PRedictive In-silico Multiscale Analytics to support cancer personalized diaGnosis and prognosis, Empowered by imaging biomarkers Title Presenter | Organization DD/MM/YYYY This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 826494.

What is PRIMAGE? PRIMAGE is one of the largest and more ambitious European research projects in medical imaging, artificial intelligence and childhood cancer. The project is financed with 10 million euros by European Commission, 16 European institutions are participating in the consortium and has an implementation duration of 4 years. Internationally recognized researches in in-silico technologies and clinical experts in pediatric cancer are part of the staff of PRIMAGE.

What is PRIMAGE? PRIMAGE project is devoted at developing methods of computational analysis of medical images applied to child cancer. PRIMAGE proposes a cloud-based platform to support decision making in the clinical management of malignant solid tumors, offering predictive tools to assist diagnosis, prognosis, therapies choice and treatment follow up, based on the use of novel imaging biomarkers, in-silico tumor growth simulation, advanced visualization 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. The proposed data infrastructures, imaging biomarkers and models for in-silico medicine research will be validated in the application context of two pediatric cancers, Neuroblastoma (NB, the most frequent solid cancer of early childhood) and the Diffuse Intrinsic Pontine Glioma (DIPG, the leading cause of brain tumor-related death in children).

What are the tumors studied by PRIMAGE? Neuroblastoma (NB): is the most common extracranial tumor in children. Every year in Europe about 35,000 new cases of children and adolescents are diagnosed. 1 in every 300 newborns will develop cancer before reaching 20 years. In Spain, about 1,000 cases are diagnosed per year. With a median age at diagnosis of 16 months and more than 95% of cases diagnosed before age 7, neuroblastoma accounts for 8 – 10% of all cases of pediatric cancer and is characterized by its great biological heterogeneity, clinical and survival. Diffuse Intrinsic Pontine Glioma (DIPG): A very rare tumor in children having a disastrous survival (10%) despite all the used weapons and all the research underway is DIPG (or diffuse glioma of the trunk). There is no curative treatment and that radiotherapy (standard treatment) is palliative since the quality of life of the patient prevails. About 16 patients are diagnosed per year in Spain. This type of tumor represents 2.5% of all oncological children and 13% of pediatric tumors of the central nervous system (CNS).

The data 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 to European shared data infrastructures.

(Hospitals + Clinical Research Units) The PRIMAGE Consortium CLINICAL PARTNERS (Hospitals + Clinical Research Units) HULAFE: the Project Coordinator is one of the biggest public hospitals in Spain, with two departments involved: Paediatric Oncology Unit (POU) and Biomedical and Imaging Research Centre (GIBI). These units are leaders in R&D of NB and Imaging Biomarkers, respectively. CCRI: the largest clinical haemato-oncological centre for childhood cancer in Austria. The CCRI hosts 12 research groups in the areas of molecular and cellular biology, molecular genetics, genomics and epigenomics, immunology, cellular therapies and clinical research on DIPG and NB. UKOELN: Experts in paediatric oncology and clinical trials corresponding to molecular research in the field of NB and DIPG, including trials, data export, data analysis, correlation of clinical and molecular data, tumour tissue collection, and molecular analysis. UKOELN is part of the Neuroblastoma Risk Group project which is a milestone by collecting clinical data of more than 10,000 NB patients diagnosed in the US, Europe, Japan, and Germany.

(AI, Imaging Biomarkers, Big Data, Computer Models, Super Computing) The PRIMAGE Consortium TECHNICAL PARTNERS (AI, Imaging Biomarkers, Big Data, Computer Models, Super Computing) Quibim: a high-tech SME devoted to the R&D of Imaging Biomarket, offering one the most advanced platforms for quantitative analysis of Imaging Biomarkers in the cloud (Quibim Precision). Medexprim: Medexprim is an ICT SME specializing in research and big data projects in biomedical imaging. ME provides PRIMAGE the automatization in identification and extraction of large numbers of image sequences from a PACS for secondary use in research. Konstanz University: Data Analysis and Visualization Group (DVBIS) from the Department of Computer Science. World-class experts on data visualization and patterns recognitions – Visual Analytics Pisa university: Department of Translational Research and new technologies in medicine and surgery (imaging biobanks). Zaragoza University: Aragon Institute of Engineering Research: Mathematical modelling of cell behaviour from an individual cell to a collective set of cells. Development of numerical techniques for efficient multiscale simulations in tissue mechanobiology and cancer.

The PRIMAGE Consortium Sheffield University: Virtualization of the behaviour of diseases, in this case NB and DIPG tumors. They are one of the most advanced R&D units in these areas worldwide. ANSYS France: large enterprise on software for simulation. ANSYS software is used by 80% of the 50 largest biomedical companies in the world. They bring a vast experience, top technology and expertise in disease simulation and modeling. Valencia University (i3M): Institute for instrumentation for Molecular Imaging. High performance computing (HPC), grid and cloud technologies. Chemotargets: high-tech SME specialized in molecule simulation applied to pharmacology and adverse effects. Tumour evolution and treatment simulation. Cyfronet: One of the largest supercomputing and networking centers in Poland. DICE: http://dice.cyfronet.pl. Bologna University: In silico medicine technologies with particular reference for multiscale modelling. Matical Innovation: R&D project management and results exploitation experts. More than 20 large EU projects. SIOPE: The European Society for Paediatric Oncology represents all professionals working in the field of childhood cancers. With more than 1850 members across 35 European countries.

Quantitative Medical Imaging PRIMAGE approach to precision medicine Quantitative Medical Imaging Patients' Specific (diseases) Population Imaging (controls) Computer Aided Detection Structured Report Biomedical Images 2D, 3D, 4D Quantitative Structured Report Data Reduction Models & High-Dimensional Data Integrated Report Clinical/Genomic Image Preparation Computer Aided Characterization

PRIMAGE workflow

Final expected outcome To integrate and validate functional prototype of PRIMAGE cloud-based platform offering predictive tools to assist management of Neuroblastoma and DIPG paediatric cancers, from diagnosis to prognosis, therapies choice and treatment follow up, based on the use of novel imaging biomarkers, tumour growth models and advanced visualisation of predictions .

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