Combined Transarterial Chemoembolization, Tyrosine Kinase Inhibitor/ Anti-VEGF Antibody, and Anti-PD-1/ PD-L1 Antibody as Conversion Therapy for Advanced Hepatocellular Carcinoma: a Multicenters, Real-world, Ambispective Cohort Study
The aim of this study is to the efficacy, prognosis, adverse effects, and factors for predicting therapeutic effects and clinical prognosis of combined therapy of transarterial chemoembolization (TACE), Anti-VEGF antibodies or pan-target anti-angiogenic drugs, and anti-PD-1/ PD-L1 antibody for advanced hepatocellular carcinoma which initially unsuitable for the radical therapy, including resection, transplantation, or ablation.
• Age ≥ 18 years old
• Diagnosis of HCC is according to the American Association for the Study of Liver Diseases or European Association for the Study of the Liver guidelines of HCC management;
• at least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or mRESIST criteria.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
• Hepatocellular carcinoma (HCC) was assessed as not suitable for radical resection, liver transplant, or ablation treatment after the assessment of a multidisciplinary team because either: (1) R0 resection was not feasible; (2) remnant liver volume was less than 30% in patients who did not have cirrhosis or 40% in patients with cirrhosis, or the results of an indocyanine green test were higher than 15%; (3) patients had Barcelona Clinic Liver Cancer (BCLC) stage B or BCLC stage C.
• portal vein involvement (Chen's groups A, or Cheng's type I-II) is allowed: Chen's group A1 or Cheng's type I, tumor thrombus is involved in segmental or sectoral branches of the portal vein or above; Chen's group A2 or Cheng's type II, involvement of the first branch of portal vein.
• hepatic vein invasion (VV1 to VV2) were allowed.
• Patients with extrahepatic oligometastasis is allowed: extrahepatic oligometastasis was defined as up to three metastatic lesions in up to two organs with the largest diameter of 3 cm
• Child-Pugh liver function class A-B7
⁃ No prior transplantation, TACE, or radioembolization to the liver was allowed. Prior locoregional therapies, such as surgical resection, radiotherapy, radiofrequency ablation, percutaneous ethanol injection or cryoablation, are allowed if the disease have progressed since prior treatment. Local therapy must have been completed at least 4 weeks prior to the baseline scan.
⁃ Adequate organ and marrow function, as defined below:
‣ (1) Hemoglobin ≥80 g/L (2) Absolute neutrophil count ≥1.5 ×109/L (3) Platelet count ≥50 ×109/L (4) Total bilirubin \< 51 μmol/L (5) Alanine transaminase (ALT) and aminotransferase (AST)≤5×ULN (6) Albumin ≥28 g/L (7) INR ≤1.6 (8) Serum creatinine \< 110 μmol/L 12. Time interval between TACE and systemic therapy within 7 days.