MONALISA: A SIOPEN pragmatic clinical trial to MOnitor NeuroblastomA relapse with LIquid biopsy Sensitive Analysis

MONALISA：一项 SIOPEN 实用临床试验，通过液体活检监测神经母细胞瘤复发 敏感性分析

• 批准号: 10103126
• 金额: $ 41.82万
• 依托单位: UNIVERSITY OF LEEDS
• 依托单位国家: 英国
• 项目类别: EU-Funded
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=10103126
• 关键词: MONALISA; SIOPEN; pragmatic; clinical; trial

High-risk neuroblastoma accounts for 15% of cancer related-deaths in children. Half of the >1500 patients yearly diagnosed with neuroblastoma in the EU have high-risk disease, which will relapse or progress in half these cases after first-line treatment. Relapsed neuroblastoma is aggressive and often therapy-resistant. Monitoring for disease relapse and therapy response is crucial for the survival chance of these patients. The current standard-of-care for monitoring are imaging technologies and bone marrow assessment, which are costly, invasive and a burden for children, who often require anesthesia. These drawbacks limit how often is monitored. More sensitive, less invasive and less toxic monitoring techniques are needed. The mutational spectrum often changes in recurring tumors, which may explain therapy resistance and provide additional druggable targets. Imaging, however, provides no information about molecular characteristics. Liquid biopsy tests are minimally invasive, allow frequent sampling and sensitively detect tumor molecular markers in tumor-derived DNA and messenger RNA circulating in peripheral blood. MONALISA aims to close existing gaps and establish liquid biopsies as standard-of-care to monitor relapsed/refractory neuroblastoma, as a blueprint for other pediatric cancers. Reliable, early assessment of molecular progression or relapse is the main aim of the pragmatic randomized clinical trial proposed in MONALISA. We develop a digital decision support tool to help oncologists use the new monitoring and apply patient-reported outcomes to integrate patient viewpoints and assess the effect of minimally invasive, liquid biopsy diagnostics on quality of life. We will establish whether events can be detected earlier using liquid biopsy monitoring, and whether better overall survival is enabled by earlier diagnosis and treatment interventions. This essential step towards personalized medicine will support reliable disease monitoring under treatment. “This action is part of the Cancer Mission cluster of projects on ‘‘Diagnostics and Treatment (diagnostics).”

高危神经母细胞瘤占儿童癌症与死亡的15％。在欧盟中，每年被诊断为神经母细胞瘤的> 1500例患者中有一半患有高风险疾病，这将在一线治疗后将这些病例中的一半转移或进展。复发的神经母细胞瘤是侵略性的，通常是耐治疗的。监测疾病缓解和治疗反应对于这些患者的生存机会至关重要。当前用于监测的护理标准是成像技术和骨髓评估，这些评估是昂贵，侵入性和燃烧的儿童，他们通常需要麻醉。这些缺点限制了监视的频率。需要更敏感，侵入性较小，毒性较少的监测技术。突变光谱经常在复发性肿瘤中发生变化，这可能解释了治疗耐药性并提供其他可药物靶标。然而，成像没有提供有关分子特征的信息。液体活检测试是微创的，允许经常进行采样，并在外周血中的肿瘤衍生DNA和Messenger RNA循环中敏感地检测肿瘤分子标记。 Monalisa旨在弥合现有差距，并建立液体活检作为护理标准，以监测传递/难治性神经母细胞瘤，作为其他儿科取消器的蓝图。可靠的，早期评估分子进展或缓解是莫利萨（Monalisa）提出的务实随机临床试验的主要目的。我们开发了一种数字决策支持工具，以帮助肿瘤学家使用新的监测，并将患者报告的结果应用于综合的患者观点，并评估微创，液体活检诊断对生活质量的影响。我们将确定是否可以使用液体活检监测以及是否可以通过较早的诊断和治疗干预措施来提前检测到事件。个性化医学的基本步骤将支持治疗下可靠的疾病监测。 “此行动是'诊断和治疗（诊断）项目的癌症任务集群的一部分。