Liquid Biopsies for the Detection of Somatic Mutations in Brain Arteriovenous Malformations
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 50
- 试验地点
- 2
- 主要终点
- Study of the diagnostic performance of 1) liquid biopsies on the artery in the immediate vicinity of the nidus, 2) liquid biopsies on the peripheral vein, for the detection of somatic genetic mutations in cAVMs
研究概览
简要总结
"Personalized medicine has revolutionized patient care, particularly in oncology. Brain arteriovenous malformations (bAVMs) are abnormal vessels located on the surface of the brain or within the brain parenchyma, causing abnormal communication between arterial and venous networks, without the interposition of the capillary bed. The main risk of these malformations is rupture, leading to intracranial bleeding, which can cause severe sequelae or even death. bAVMs (except those of clearly identified genetic origin [< 5%], such as mutations associated with Rendu-Osler disease) have long been considered non-genetic in origin.
However, somatic genetic mutations activating the RAS/RAF/MEK/ERK (MAPK) signaling pathway have recently been identified in surgical specimens of bAVMs. Additionally, targeted inhibition of this pathway is effective in treating these malformations in animals and appears to be effective in extracranial arteriovenous malformations, particularly superficial ones.
Next-generation sequencing of circulating DNA on liquid biopsies is a promising and minimally invasive approach to studying the presence of mutations in arteriovenous malformations.
The treatment of a bAVM aims to obliterate the malformation to prevent or avoid the risk of hemorrhage. It may involve several therapeutic modalities: microsurgery, endovascular embolization, and radiosurgery. These treatments can be combined, and microsurgery is often preceded by pre-surgical embolization, aimed at reducing the hemorrhagic risk of the intervention. However, these are invasive treatments, not without risk.
The identification of mutations through liquid biopsies could enable the development of non-invasive targeted therapies against these bAVMs.
This research aims to identify somatic genetic mutations activating the MAPK signaling pathway in bAVMs. These mutations have already been identified in surgical specimens. This research aims to evaluate the diagnostic performances of liquid biopsies (detection of genetic mutations in blood samples, i.e., circulating DNA), with the gold standard being the detection of the same mutations in surgical specimens."
详细描述
"Description of Domain Knowledge Personalized medicine has revolutionized patient care, especially in oncology. Brain arteriovenous malformations (bAVMs) are abnormal vessels located on the brain's surface or within the cerebral parenchyma, abnormally connecting the arterial and venous networks without the intermediary of the capillary bed. The primary risk of these malformations is rupture, leading to intracranial bleeding, which can cause severe sequelae or even death. bAVMs (excluding those of clearly identified genetic origin [< 5%], such as mutations associated with Rendu-Osler disease) have long been considered non-genetic in origin.
However, somatic genetic mutations activating the RAS/RAF/MEK/ERK (MAPK) signaling pathway have recently been identified in surgical specimens of bAVMs [1]. Moreover, targeted inhibition of this pathway is effective in treating these malformations in animal models [2] and seems effective in extracranial arteriovenous malformations, particularly superficial ones [3].
Next-generation sequencing of circulating DNA on liquid biopsies is a promising new approach, allowing for a non-invasive study of mutations in arteriovenous malformations [4].
The treatment of a bAVM aims to obliterate the malformation to prevent or mitigate hemorrhagic risk. Several therapeutic modalities can be used: microsurgery, endovascular embolization, and radiosurgery. These treatments can be combined, with microsurgery often preceded by pre-surgical embolization to reduce the hemorrhagic risk of the intervention. However, these treatments are invasive and not without risk [5].
The identification of mutations through liquid biopsies would enable the development of non-invasive targeted therapies against these bAVMs [6].
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •"_Age ≥ 18 years
- •Treated for bAVM at Pitié-Salpêtrière Hospital
- •Indication for treatment by embolization followed by surgery decided in a multidisciplinary consultation meeting (RCP) at Pitié-Salpêtrière Hospital
- •Treatment by embolization possibly followed by surgery within 24-48 hours if the embolization is incomplete
- •Informed about the study and not objecting to participation"
排除标准
- •Extra-cerebral arteriovenous malformations
- •Under legal protection (guardianship/curators, etc.)
- •Pregnancy
- •Not eligible for combined treatment (embolization followed by surgery)
结局指标
主要结局
Study of the diagnostic performance of 1) liquid biopsies on the artery in the immediate vicinity of the nidus, 2) liquid biopsies on the peripheral vein, for the detection of somatic genetic mutations in cAVMs
时间窗: 18 months
- Sensitivity / Specificity / Positive Predictive Value / Negative Predictive Value Compared with the gold standard: detection of mutations on surgical specimens
Study of the diagnostic performance of 1) liquid biopsies on the artery in the immediate vicinity of the nidus, 2) liquid biopsies on the peripheral vein, for the detection of somatic genetic mutations in cAVMs
时间窗: 30 months
\- Sensitivity / Specificity / Positive Predictive Value / Negative Predictive Value Compared with the gold standard: detection of mutations on surgical specimens
次要结局
- - Imaging characteristics of cAVMs for each of the mutations identified(18 months)
- - Prevalence of mutations on surgical specimens(18 months)
- - Prevalence of mutations on the artery in the immediate vicinity of the nidus(18 months)
- - Prevalence of peripheral vein mutations(18 months)
- - General patient characteristics for each of the mutations identified(18 months)
- - Prevalence of mutations on surgical specimens(30 months)
- - Prevalence of mutations on the artery in the immediate vicinity of the nidus(30 months)
- - Prevalence of peripheral vein mutations(30 months)
- - General patient characteristics for each of the mutations identified(30 months)
- - Imaging characteristics of cAVMs for each of the mutations identified(30 months)