A Real-world Study of Immunotherapy Combination Regimens for Treating Liver Cancer in Cold Regions

Hepatocellular carcinoma (HCC) is a common global malignancy. In China, the disease burden is substantial: HCC ranks fifth in cancer incidence and third in mortality, with a 5-year relative survival of only 14.4%. In Northeast China's cold regions, metabolic diseases such as hypertension, hyperlipidemia, and diabetes are prevalent and may influence HCC prognosis. Recently, PD-1/PD-L1 inhibitor-based combination regimens (with targeted therapy, chemotherapy, or locoregional treatment) have achieved major breakthroughs, significantly extending overall and progression-free survival. These regimens have become the first-line backbone for unresectable HCC. Investigating their real-world effectiveness and safety is critical for optimizing regional treatment strategies.

Study Overview

• Status: Active, not recruiting
• Conditions: Liver Cancer
• Intervention / Treatment: Drug: Immune Checkpoint Inhibitors

Detailed Description

This open-label, multicenter, retrospective real-world study aims to enroll 1000 patients with confirmed HCC, intrahepatic cholangiocarcinoma, or mixed cell carcinoma who have long-term residence in Northeast China (annual mean temperature 1.6°C-10°C) and have received immune-based combination therapy. Patient data will be retrospectively collected from January 1, 2020, to December 31, 2025. Based on treatment stage, patients will be assigned to 1 of 4 cohorts: perioperative (neoadjuvant/adjuvant), locoregional therapy, first-line advanced, or later-line advanced. This noninterventional study does not alter routine clinical practice; data are derived from medical records. The primary objective is to evaluate real-world effectiveness and safety of immune-based combinations. The primary endpoint is overall survival (OS). Secondary endpoints include objective response rate (rwORR), progression-free survival (rwPFS), disease control rate (rwDCR), duration of response (rwDOR), and safety (AE, SAE, irAE rates). The findings aim to provide real-world evidence for immunotherapy in HCC across Northeast China.

• Study Type: Observational
• Enrollment (Estimated): 1000

Contacts and Locations

Study Locations

• China
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150081
      • Harbin Medical University Cancer Hospital, No. 150 Haping Road, Nangang District, Harbin, Heilongjiang Province, China

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Patients with a clinically confirmed diagnosis of primary hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (iCCA), or combined hepatocellular-cholangiocarcinoma (cHCC-CCA), with measurable tumor lesions.

Description

Inclusion Criteria

1. Patients with a clinically confirmed diagnosis of primary hepatocellular carcinoma, intrahepatic cholangiocarcinoma, or combined hepatocellular-cholangiocarcinoma, with measurable tumor lesions.
2. Patients who have long-term residence in the cold regions of Northeast China, specifically in provinces with an annual mean temperature between 1.6°C and 10°C: Heilongjiang Province, Jilin Province, and selected cities in Liaoning Province.
3. Patients who have received an immune-based therapy regimen.
4. Patients with complete clinical data who meet the enrollment criteria, retrospectively collected from January 1, 2020, to December 31, 2025.

Exclusion Criteria

1. Patients with concurrent other malignancies.
2. Patients who are confirmed pregnant or breastfeeding.
3. Any other conditions that, in the investigator's judgment, make the patient unsuitable for participation in this study.

