Precision Medicine in Neurocutaneous Syndromes: Genotype-Guided Risk Stratification and Targeted Therapy Outcomes in a 20-Year Multicenter Cohort From Western China
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 1,200
- 试验地点
- 1
- 主要终点
- Progression-free survival (PFS)
研究概览
简要总结
The goal of this observational study (retrospective multicenter cohort study) is to learn if precision medicine approaches-including genetic testing, targeted drugs, and coordinated care from multiple specialists-can improve health outcomes and lower medical costs for people with neurocutaneous syndromes (NCS) in Western China, where healthcare resources are limited. NCS includes four main conditions: neurofibromatosis type 1 (NF1), tuberous sclerosis complex (TSC), Sturge-Weber syndrome (SWS), and von Hippel-Lindau disease (VHL). The main questions it aims to answer are:
- Do genetic testing and targeted drugs help people with NCS live longer without disease getting worse?
- Do these approaches better control seizures (for TSC and SWS) and shrink tumors (for NF1 and VHL)?
- Do they reduce the total cost of medical care?
Researchers will compare two groups to see the effects: participants who received precision medicine (genetic testing + targeted drugs + multidisciplinary care) versus those who received standard, uncoordinated care.
Participants will:
- Undergo genetic testing to identify specific gene changes linked to their NCS
- Receive targeted drugs (e.g., mTOR inhibitors for TSC, MEK inhibitors for NF1) if eligible
- Attend regular checkups, imaging scans (like MRI), and follow-up visits for an average of 11.4 years
- For those in the multidisciplinary care group, receive coordinated care from neurologists, geneticists, surgeons, and other specialists (with remote telemedicine visits for those living far from hospitals)
研究设计
- 研究类型
- Observational
- 观察模型
- Case Only
- 时间视角
- Retrospective
入排标准
- 年龄范围
- — 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •* Confirmed diagnosis of one of the following neurocutaneous syndromes: Neurofibromatosis Type 1 (NF1) Tuberous Sclerosis Complex (TSC) Sturge-Weber Syndrome (SWS) Von Hippel-Lindau Disease (VHL) (Diagnosis established by established clinical criteria [e.g., NIH criteria for NF1, International TSC Consensus Criteria] or confirmed pathogenic genetic variant)
- •Age between 0 and 65 years at the time of initial evaluation.
- •Follow-up duration of at least 12 months at one of the participating tertiary medical centers in Western China:
- •West China Hospital, Sichuan University (Chengdu) Xinqiao Hospital, Army Medical University (Chongqing) The First Affiliated Hospital of Xi'an Jiaotong University (Xi'an)
- •*Availability of complete baseline clinical data, including: Demographic information Diagnostic workup Initial symptom profile Treatment history (if any)
排除标准
- •Incomplete medical records- Key clinical, imaging, or genetic data missing, preventing reliable diagnosis or outcome assessment.
- •Follow-up duration less than 12 months- Patients lost to follow-up or with insufficient longitudinal data to evaluate clinical outcomes.
- •Diagnostic uncertainty- Cases that did not meet established clinical or genetic diagnostic criteria for NF1, TSC, SWS, or VHL (e.g., atypical presentations without molecular confirmation).
- •Age > 65 years at initial evaluation- Although rare in neurocutaneous syndromes, patients older than 65 were excluded to maintain cohort relevance to typical disease onset and progression patterns.
- •Participation in another interventional trial during the study period (if applicable)
研究组 & 干预措施
Multidisciplinary Care Group
patients referred to or enrolled in a structured telemedicine-supported multidisciplinary clinic, which included scheduled virtual visits via WeChat Video or DingTalk with neurologists, genetic counselors, and specialty nurses. Real-time interpretation was available for ethnic minority patients.
Standard In-Person Care (SIC) Group
Patients managed through conventional outpatient visits without structured telemedicine support.
结局指标
主要结局
Progression-free survival (PFS)
时间窗: 12 months
Proportion of patients from diagnosis to disease progression, malignant transformation, or death
Seizure control
时间窗: 12 months
Engel class I/II refers to the \*\*Engel Epilepsy Surgery Outcome Scale\*\*, a widely used classification system for assessing seizure control after epilepsy surgery. It categorizes patients into four classes based on postoperative seizure frequency: 1. \*\*Engel Class I\*\*: \*\*Seizure-free\*\* or \*\*auras only\*\* (no disabling seizures). 2. \*\*Engel Class II\*\*: \*\*Rare disabling seizures\*\* (≤3 seizure days per year). Higher Engel class (I \> II \> III \> IV) indicates better seizure control.
Tumor response
时间窗: 12 months
volumetric tumor reduction measured with preoperative tumor volume
Quality of life: SF-36 Score
时间窗: 12 months
SF-36 (Short-Form 36) is a 36-item patient-reported survey that measures generic health-related quality of life across eight domains and two summary components. Each domain is scored 0-100, where 0 = maximum disability and 100 = no disability; therefore, \*\*higher values always indicate better health\*\*. Domain structure and score range 1. \*\*Physical functioning (PF)\*\* - 0-100 2. \*\*Role-physical (RP)\*\* - 0-100 3. \*\*Bodily pain (BP)\*\* - 0-100 (higher = less pain) 4. \*\*General health (GH)\*\* - 0-100 5. \*\*Vitality (VT)\*\* - 0-100 6. \*\*Social functioning (SF)\*\* - 0-100 7. \*\*Role-emotional (RE)\*\* - 0-100 8. \*\*Mental health (MH)\*\* - 0-100
次要结局
- Overall survival Rate(12 months)
- treatment costs(12 Months)
研究者
Zhigang Lan
Professor
West China Hospital