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.

CHAIMELEON aims to set up a structured repository for health imaging data to be openly reused in AI experimentation for cancer management. An EU-wide repository will be built as a distributed infrastructure in full compliance with legal and ethics regulations in the involved countries. It will build on partner´s experience (e.g. PRIMAGE repository for paediatric cancer and the Euro-BioImaging node for Valencia population, by HULAFE; the Radiomics Imaging Archive by Maastricht University; the national repository DRIM AI France, the Oncology imaging biobank by Pisa University). Clinical partners and external collaborators will populate the Repository with multimodality (MR, CT, PET/CT) imaging and related clinical data for historic and newly diagnosed lung, prostate and colorectal cancer patients. A multimodal analytical data engine will facilitate to interpret, extract and exploit the right information stored at the Repository. An ambitious development and implementation of AI-powered pipelines will enable advancement towards automating data deidentification, curation, annotation, integrity securing and images harmonisation, the latest being of the highest importance for enabling reproducibility of Radiomics when using large multiscanner/multicentre image datasets. The usability and performance of the Repository as a tool fostering AI experimentation will be validated, including a validation subphase by other world-class European AI developers, articulated via the organisation of Open Challenges to the AI Community. A set of selected AI tools will undergo early on-silico validation in observational (non-interventional) clinical studies coordinated by leading experts in Gustave Roussy (lung cancer), San Donato (breast), Sapienza (colorectal) and La Fe (prostate) hospitals. Their performance will be assessed, including external independent validation, on hallmark clinical decisions in response to some of the currently most important clinical end points in cancer.

The ARTEMIs project aims to consolidate existing computational mechanistic and machine-learning models at different scales to deliver ‘virtual twins’ embedded in a clinical decision support system (CDSS). The CDSS will provide clinically meaningful information to clinicians, for a more personalised management of the whole spectrum of Metabolic Associated Fatty Liver Disease (MAFLD). MAFLD, with an estimated prevalence of about 25%, goes from an undetected sleeping disease, to inflammation (hepatitis), to fibrosis development (cirrhosis) and/or hepatocellular carcinoma (HCC), decompensated cirrhosis and HCC being the final stages of the disease. However, many MAFLD patients do not die from the liver disease itself, but from cardiovascular comorbidities or complications. The ARTEMIs will contribute to the earlier management of MAFLD patients, by prognosing the development of more advanced forms of the disease and cardiovascular comorbidities, promoting active surveillance of patients at risk. The system will predict the impact of novel drug treatments or procedures, or simply better life habits. The system will therefore not only serve as a clinical decision aid tool, but also as an educational tool for patients, to promote better nutritional and lifestyle behaviors. In more advanced forms of the disease, therapeutic interventions include TIPPS to manage portal hypertension, partial hepatectomy, partial or complete liver transplant. ARTEMIs will contribute to predict per- or post-intervention heart failure, building on existing microcirculation hemodynamics models. The model developers will benefit from a large distributed patient cohort and data exploration environment to identify patterns in data, draw new theories on the liver-heart metabolic axis and validate the performance of their models. The project includes a proof-of-concept feasibility study assessing the utility of the integrated virtual twins and CDSS in the clinical context.

SYNTHIA is an ambitious collaboration between public and private institutions to facilitate the responsible use of Synthetic Data (SD) in healthcare applications. The project will improve the methodological and technical aspects of SD Generation (SDG) by developing new techniques and advancing established ones for different data modalities, including genomics and imaging, to improve the generation of realistic multimodal and longitudinal data. This project will provide the research community with approaches for transparent benchmarking of alternative SDG methods for specific applications, identify and establish evaluation metrics and methodologies, and contribute to the standardisation of an evaluation assessment framework for SD. Robust evidence of SD applicability in a set of use cases across a broad spectrum of medical conditions will be crucial to demonstrate the potential of SD to accelerate data-driven solutions of equivalent quality to those derived from real patient data. Furthermore, legal and regulatory implications of SD use will be analysed with the aim of delivering an assurance framework to guide secure SD utilization in healthcare. These significant breakthroughs will be implemented through the open SYNTHIA federated platform, facilitating responsible SD use by the health research community. The platform will facilitate users´ long-term access to extensively validated, reusable synthetic datasets, as well as to SDG workflows and SD assessment frameworks. The federated infrastructure will rely on extended open-source frameworks for interoperability with other data-sharing infrastructures in the context of the European Health Data Space. A multidisciplinary collaboration of SDG developers, FAIR data experts, clinical researchers, developers of therapies and data-based tools, legal experts, socio-economic analysts, regulatory, policy advocacy, and communication experts will provide a 360º vision on how to advance healthcare applications through SD use.