A Multicenter Study on the Heterogeneity of Symptom Clusters and the Underlying Mechanisms of Gut Microbiota and Metabolites Among Childhood Cancer Survivors
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 600
- 试验地点
- 1
- 主要终点
- Symptom Cluster Severity and Structure in Childhood Cancer Survivors
研究概览
简要总结
Advances in medical care have significantly improved survival among children with cancer. In China, the 5-year survival rate has reached 71.9%. Despite these improvements, many survivors continue to experience multiple co-occurring symptoms, such as fatigue, pain, sleep disturbance, and depression, which may adversely affect their quality of life.
These symptoms often occur together as symptom clusters and may reflect shared underlying biological mechanisms. This study aims to characterize symptom clusters among childhood cancer survivors and to explore their potential biological basis.
Participants will complete questionnaire assessments at multiple time points to evaluate symptom patterns and changes over time. In addition, stool samples will be collected to analyze gut microbiota composition and metabolite profiles. The study will examine the associations between symptom clusters and gut microbiota-metabolite features.
Findings from this study are expected to improve understanding of symptom burden in childhood cancer survivors and to provide evidence for the development of targeted symptom management strategies.
详细描述
Background
Advances in diagnostic and therapeutic strategies have markedly improved survival among children with cancer. In high-income regions, the 5-year net survival rate for common childhood cancers has reached 80% to 95%, while in China the overall 5-year relative survival rate is approximately 71.9%. As survival improves, the number of childhood cancer survivors (CCS) continues to increase. However, the long-term impact of cancer and its treatment remains substantial.
Cancer treatments, including chemotherapy, radiotherapy, surgery, and targeted immunotherapy, may lead to a wide range of persistent physical and psychological symptoms. CCS often experience multiple concurrent symptoms, such as fatigue, pain, sleep disturbance, depression, and nausea. These symptoms frequently co-occur and interact, forming symptom clusters that may exacerbate overall symptom burden and negatively affect treatment outcomes, health-related quality of life, and long-term prognosis.
Symptom clusters have been widely reported across different cancer types and treatment stages. Despite observed heterogeneity, core symptom clusters-particularly physical, gastrointestinal, and psychological clusters-demonstrate relative stability across studies and over time. Longitudinal evidence suggests that while the number and composition of symptom clusters may vary, core clusters persist across treatment phases, indicating potential underlying biological mechanisms.
In addition to psychosocial factors, emerging evidence highlights the role of the gut microbiota and its metabolites in influencing host physiology and symptom expression. The gut microbiota interacts with the host through metabolic, immune, and neuroendocrine pathways, and may contribute to symptom heterogeneity via interconnected systems such as the gut-brain axis. Chemotherapy-induced inflammation and intestinal barrier disruption may further mediate these processes, suggesting a potential biological basis for persistent symptom clusters in CCS.
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
- 8 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •for Children:
- •Aged 8-18 years;
- •Clinically and pathologically confirmed diagnosis of cancer (including leukemia, lymphoma, central nervous system tumors, or other common solid tumors);
- •Currently in the rehabilitation/maintenance phase or completed treatment ≥6 months prior to enrollment;
- •No cognitive impairment; able to understand, communicate, and complete questionnaires independently;
- •Written informed consent/assent obtained from participants and their legal guardians.
排除标准
- •for Children:
- •Presence of severe treatment-related sequelae (e.g., significant organ dysfunction or neurological impairment) that may interfere with symptom assessment;
- •Poor compliance or inability to independently complete interviews/questionnaires;
- •Concurrent participation in other interventional clinical trials that may influence study outcomes;
- •Planned major surgery or initiation of new chemotherapy/radiotherapy during the study period.
- •Inclusion Criteria for Caregivers:
- •Primary caregiver of an eligible CCS participant;
- •Aged ≥20 years;
- •Able to understand study content and complete questionnaires, with adequate literacy and communication ability;
- •Written informed consent provided prior to participation.
- •Exclusion Criteria for Caregivers:
- •Experience of major adverse life events within the past 6 months (e.g., bereavement, divorce) that may affect psychological assessment
- •Presence of severe cognitive impairment;
- •Presence of severe aphasia, psychiatric disorders, or other conditions preventing independent completion of assessments.
研究组 & 干预措施
Childhood Cancer Survivors and Their Primary Caregivers
This cohort includes children aged 8-18 years diagnosed with cancer (leukemia, lymphoma, CNS tumors, or common solid tumors) who have completed active treatment or are in maintenance/recovery for ≥6 months. Eligible children must have normal cognitive and communication abilities. Primary caregivers are adults aged ≥ 20 years who provide main care and can complete assessments. Exclusion criteria include severe treatment-related complications, cognitive or communication impairments, inability to complete study procedures independently, recent major life events for caregivers, or concurrent interventions affecting outcomes. No interventions are applied; this is an observational study. Data collection includes repeated symptom assessments and stool sample analysis to explore gut microbiota and metabolite associations with symptom clusters.
结局指标
主要结局
Symptom Cluster Severity and Structure in Childhood Cancer Survivors
时间窗: Baseline, 3 months, and 6 months after enrollment
Symptom clusters will be assessed using validated patient-reported outcome instruments measuring fatigue, pain, sleep disturbance, depression, and related symptoms. Latent growth mixture modeling and network analysis will be used to identify cluster structures, severity levels, and longitudinal trajectories. Higher scores indicate greater symptom burden and more severe clustering patterns.
次要结局
未报告次要终点