A Retrospective Study of Safety and Efficacy of Locoregional Therapies Combined With Anti-VEGF/TKIs and Immune Checkpoint Inhibitors for All Comers of Intention-to-treat Patients With Hepatocellular Carcinoma Beyond UCSF Criteria Before Liver Transplantation

This is a single-center, retrospective cohort study aiming to evaluate the safety and efficacy of a combined treatment strategy for patients with hepatocellular carcinoma (HCC) who are beyond the UCSF criteria but intended for liver transplantation. The primary objective is to assess the outcomes of these "intention-to-treat" patients who received locoregional therapies (LRT, such as TACE or radiotherapy) in combination with systemic therapy (anti-VEGF/Tyrosine Kinase Inhibitors and Immune Checkpoint Inhibitors) as a "conversion therapy" prior to potential transplantation. This approach is distinct from traditional bridging or down-staging therapies by incorporating more aggressive systemic regimens. The study plans to enroll 300 subjects. The exposure group will include approximately 100 patients beyond UCSF criteria who received the combined conversion therapy between January 2020 and December 2024. A control group of about 200 patients who met the UCSF criteria and were directly listed for transplantation in the same period will be used for comparison. Data will be collected from medical records and the China Liver Transplant Registry (CLTR), with follow-up until December 2025.

Primary outcome measures include:

Objective Response Rate (ORR) of conversion therapy per mRECIST. Rate of successful down-staging to meet UCSF criteria.

1-, 2-, and 3-year overall survival (OS) rates of the intention-to-treat population.

Actual liver transplantation rate after successful conversion. Post-transplant 1-, 2-, and 3-year OS and recurrence-free survival (RFS) rates.

Secondary outcomes involve:

Safety profiles of both conversion therapy and subsequent transplantation. Analysis of factors influencing conversion success and treatment efficacy. Determination of an optimal washout period for Immune Checkpoint Inhibitors prior to transplantation.

The study seeks to provide high-level evidence for optimizing pre-transplant conversion strategies for advanced HCC patients currently outside standard transplant criteria.

Study Overview

• Status: Not yet recruiting
• Conditions: Liver Transplantation; Hepatocellular Carcinoma
• Intervention / Treatment: Combination product: Locoregional Therapy (LRT) + Systemic Drug Therapy

• Study Type: Observational
• Enrollment (Estimated): 300

Contacts and Locations

• Study Contact: Name: Caide Lu, Professor; Phone Number: +8613957800900; Email: lucaide@nbu.edu.cn
• Study Contact Backup: Name: Shuqi Mao, Professor; Phone Number: +8617855848257; Email: mmmaoshuqi@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

This retrospective, single-center cohort study plans to include 300 patients with HCC. All patients were managed at the study center between January 1, 2020, and December 31, 2024.

1. Beyond UCSF Criteria Cohort (n = 100): Patients with HCC tumors exceeding the UCSF transplant criteria but intended for liver transplantation. All patients in this cohort received multimodal conversion therapy, combining locoregional therapies with systemic therapy.
2. Within UCSF Criteria Cohort (n = 200): A control group of patients whose HCC tumors met the UCSF criteria at the time of listing and were directly registered for liver transplantation without receiving the aforementioned conversion therapy.

Description

Inclusion Criteria:

• Age ≥16;
• Clinical diagnosis of HCC;
• CNLC Stage I-IIIA.

Exclusion Criteria:

• Extrahepatic metastasis;
• Type IV portal vein tumor thrombus.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Beyond UCSF Criteria Cohort; HCC patients receiving conversion therapy beyond UCSF criteria	Combination product: Locoregional Therapy (LRT) + Systemic Drug Therapy; Treatment regimens, doses, and durations varied based on individual clinical decisions and are collected retrospectively.
Within UCSF Criteria Cohort; HCC patients within UCSF Criteria Cohort

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	Proportion of patients achieving a Complete Response (CR) or Partial Response (PR) according to mRECIST criteria during the conversion therapy period.	From the start of conversion therapy until the completion of therapy (assessed up to 24 months).
Successful Down-staging Rate to UCSF Criteria	Proportion of patients whose tumor burden is reduced to meet the UCSF transplant criteria after conversion therapy, based on imaging and tumor marker assessment.	From the start of conversion therapy until the date of meeting UCSF criteria or therapy termination (assessed up to 24 months).
1/2/3-year Overall Survival (OS) Rate	The proportion of patients who received conversion therapy and are still alive at 1, 2, and 3 years after the transplantation surgery, analyzed using the Kaplan-Meier method.	From the initiation of conversion therapy, assessed at 1, 2, and 3 years.

Collaborators and Investigators

• Sponsor: Ningbo Medical Center Lihuili Hospital
• Investigators: Principal Investigator: Caide Lu, Professor, Ningbo Medical Centre Lihuili Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): December 20, 2025
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): March 31, 2026

Study Registration Dates

• First Submitted: December 16, 2025
• First Submitted That Met QC Criteria: December 16, 2025
• First Posted (Actual): December 30, 2025

Study Record Updates

• Last Update Posted (Actual): December 30, 2025
• Last Update Submitted That Met QC Criteria: December 16, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular
• Other Study ID Numbers: KY2025PJ483

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: A specific plan for sharing de-identified individual participant data (IPD) from this retrospective study is under development. The final decision will depend on several factors, including but not limited to: institutional review board (IRB) approval, compliance with data privacy regulations, and the establishment of appropriate data use agreements. If shared, the data would likely include demographic, clinical treatment, tumor response, and survival outcome data to support validation of study findings. The research team is committed to evaluating the possibility of sharing data in a manner that protects participant confidentiality and contributes to scientific knowledge.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No