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).”

PRIMAGE proposes a cloud-based platform to support decision making in the clinical management of malignant solid tumours, offering predictive tools to assist diagnosis, prognosis, therapies choice and treatment follow up, based on the use of novel imaging biomarkers, in-silico tumour growth simulation, advanced visualisation of predictions with weighted confidence scores and machine-learning based translation of this knowledge into predictors for the most relevant, disease-specific, Clinical End Points. PRIMAGE implements a hybrid cloud model, comprising the of use of open public cloud (based on EOSC services) and private clouds, enabling use by the scientific community (facilitating reuse of de-identified clinical curated data in Open Science) and also suitable for future commercial exploitation. The proposed data infrastructures, imaging biomarkers and models for in-silico medicine research will be validated in the application context of two paediatric cancers, Neuroblastoma (NB, the most frequent solid cancer of early childhood) and the Diffuse Intrinsic Pontine Glioma (DIPG, the leading cause of brain tumour-related death in children). These two paediatric cancers are relevant validation cases given their representativeness of cancer disease, and their high societal impact, as they affect the most vulnerable and loved family members. The European Society for Paediatric Oncology, two Imaging Biobanks and three of the most prominent European Paediatric oncology units are partners in this project, making retrospective clinical data (imaging, clinical, molecular and genetics) registries accessible to PRIMAGE, for training of machine learning algorithms and testing of the in-silico tools´ performance. Solutions to streamline and secure the data pseudonymisation, extraction, structuring, quality control and storage processes, will be implemented and validated also for use on prospective data, contributing European shared data infrastructures.

The 5-year survival for children with cancer increased from 30% in the 1970s to more than 80% at present. There are up to 300,000 childhood cancer survivors in Europe and this number is increasing. Years after treatment, childhood cancer survivors are at high risk for developing health and psychosocial late effects, resulting in excess morbidity and mortality compared the general population. The impact on the quality of life (QoL) of survivors and their families, as well as the societal and economic burdens, are significant. However, these impacts can be reduced by long-term survivorship care to detect treatable disease at an early phase and start timely interventions to preserve health, improve QoL, as well as coordinate specialised care and empower survivors. Implementing follow-up care, especially for young adult and adult survivors of childhood cancer, has proven challenging across Europe. These survivors have left paediatric care and most of them have no opportunity to visit experts in survivorship care. To improve survivorship care for these survivors across Europe, PanCareFollowUp will conduct a prospective cohort study to assess effectiveness, value, cost effectiveness and feasibility of the PanCareFollowUp Care intervention, a person-centred approach to survivor follow-up care based on international clinical guidelines for surveillance of late effects. PanCareFollowUp also includes the development and assessment of a personalised, guideline-based eHealth lifestyle intervention. Ensuring that the PanCareFollowUp interventions are used in the real world is paramount to achieving enduring improvements to survivorship care. Hence, the project includes the development of materials to support sustainable maintenance and replication of the PanCareFollowUp interventions. The PanCare network will become the guardian of the interventions after the project, ensuring that the intervention materials are openly available, sustainably maintained and widely shared.

Vilnius University Hospital Santaros Klinikos (VULSK) acts as a coordinator of the TREL (Twinning in Research and Education to improve survival in Childhood Solid Tumours in Lithuania) project that aims to enhance translational, clinical and late-effect research in paediatric solid tumours (ST). The project concept is based on the existing shortcomings in paediatric oncology at VULSK and Lithuania – scarce research indicators and inferior survival rates in children with ST. TREL has a goal to increase scientific excellence in the most common paediatric ST (brain tumours, neuroblastoma and renal tumours). VULSK and 8 leading research intensive institutions each covering different areas of the project activities according to their expertise form the TREL consortium. TREL will be delivered in 7 working packages addressing training in tumour specific laboratory research and clinical trials, cross-cutting education on genome-wide sequencing and treatment innovations, enhancing skills in observational studies on the quality of survivorship including fertility preservation and research methodology as well as project and innovation management. Training exercise will focus on the implementation of secondments of VULSK staff to the partner premises, organisation of multidisciplinary transfer-of-knowledge meetings, and participation in strategic scientific meetings corresponging objectives of each working package. As a consequence of the twinning activities with internationally-leading research active counterparts VULSK will improve its research profile and reputation, enhance international, regional and national visibility and competitiveness. Fostering of existing and establishment of new networking channels will facilitate incorporation of VULSK professionals to the ongoing collaborative projects that will improve research indicators of individual researchers and VULSK as well as will increase survival rate of children with ST in Lithuania in a long-term perspective.

Almost 500,000 former childhood cancer patients (CCS) are now living in Europe. Compared to the general population, CCS represent a vulnerable population as they are at an increased risk of developing health problems, known as late effects, resulting in excess morbidity and mortality. Many survivors are unaware of their personal risk for specific late effects, which reduces their ability to manage their own follow-up care. Similarly, their treating healthcare professionals (HCPs) lack information about care required for CCS and access to treatment data from their childhood cancer. The Survivorship Passport (SurPass) is an innovative, digital tool, developed in previous EU-funded projects, that can be used to overcome these knowledge gaps to improve people-centred long-term survivorship care. Importantly, end users (CCS, HCPs) are integral to the research, represented by three key stakeholder networks (PanCare, SIOP Europe, CCI Europe). PanCareSurPass will conduct a robust assessment of the implementation of the SurPass by first conducting a pre-implementation study in six countries (Austria, Belgium, Germany, Italy, Lithuania, Spain) representing three infrastructural scenarios in Europe. Ethical, structural, organisational, economical, national, local, privacy issues, health systems, and particular national circumstances will be taken into account throughout. An Implementation Strategy will be developed and the SurPass will be updated and validated before use in an implementation study in the six countries. The study will look at a range of outcomes including CCS activation and empowerment, CCS/HCP satisfaction with the tool, feasibility and health economics. Based on the results of the study, a Prediction Model will be developed to promote and support future implementation of the SurPass across Europe.