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Perioperative Therapy Cohort; Patients receiving immune-based combination therapy as neoadjuvant or adjuvant treatment.	Drug: Immune Checkpoint Inhibitors; Immunotherapy: PD-1 inhibitors (e.g., pembrolizumab, nivolumab, camrelizumab, sintilimab) and other immune checkpoint inhibitors; PD-L1 inhibitors (e.g., atezolizumab, durvalumab, adebrelimab) and other immune checkpoint inhibitors. Targeted therapy: Lenvatinib, donafenib, sorafenib, apatinib, bevacizumab, and other targeted therapy agents. Chemotherapy: Oxaliplatin-based and other systemic chemotherapy regimens. Locoregional therapy: Transarterial chemoembolization (TACE), hepatic arterial infusion chemotherapy (HAIC), radiofrequency ablation (RFA), microwave ablation (MWA), percutaneous ethanol injection (PEI), cryoablation, external beam radiotherapy (EBRT), and internal radiotherapy. Other regimens selected/recommended by investigators: Including but not limited to traditional Chinese medicine preparations and other antitumor therapies. Treatment options include immunotherapy alone, immunotherapy combined with targeted therapy, or immunotherapy combined with locoregional thera
Locoregional Therapy Combined Cohort; Patients receiving immune-based combination therapy combined with locoregional therapies such as ablation, TACE, HAIC, or radiotherapy.	Drug: Immune Checkpoint Inhibitors; Immunotherapy: PD-1 inhibitors (e.g., pembrolizumab, nivolumab, camrelizumab, sintilimab) and other immune checkpoint inhibitors; PD-L1 inhibitors (e.g., atezolizumab, durvalumab, adebrelimab) and other immune checkpoint inhibitors. Targeted therapy: Lenvatinib, donafenib, sorafenib, apatinib, bevacizumab, and other targeted therapy agents. Chemotherapy: Oxaliplatin-based and other systemic chemotherapy regimens. Locoregional therapy: Transarterial chemoembolization (TACE), hepatic arterial infusion chemotherapy (HAIC), radiofrequency ablation (RFA), microwave ablation (MWA), percutaneous ethanol injection (PEI), cryoablation, external beam radiotherapy (EBRT), and internal radiotherapy. Other regimens selected/recommended by investigators: Including but not limited to traditional Chinese medicine preparations and other antitumor therapies. Treatment options include immunotherapy alone, immunotherapy combined with targeted therapy, or immunotherapy combined with locoregional thera
First-Line Advanced Cohort; Patients with advanced HCC who have received no prior systemic therapy and receive immune-based combination as first-line treatment.	Drug: Immune Checkpoint Inhibitors; Immunotherapy: PD-1 inhibitors (e.g., pembrolizumab, nivolumab, camrelizumab, sintilimab) and other immune checkpoint inhibitors; PD-L1 inhibitors (e.g., atezolizumab, durvalumab, adebrelimab) and other immune checkpoint inhibitors. Targeted therapy: Lenvatinib, donafenib, sorafenib, apatinib, bevacizumab, and other targeted therapy agents. Chemotherapy: Oxaliplatin-based and other systemic chemotherapy regimens. Locoregional therapy: Transarterial chemoembolization (TACE), hepatic arterial infusion chemotherapy (HAIC), radiofrequency ablation (RFA), microwave ablation (MWA), percutaneous ethanol injection (PEI), cryoablation, external beam radiotherapy (EBRT), and internal radiotherapy. Other regimens selected/recommended by investigators: Including but not limited to traditional Chinese medicine preparations and other antitumor therapies. Treatment options include immunotherapy alone, immunotherapy combined with targeted therapy, or immunotherapy combined with locoregional thera
Later-Line Advanced Cohort; Patients with advanced HCC who have progressed after at least one prior systemic therapy and receive immune-based combination as subsequent treatment.	Drug: Immune Checkpoint Inhibitors; Immunotherapy: PD-1 inhibitors (e.g., pembrolizumab, nivolumab, camrelizumab, sintilimab) and other immune checkpoint inhibitors; PD-L1 inhibitors (e.g., atezolizumab, durvalumab, adebrelimab) and other immune checkpoint inhibitors. Targeted therapy: Lenvatinib, donafenib, sorafenib, apatinib, bevacizumab, and other targeted therapy agents. Chemotherapy: Oxaliplatin-based and other systemic chemotherapy regimens. Locoregional therapy: Transarterial chemoembolization (TACE), hepatic arterial infusion chemotherapy (HAIC), radiofrequency ablation (RFA), microwave ablation (MWA), percutaneous ethanol injection (PEI), cryoablation, external beam radiotherapy (EBRT), and internal radiotherapy. Other regimens selected/recommended by investigators: Including but not limited to traditional Chinese medicine preparations and other antitumor therapies. Treatment options include immunotherapy alone, immunotherapy combined with targeted therapy, or immunotherapy combined with locoregional thera

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Time from initiation of immune-based combination therapy to death from any cause	From start of treatment to death or last follow-up, assessed up to 36 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Real-World Progression-Free Survival (rwPFS)	Time from treatment initiation to first documented disease progression or death, based on real-world clinical assessment.	From start of treatment to progression or death, assessed up to 36 months.
Real-World Objective Response Rate (rwORR)	Proportion of patients with best overall response of complete response (CR) or partial response (PR) based on real-world clinical assessment.	From start of treatment to end of treatment, assessed up to 36 months.
Real-World Best Overall Response (rwBOR)	Best tumor response recorded during treatment, including CR, PR, SD, PD, or NE based on real-world clinical assessment.	From start of treatment to end of treatment, assessed up to 36 months.
Real-World Disease Control Rate (rwDCR)	Proportion of patients with best overall response of CR, PR, or stable disease (SD) based on real-world clinical assessment.	From start of treatment to end of treatment, assessed up to 36 months
Real-World Duration of Response (rwDOR)	Time from first documented CR or PR to disease progression or death, assessed in patients who achieved objective response.	From first response to progression or death, assessed up to 36 months.
AE Incidence	Incidence and severity of adverse events (AEs), serious adverse events (SAEs), and immune-related adverse events (irAEs), graded by NCI-CTCAE v6.0.	From first dose to 90 days after last dose of immunotherapy or 30 days after last dose of antiangiogenic agents, whichever is later.

Collaborators and Investigators

• Sponsor: Harbin Medical University
• Collaborators: The Second Affiliated Hospital of Harbin Medical University; China-Japan Union Hospital, Jilin University; First Affiliated Hospital of Harbin Medical University; Liaoning Cancer Hospital & Institute

Study record dates

Study Major Dates

• Study Start (Actual): May 13, 2026
• Primary Completion (Estimated): May 13, 2028
• Study Completion (Estimated): May 13, 2029

Study Registration Dates

• First Submitted: June 8, 2026
• First Submitted That Met QC Criteria: June 8, 2026
• First Posted (Actual): June 12, 2026

Study Record Updates

• Last Update Posted (Actual): June 12, 2026
• Last Update Submitted That Met QC Criteria: June 8, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Immunotherapy; Retrospective Study; Real-World Study
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Liver Neoplasms; Antineoplastic Agents, Immunological; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Therapeutic Uses; Immune Checkpoint Inhibitors
• Other Study ID Numbers: HLJ-HCC-RWS-001

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