Impact of Emotional Disorders on Response to Immune Checkpoint Inhibitor Therapy in Liver Cancer: A Multicenter, Prospective, Multi-Cohort Study
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Sponsor
- Tongji Hospital
- Enrollment
- 651
- Locations
- 1
- Primary Endpoint
- Progression-free survival(PFS)
Study Overview
Brief Summary
Hepatocellular carcinoma (HCC) carries a poor prognosis, with limited efficacy from current therapies including immune checkpoint inhibitors (ICIs). Concurrently, emotional distress (ED) is highly prevalent in cancer patients and is implicated in tumor progression via neuroendocrine-immune axis dysregulation (e.g., HPA axis activation, immunosuppressive TME). Emerging evidence, particularly from lung cancer, suggests ED may adversely impact ICI efficacy. However, its specific role and clinical significance in HCC, especially regarding ICI response, remain poorly understood.
To address this gap, we propose a large-scale, prospective, multicenter, multi-cohort study to systematically evaluate the impact of ED on treatment outcomes in HCC patients receiving immunotherapy.
Detailed Description
Hepatocellular carcinoma (HCC) carries a poor prognosis, with limited efficacy from current therapies including immune checkpoint inhibitors (ICIs). Concurrently, emotional distress (ED) is highly prevalent in cancer patients and is implicated in tumor progression via neuroendocrine-immune axis dysregulation (e.g., HPA axis activation, immunosuppressive TME). Emerging evidence, particularly from lung cancer, suggests ED may adversely impact ICI efficacy. However, its specific role and clinical significance in HCC, especially regarding ICI response, remain poorly understood.
To address this gap, we propose a large-scale, prospective, multicenter, multi-cohort study to systematically evaluate the impact of ED on treatment outcomes in HCC patients receiving immunotherapy.
This multi-cohort study comprises three independent cohorts:
Cohort 1: Impact of ED on first-line therapy for advanced, unresectable HCC (n=243).
In the recently published LEAP-012 study, the median progression-free survival (PFS) for advanced HCC receiving first-line transarterial chemoembolization (TACE) combined with immunotherapy and targeted therapy was 14.6 months. Based on an observed median PFS of 14.6 months for the overall population, a hazard ratio (HR) for tumor progression of approximately 1.7 for the ED group, and an estimated ED prevalence of 48.89%, we assumed exponential survival distributions for both groups. The overall survival function was constructed as:
Study Design
- Study Type
- Observational
- Observational Model
- Cohort
- Time Perspective
- Prospective
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Age between 18 and 75 years, inclusive, regardless of gender.
- •Presence of at least one radiologically measurable lesion according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (defined as a lesion with a longest diameter of ≥10 mm on CT scan).
- •Newly diagnosed, treatment-naïve patients with hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (ICC).
- •Child-Pugh liver function score ≤
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Absence of severe organic diseases affecting the heart, lungs, brain, or other major organs.
Exclusion Criteria
- •History of other malignancies.
- •Recurrent HCC.
- •Prior systemic therapy for HCC.
- •Hepatic decompensation.
- •History of severe psychiatric disorders.
- •Current use of antidepressant or anxiolytic medication.
- •Inability to comprehend or complete the assessment questionnaires.
Arms & Interventions
Advanced unresectable HCC cohort
Cohort 1: Impact of ED on first-line therapy for advanced, unresectable HCC (n=243)
Intervention: Scale score (Other)
Advanced unresectable ICC cohort
Cohort 2: Impact of ED on first-line therapy for advanced, unresectable intrahepatic cholangiocarcinoma (ICC) (n=175)
Intervention: Scale score (Other)
Resectable high-risk HCC cohort
Cohort 3: Impact of ED on postoperative recurrence in resectable high-risk HCC (n=233)
Intervention: Scale score (Other)
Outcomes
Primary Outcomes
Progression-free survival(PFS)
Time Frame: From date of enrollment until the date of first progress or date of death from any cause, whichever came first, assessed up to 60 months.
In the three cohorts, PFS following immunotherapy was compared between primary liver cancer patients with and without emotional disorders.
Secondary Outcomes
- Overall survival(OS)(From date of enrollment until the date of death from any cause, assessed up to 96 months.)
Investigators
Wan-Guang Zhang
Professor
Tongji Hospital