PD-1 Inhibitor Combined With 125I Seed Implantation for Hepatocellular Carcinoma's Extrahepatic Metastasis: Efficacy and Safety

Efficacy and Safety of PD-1 Inhibitor Combined With 125I Seed Implantation in the Treatment of Extrahepatic Metastasis of Hepatocellular Carcinoma

This study aims to explore the effectiveness and safety of 125I seed implantation in the treatment of hepatocellular carcinoma (HCC) with extrahepatic metastases, and to compare the efficacy differences between PD-1 inhibitor monotherapy and the combination of PD-1 inhibitor and 125I seed implantation.

A retrospective analysis was conducted on 80 eligible patients admitted to Jiangxi Provincial Cancer Hospital from January 2018 to March 2025, with 40 patients in each group. Data including patients' basic characteristics, tumor staging, alpha-fetoprotein (AFP) levels, history of hepatitis B virus (HBV) infection, etc., were collected. Parameters of seed implantation and details of metastatic lesions were recorded.

Through regular follow-ups after treatment, the degree of pain relief (evaluated by Visual Analogue Scale, VAS), tumor control efficacy (response rate, RR; local control rate, LCR), survival outcomes (local progression-free survival, LPFS; progression-free survival, PFS; overall survival, OS) were assessed. Additionally, indicators such as blood cell analysis, liver and kidney function, and treatment-related adverse reactions were monitored, providing a clinical basis for optimizing comprehensive treatment regimens for HCC with extrahepatic metastases.

Study Overview

• Status: Completed
• Conditions: HCC - Hepatocellular Carcinoma; 125I Seeds Implantation
• Intervention / Treatment: Procedure: 125I seed implantation; Drug: PD-1 Inhibitors

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Jiangxi
    • Nanchang, Jiangxi, China, 330029
      • Jiangxi Cancer Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• (1) Diagnosis of advanced primary hepatocellular carcinoma (HCC) according to established criteria [13]; (2) Presence of ≥1 measurable extrahepatic metastatic lesions; (3) Eastern Cooperative Oncology Group (ECOG) performance status score of 0; (4) Barcelona Clinic Liver Cancer (BCLC) stage C; (5) Child-Pugh class A or B; (6) Platelet count > 75×10⁹/L; (7) Estimated life expectancy > 3 months; (8) Complete clinical data available.

Exclusion Criteria:

• (1) Poor treatment compliance or inability to cooperate with ¹²⁵I seed implantation surgery; (2) Unavoidable large bronchi or major blood vessels along the puncture pathway for seed implantation; (3) History of other primary malignant tumors (except cured non-melanoma skin cancer or in-situ carcinomas); (4) Severe cardiorenal insufficiency (e.g., New York Heart Association class III/IV heart failure or estimated glomerular filtration rate < 30 mL/min/1.73m²); (5) Incomplete clinical data or loss to follow-up before the study endpoint.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: PD-1 inhibitor combined with 125I seed implantation group (combination therapy group); The combination therapy group includes patients with hepatocellular carcinoma and extrahepatic metastases who receive PD-1 inhibitor therapy (selected based on individual patient assessment and shared decision-making) alongside 125I radioactive seed implantation targeting their extrahepatic metastatic lesions. The intervention involves percutaneous implantation of 125I seeds into accessible metastases under imaging guidance to deliver localized radiation, complemented by systemic PD-1 inhibitor administration according to standard protocols. Patients undergo regular follow-ups to monitor treatment response (e.g., tumor size, pain scores), assess safety through laboratory and imaging evaluations, and manage comorbidities (such as hepatitis B virus infection or treatment-related adverse events) to ensure personalized, comprehensive care throughout the treatment course.	Procedure: 125I seed implantation; 125I seed implantation; Drug: PD-1 Inhibitors; PD-1 inhibitors (sintilimab/teriprizumab/camrelizumab) are administered intravenously at a dose of 200 mg once every three weeks. According to the manufacturer's guidelines, the dose is reduced or discontinued based on the severity of adverse effects.
Sham Comparator: PD-1 inhibitor monotherapy group (PD-1 single-agent group); The PD-1 single-agent group includes patients with hepatocellular carcinoma and extrahepatic metastases who receive PD-1 inhibitor therapy selected through shared decision-making based on their individual clinical status, tumor characteristics, and treatment preferences. The intervention involves systemic administration of PD-1 inhibitors (e.g., pembrolizumab, nivolumab) according to standard oncological protocols, with dose and treatment schedule tailored to guidelines and patient tolerance. Patients in this group undergo regular follow-ups to assess treatment response (e.g., tumor progression via imaging, serum AFP levels), monitor safety through laboratory evaluations (blood counts, liver/kidney function), and manage comorbidities-such as chronic hepatitis B virus infection requiring antiviral prophylaxis or immune-related adverse events (e.g., pneumonitis, colitis)-to ensure safe and effective care throughout the treatment course.	Drug: PD-1 Inhibitors; PD-1 inhibitors (sintilimab/teriprizumab/camrelizumab) are administered intravenously at a dose of 200 mg once every three weeks. According to the manufacturer's guidelines, the dose is reduced or discontinued based on the severity of adverse effects.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression - free Survival (PFS)	It is the time interval from the start of treatment (initiation of PD - 1 inhibitor therapy or combination treatment) to the occurrence of tumor progression (defined by imaging criteria such as RECIST) or death from any cause, whichever comes first. Tumor progression includes the development of new lesions, increase in the size of existing lesions, or clinical deterioration indicative of disease advancement.	Eligible patients who received assigned study treatment (monotherapy/combination) between Jan 2020 and Mar 2025 were enrolled. Follow-up was measured from treatment start to first progression/death, with survival cutoff in Apr 2025 (max 62 months).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	The length of time from either the start of treatment or diagnosis until the death of the patient from any cause.	Patients who received assigned study treatment (monotherapy/combination) between Jan 2020 and Mar 2025 were enrolled. Follow - up measured from treatment start to death, with survival cutoff in Apr 2025 (max 62 months）.

Collaborators and Investigators

• Sponsor: Jiangxi Provincial Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2020
• Primary Completion (Actual): March 19, 2025
• Study Completion (Actual): March 20, 2025

Study Registration Dates

• First Submitted: April 25, 2025
• First Submitted That Met QC Criteria: May 27, 2025
• First Posted (Actual): May 28, 2025

Study Record Updates

• Last Update Posted (Actual): May 28, 2025
• Last Update Submitted That Met QC Criteria: May 27, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Hepatocellular Carcinoma; Efficacy; PD-1 Inhibitors; 125I Seed Implantation
• 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; Antineoplastic Agents, Immunological; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Immune Checkpoint Inhibitors
• Other Study ID Numbers: 2025ky159

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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