In Silico Oncology: Building and Validating Oncosimulators and Oncosimulator Based Hypermodels as Clinical Decision Support Systems Georgios S. Stamatakos In Silico Oncology and In Silico Medicine Group, Institute of Communication and Computer Systems, School of Electrical and Computer Engineering, National Technical University of Athens, Greece & Medical School, University of Saarland, Germany https://www.in-silico-oncology.iccs.ntua.gr/ 29 Aug. 2019 G.S. Stamatakos - Lecture at the Korea Institute of Science and Technology 1
Acknowledgements Prof. Norbert Graf is greatly acknowledged for the clinical drive, the clinical positioning, the provision of • crucial clinical data and the clinical overview of the work concerning nephroblastoma modelling, an excellent Oncosimulator development paradigm. • All my collaborators at the In Silico Oncology & In Silico Medicine Group, (ISO&ISM_G) ICCS, SECE, NTUA are greatly acknowledged for their enthusiasm, commitment and hard and efficient work. Special thanks are due to : Dr D. Dionysiou, Dr V. Antipas, Dr E. Kolokotroni, Dr E. Georgiadi, Dr S. Giatili, Dr E. Ouzounoglou, Ms K. Argyri, Mr N. Christodoulou, Mr C. Antonopoulos, Mr C. Kyroudis, and Mr N. T ousert. • Prof. Uzunoglu is duly acknowledged for his crucial encouragement and support during the initial steps of the endeavour. • All partners of the 17 organizations who participated in the European Commission (EC) funded EC-US project CHIC as well all partners involved in the Oncosimulator & Hypermodelling development and their clinical adaptation and validation for the past 22 years are greatly acknowledged for their important contributions. All partners involved in the Oncosimulator development and validation of the European Commission • funded projects ACGT, ContraCancrum, TUMOR, p-medicine, Dr Tharapat, MyHealthAvatar are duly acknowledged. • All external collaborators of ISO&ISM_G since 1997 are duly acknowledged. • The European Commission, the Greek and the German States are duly acknowledged for their crucial financial support G.S. Stamatakos - Lecture at the Korea Institute of Science and 29 Aug. 2019 2 Technology
The CHIC Project at a glance G.S. Stamatakos - Lecture at the Korea Institute of Science and 29 Aug. 2019 3 Technology
The CHIC Project at a glance • The large scale EU-US integrating research project CHIC has been entitled: “ CHIC: Developing meta- and hyper-multiscale models and repositories for in silico oncology ” • Website: http://www.chic-vph.eu/ • Funded by the European Commission with a grant of 10,582,000 € . • Seventeen academic, research and industrial partner organizations across Europe and US participated in CHIC. • The CHIC project underwent its final review on 23 and 24 May 2017 and was assessed as " Excellent " by the Board of (five) External Reviewers appointed the European Commission. G.S. Stamatakos - Lecture at the Korea Institute of Science and 29 Aug. 2019 4 Technology
The CHIC Project at a glance (cont.) G.S. Stamatakos - Lecture at the Korea Institute of Science and 29 Aug. 2019 5 Technology
The CHIC Project at a glance (cont.) G.S. Stamatakos - Lecture at the Korea 29 Aug. 2019 6 Institute of Science and Technology
The CHIC Project at a glance (cont.) • THE CHIC PROJECT COORDINATION SCHEME • Overall and Scientific Coordinator : Research Professor G. Stamatakos, ICCS-National T echnical University of Athens, Greece • Assistant Clinical Coordinator : Professor Norbert Graf, University Hospital of Saarland, Germany G.S. Stamatakos - Lecture at the Korea 29 Aug. 2019 7 Institute of Science and Technology
Structure of the presentation • A brief outline of the purpose, methods and results • Examples from the methods and the results • Conclusions G.S. Stamatakos - Lecture at the Korea 29 Aug. 2019 8 Institute of Science and Technology
A brief outline of the purpose, methods and results G.S. Stamatakos - Lecture at the Korea 29 Aug. 2019 9 Institute of Science and Technology
Purpose of CHIC • to develop , clinically adapt and partly clinically validate meta- and hyper-multiscale models and repositories for in silico oncology • to develop advanced technological cloud based infrastructures supporting the process of hypermodel development and the clinical translation of hypermodels G.S. Stamatakos - Lecture at the Korea 29 Aug. 2019 10 Institute of Science and Technology
