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

高危神经母细胞瘤占儿童癌症相关死亡的15%。在欧盟，每年诊断为神经母细胞瘤的1500名患者中，有一半患有高危疾病，其中一半患者在接受一线治疗后会复发或进展。复发性神经母细胞瘤具有侵袭性，且常常具有治疗耐药性。监测疾病复发和治疗反应对这些患者的生存机会至关重要。目前监测的标准护理是成像技术和骨髓评估，这是昂贵的，侵入性的，对儿童来说是一种负担，他们经常需要麻醉。这些缺点限制了监控的频率。需要更灵敏、侵入性更小、毒性更小的监测技术。突变谱在复发性肿瘤中经常发生变化，这可能解释了治疗耐药性并提供了额外的药物靶点。然而，成像不能提供有关分子特征的信息。液体活检试验具有微创性，允许频繁取样，并能灵敏地检测外周血循环中肿瘤来源的DNA和信使RNA中的肿瘤分子标记。MONALISA旨在填补现有空白，并建立液体活检作为监测复发/难治性神经母细胞瘤的标准护理，作为其他儿科癌症的蓝图。可靠、早期的分子进展或复发评估是MONALISA提出的实用随机临床试验的主要目的。我们开发了一个数字决策支持工具，以帮助肿瘤学家使用新的监测和应用患者报告的结果来整合患者的观点，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更早地检测到事件，以及早期诊断和治疗干预是否能够提高总生存率。这一迈向个性化医疗的重要一步将支持在治疗过程中进行可靠的疾病监测。这一行动是癌症使命“诊断和治疗（诊断）”项目集群的一部分。

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).”