Impact of Emotional Disorders on Response to Immune Checkpoint Inhibitor Therapy in Liver Cancer: A Multicenter, Prospective, Multi-Cohort Study
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 651
- 试验地点
- 1
- 主要终点
- Progression-free survival(PFS)
研究概览
简要总结
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.
详细描述
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:
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Advanced unresectable HCC cohort
Cohort 1: Impact of ED on first-line therapy for advanced, unresectable HCC (n=243)
干预措施: Scale score (Other)
Advanced unresectable ICC cohort
Cohort 2: Impact of ED on first-line therapy for advanced, unresectable intrahepatic cholangiocarcinoma (ICC) (n=175)
干预措施: Scale score (Other)
Resectable high-risk HCC cohort
Cohort 3: Impact of ED on postoperative recurrence in resectable high-risk HCC (n=233)
干预措施: Scale score (Other)
结局指标
主要结局
Progression-free survival(PFS)
时间窗: 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.
次要结局
- Overall survival(OS)(From date of enrollment until the date of death from any cause, assessed up to 96 months.)