ≤6 months prior to randomization. New York Heart Association (NYHA) class ≥II congestive heart failure. Poorly controlled arrhythmia despite medication (patients with controlled atrial fibrillation are eligible), or any clinically significant abnormality found on resting ECG.

≥Grade 3 peripheral vascular disease (e.g., symptomatic and interfering with activities of daily living, requiring intervention).

Transient ischemic attack or subarachnoid hemorrhage within 6 months prior to randomization, or participation in other drug or device clinical trials within 3 months.

• History of other malignancies within the past 5 years or concurrent other malignancies.
• Any other condition deemed by the investigator as unsuitable for participation in this study.