Currently, the combination of targeted therapy and immunotherapy is the first-line treatment for advanced hepatocellular carcinoma (HCC). However, a subset of HCC patients with severe splenomegaly, splenic hyperfunction, and esophagogastric varices due to liver cirrhosis and portal hypertension may be unable to undergo or sustain the combination therapy, ultimately missing the optimal treatment window. Prior studies have indicated that splenectomy can significantly improve liver function and hepatic reserve in cirrhotic patients. It also addresses splenic hyperfunction and reduces the risk of bleeding from esophagogastric varices by combining splenectomy with devascularization around the cardia. Additionally, splenectomy contributes to the improvement of liver fibrosis and restoration of immune function in cirrhotic patients. This study aims to elucidate the impact of splenectomy on the efficacy of combination targeted and immunotherapy in unresectable HCC patients with cirrhotic portal hypertension, particularly those with poor liver function, significant splenic hyperfunction, and severe esophagogastric varices. The research also seeks to explore whether changes in the tumor immune microenvironment before and after splenectomy can influence the effectiveness of immunotherapy. Ultimately, the goal is to provide therapeutic opportunities for this specific patient population.
Patients aged 18 to 75 years (inclusive).
No prior systemic antitumor treatment or meeting the criteria for splenectomy during treatment.
Clinical or pathological diagnosis of hepatocellular carcinoma (HCC) that is unresectable initially or has recurred after surgery.
HBV-DNA less than 1*10^5 copies/ml and undergoing antiviral therapy.
History of or concurrent active malignancy (excluding malignancies that have been cured for over 5 years or in situ cancers that can be completely cured with adequate treatment).
Presence of central nervous system metastasis or a history of brain metastasis.
History of organ transplantation.
History of surgery in the head, chest, or abdomen within the past six months.
Unresectable HCC patients with cirrhotic portal hypertension
Cohort
Prospective
Splenectomy+Targeted therapy+ Immunotherapy
Combination productEligible patients with unresectable hepatocellular carcinoma accompanied by cirrhotic portal hypertension were enrolled in the trial, and all participants underwent either open or laparoscopic splenectomy, with or without devascularization around the cardia. Starting two weeks post-surgery, patients began intravenous infusion of PD-1 monoclonal antibody, Tislelizumab, at a dosage of 200mg every three weeks. Three weeks post-surgery, patients commenced oral administration of the targeted therapy, Lenvatinib, with a dosage based on body weight: 8mg (≤60kg) or 12mg (\>60kg), once daily.
Objective Response Rate (ORR)
ORR refers to the proportion of patients whose tumors shrink to a certain amount and maintain for a certain period of time (6 weeks after first dose of Tislelizumab), including CR+PR cases. CR (complete remission): disappearance of all target lesions, PR (partial remission): reduction of the sum of the length and diameter of the baseline lesions by ≥30%
Overall Survival (OS)
OS was defined as time from diagnosis to death from any cause or the last follow-up
Progression Free Survival (PFS)
PFS refers to the time from subject enrollment to disease progression according the Response Evaluation Criteria in Solid Tumors version 1.1 (RECISTv1.1) or death
Click on the lead sponsor to view all of their trials.
Zhiyong Huang
Lead sponsor
Tongji Hospital
Sponsor institution
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Collaborator
Zhongnan Hospital
Collaborator
Renmin Hospital of Wuhan University
Collaborator
Taihe Hospital
Collaborator
Hubei Cancer Hospital
Collaborator
Xiangyang Central Hospital
Collaborator
Wuhan Central Hospital
Collaborator
Yichang Third Renmin Hospital
Collaborator
