The SCARLET (SCAling up early and late effects Research in Lithuanian childhood cancer survivors through Education and Twinning) proposal aims to increase scientific excellence and innovation capacity at Vilnius University Hospital Santaros Klinikos (VULSK) and its affiliated entity National Cancer Institute (NCI) by scaling up research activities in Lithuanian childhood cancer survivors (CCS). The area for twinning was defined based on the emerging importance of survivorship research due to the increasing number of CCS in Europe and identified gaps in Lithuania. The key challenges addressed in the proposal are 1) lack of data on the prevalence of CCS in Lithuania exploitable in research initiatives; 2) poor transition from paediatric to adult care depriving young CCS over the age of 18 of advantages of surveillance in a research context; 3) the need to implement innovative solutions for monitoring and prevention of early and late effects through joint research activities; 4) suboptimal competences in management and administration of large-scale research projects. Four research-intensive institutions from 4 European countries will bring to the consortium their specific expertise to address identified shortcomings. The proposal aims to build on and exploit current shared research initiatives that will be leveraged to achieve SCARLET’s goal and objectives. The twinning exercise will be implemented through secondments of Lithuanian staff to the partner premises and engagement in the research activities led by partner institutions, organisation of educational events, and participation in knowledge-of-transfer meetings. As a result of the twinning activities, VULSK and NCI will improve their research profile and reputation, international visibility, and attractiveness. The expanded networking channels will facilitate Lithuanian professionals to join international research groups focused on survivorship research ultimately improving the quality of survival in Lithuania.

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.

Over 200,000 children and adolescents are diagnosed with cancer each year globally, 50,000 in Europe and North America. While there has been improvement in survival since the 1970s, the decrease in mortality has reached a plateau – for children with poor-prognosis cancers resistant or refractory to conventional treatment, the survival is less than 25%. Therefore, there is an urgent need for new medicines to cure aggressive tumors, and to reduce the toxicity and sequelae of the treatments. Developing new drugs for children with cancer is a complicated multi-step process with many involved actors (academic researchers, pharmaceutical industry, patient advocates, regulatory authorities, …). There is a need to improve the efficiency of this process and fulfil the unmet needs of children with cancer. To achieve optimal progress, multi-stakeholder collaboration is mandatory. A lack of knowledge and understanding of regulatory processes is a major roadblock to children and adolescents accessing new and beneficial drugs.The aim of this project is to build an innovative, multi-stakeholder and structured framework with an educational program tailored to the needs of the different actors, that is sustainable in the long-term and takes advantage of the expertise and work already initiated by the ACCELERATE platform. The global objectives of the educational program are:1) To build an educational structure for strategy and regulatory science in pediatric oncology drug development that is sustainable and long-lasting, for future generations of experts to come;2) To foster and disseminate expertise and to overcome stakeholder’s working in silos and strengthen true multi-stakeholder collaboration.The educational program will be based on four pillars: P1: Course on Strategic/Regulatory Science in Paediatric Oncology Drug Development; P2: 360º Multi-stakeholder rotation; P3: ACCELERATE Research Fellowship; and P4: Online Educational Training Program.

Cancer is a leading cause of death worldwide, accounting for nearly 10 million deaths in 2020, or nearly one in six deaths. Lung and liver cancers were among the top three leading causes of cancer death in 2020 with 1.8 million and 830.000 deaths, respectively. On the other hand, soft tissue sarcomas are relatively uncommon cancers diagnosed in about 1% of all adults, but much more common in children and young adults, accounting for 7–10% of paediatric malignancies; they are an important cause of death in the 14–29 years age group. Interventional Oncology involves miniaturized instruments (biopsy needles, ablation electrodes, intravascular catheters) and minimally-invasive access, guided by imaging techniques (X-ray, ultrasound, computed tomography, magnetic resonance imaging) – to target cancer with ablative or localized drug delivery strategies. Interventional Oncology can be used as a stand-alone approach, or in combination with the other approaches (‘pillars’) to enhance treatment efficacy. While cancer survival has significantly improved over time through innovations in each individual pillar, our current understanding of cancer now leads us to an intertwining of pillars and multimodal care pathways: Interventional Oncology is uniquely suited to leverage and enhance the effects of the conventional therapy pillars, while reducing the burden on the healthcare system. IMAGIO will leverage Interventional Oncology in the clinical setting to improve the cancer survival outcomes, through minimally invasive, efficient, and affordable care. We will deliver four complete, multimodal care pathways for two of the most aggressive cancers (liver, lung) and one of the most debilitating when treated with current approaches (sarcoma): 1. Multimodal interventional imaging for fast and precise radioembolization therapy of liver cancer; 2. Multimodal ablation therapy of liver cancer; 3. Multimodal diagnosis and therapy in early-stage lung cancer; and 4. Multimodal MR-HIFU-enabled therapy for abdominal sarcoma. IMAGIO will mature the next-generation interventional imaging across the full spectrum, from pre-clinical developments to impact validation in clinical trials. Expertise on Interventional Oncology and immunotherapy will be leveraged from pioneering clinical research centres and leading industry covering the full value chain of oncological care, as well as cancer patient and professional organisations. Such synergetic partnerships will accelerate the impact of the technologies and transform the way healthcare solutions are delivered, providing access to safe, fast, and effective care. By focusing on the local delivery of therapy, IMAGIO will drive the substitution of conventional higher dose systemic alternatives or invasive surgical approaches, thereby accelerating recovery, reducing complication rates and the number of patient visits.

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).”