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.

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.

Therapy-related malignancies are a major cause of long-term mortality among childhood cancer survivors. However, it is unclear how exposure to chemo- and/or radiotherapy early in life induces carcinogenesis. My aim is to determine the mechanisms and rate-limiting steps underlying the genesis of second malignancies in childhood cancer survivors. For this, we will focus on studying the etiology of therapy-related myeloid malignancies (t-MNs). I have pioneered methods to characterize mutation accumulation in single stem cells and study clonal lineages in the human hematopoietic system. My lab is embedded in Europe’s largest childhood cancer center, providing the opportunity to apply our techniques to unique patient material. In Objective 1, we will dissect the life history of t-MN and study its cellular origin. Our key question is: Was the original t-MN clone already present before chemotherapy exposure, or generated as a consequence thereof? We will address this by tracking back clonal lineages in the hematopoietic tissue of patients using the mutations present in their second cancers. In Objective 2, we will study the mutational consequences of chemotherapy in normal hematopoietic cells of children before and after they received treatment. Our key question is: Is enhanced mutagenesis rate limiting for t-MN development? To address this, we will perform in-depth mutational analyses and in vitro validations. In Objective 3, we will determine phenotypic effects of chemotherapy on population dynamics of blood. Our key question is: how does chemotherapy affect selection dynamics and clonal composition of blood? To address this, we will integrate clonal histories and lineage contributions using somatically acquired mutations. Our unique methodology and anticipated novel insights will not contribute to improved survival of children with cancer, but also to increased fundamental knowledge on the origin of cancer.

The vision of the PMPC (“Centre of excellence for precision medicine in pediatric care”) project is to position the Children’s Clinical University Hospital (CCUH) in Latvia at the leading-edge of pediatric precision medicine research and care in Europe. Precision medicine has proven its potential to revolutionize healthcare by tailoring treatments to individual patients based on their unique genetic makeup, environment and lifestyle factors. While it has shown promise and delivers results in adult populations, its potential in pediatric care is largely untapped. Our goal is to improve pediatric patient care and outcomes by establishing a new research Centre of Excellence (CoE) at CCUH’s campus for research on and adoption of innovative precision medicine approaches in an integrated and collaborative RESEARCH +INNOVATION+CARE+EDUCATION (“R+I+C+E”) environment. To this end, CCUH will team-up with Europe’s leading institute in pediatric precision medicine: the Princess Maxima Center, The Netherlands. Maxima has an extensive precision medicine program and uses advanced translational research and treatment expertise in many areas, including CAR-T cell therapies and pediatric clinical trials. The CoE will provide an environment for transdisciplinary team science with international visibility in the field of pediatric precision medicine. The center will leverage the latest advances in genomics, cell therapies, data science, and computational biology. CCUH has secured 20 million EUR from private donors as a complementary part of funding. Together with the Horizon Europe grant, the valuable knowledge/technology transfer and active collaboration with the Maxima team, PMPC’s unique value will be brought forward resulting in benefits for patients, their caregivers, researchers, healthcare professionals and society. It will strengthen CCUH’s scientific and technological capacity in precision medicine, enabling it to attain a competitive position in this promising field.

In childhood, adolescence and young adults (CAYA), melanoma is under-studied and non-existing tailored clinical guidelines and standardized approaches lead to a very low diagnostic accuracy. The MELCAYA project aims to understand risk factors and determinants of melanoma to improve the prevention, diagnosis and prognosis of melanomas in CAYAs through a strong international consortium with experts from 10 countries in different disciplines (e.g. oncology, paediatrics, ethics, policy making), and sectors (e.g. academic centers, SMEs, hospitals, patient associations). MELCAYA will work on different approaches. 1) By integrating existing reference European cohorts and registries, studies of genetic and environmental risk factors and progression of melanoma in CAYA will be performed through different omic methods, and a novel taxonomy of CAYA melanoma will be generated. 2) MELCAYA will also develop image-based robust and trustworthy machine learning tools and a pan-European second-opinion platform for better diagnosis specifically designed for CAYA. 3) Moreover, the validation of minimally and non-invasive disruptive tools based on artificial intelligence and volatilomics detection from exhaled breath and skin will lead to earlier detection and more accurate prognosis of melanoma in CAYA. 4) Finally, through the evidence gathered, MELCAYA will design and implement public health strategies and will actively involve patients and the general population. The results of MELCAYA will maximize its impact by making its data and results accessible and re-usable through integration into UNCAN.eu. This action is part of the Cancer Mission cluster of projects on ‘‘Understanding".