Impact of Splenectomy on the Efficacy of Targeted Therapy and Immunotherapy in Unresectable HCC Patients With Cirrhotic Portal Hypertension

Summary

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.

Conditions

• Unresectable Hepatocellular Carcinoma

Interventions

COMBINATION_PRODUCT

Splenectomy+Targeted therapy+ Immunotherapy

Eligible 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.

Sponsors & Collaborators

• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

  collaborator OTHER

• Zhongnan Hospital

  collaborator OTHER

• Renmin Hospital of Wuhan University

  collaborator OTHER

• Taihe Hospital

  collaborator OTHER

• Hubei Cancer Hospital

  collaborator OTHER

• Xiangyang Central Hospital

  collaborator OTHER

• Wuhan Central Hospital

  collaborator OTHER

• Yichang Third Renmin Hospital

  collaborator UNKNOWN

• Zhiyong Huang

  lead OTHER

Principal Investigators

• Zhiyong Huang · Tongji Hospital

Eligibility

Min Age

18 Years

Max Age

75 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2024-03-15

Primary Completion

2027-03-15

Completion

2028-03-15

Countries

• China

Study Locations