Methods • A host of clinical, experimental, mathematical, computational and software engineering strategies, methods and techniques have been devised and/or utilized in order to both develop and test multiscale hypermodels . • A hypermodel is a complex mathematical and computational model consisting of more than one elementary component model. • Each component model or “ hypomodel ” simulates a crucial biological mechanism of tumour growth and response to treatment. G.S. Stamatakos - Lecture at the Korea 29 Aug. 2019 11 Institute of Science and Technology
Methods (cont.) • Hypomodels are connected together in several ways dictated by the current biological and clinical knowledge. • Both mechanistic and machine learning based hypermodels have been developed driven by clinically relevant questions formulated by the clinical partners of the CHIC consortium. G.S. Stamatakos - Lecture at the Korea 29 Aug. 2019 12 Institute of Science and Technology
Methods (cont.) • The overarching idea of the project was to exploit the accumulated quantitative experimental and clinical knowledge concerning several spatiotemporal scales of cancer biocomplexity in order to produce treatment response predictions as precise as possible based on the patient’s individual multiscale data (e.g. – imaging – Histological – molecular, – Clinical data G.S. Stamatakos - Lecture at the Korea 29 Aug. 2019 13 Institute of Science and Technology
Methods (cont.) • To this end several candidate treatment schemes can be simulated using detailed hypermodels fed with the actual multiscale data of the patient. • The treatment scheme performing best in silico will serve as the optimal suggestion to the clinician to consider for their final treatment strategy decision. • Most hypomodels or component models have been developed by different leading cancer modelling groups participating in the CHIC project scattered across EU and US. G.S. Stamatakos - Lecture at the Korea 29 Aug. 2019 14 Institute of Science and Technology
Methods (cont.) • A clinician friendly technological pla tform for hypermodel creation and execution (CRAF) has also been developed and successfully tested. • Four paradigmatic cancer types have been considered: – nephroblastoma, – non small cell lung cancer – glioblastoma (treated with immunotharepy in conjunction with radiotherapy and chemotherapy) – prostate cancer. G.S. Stamatakos - Lecture at the Korea 29 Aug. 2019 15 Institute of Science and Technology
Results • Both the hypermodels and the technological platforms developed by CHIC have been documented, disseminated and demonstrated in real time and in detail to the appointed independent scientific evaluators of the European Commission. • The overall project outcome has been finally assessed as Excellent and worth further translational development and multifaceted exploitation. G.S. Stamatakos - Lecture at the Korea 29 Aug. 2019 16 Institute of Science and Technology
Examples from the methods and the results G.S. Stamatakos - Lecture at the Korea 29 Aug. 2019 17 Institute of Science and Technology
Dimensions of cancer manifestation and treatment G.S. Stamatakos - Lecture at the Korea 29 Aug. 2019 18 Institute of Science and Technology
The Oncosimulator: a functional diagram G.S. Stamatakos - Lecture at the Korea 29 Aug. 2019 19 Institute of Science and Technology
Basic architecture of a cancer multimodeller hypermodel G.S. Stamatakos - Lecture at the Korea 29 Aug. 2019 20 Institute of Science and Technology
Mathematics hidden behind each constituent hypomodel G.S. Stamatakos - Lecture at the Korea 29 Aug. 2019 21 Institute of Science and Technology
Nephroblastoma G.S. Stamatakos - Lecture at the Korea 29 Aug. 2019 22 Institute of Science and Technology
Nephroblastoma (Part of the whole table of diagrams / nephroblastoma ) G.S. Stamatakos - Lecture at the Korea 29 Aug. 2019 23 Institute of Science and Technology
Nephroblastoma G.S. Stamatakos - Lecture at the Korea 29 Aug. 2019 24 Institute of Science and Technology
Multiscale Cancer Modelling Paradigms G.S. Stamatakos - Lecture at the Korea 29 Aug. 2019 25 Institute of Science and Technology
The Wilms Tumour Branch of the Oncosimulator G.S. Stamatakos - Lecture at the Korea 29 Aug. 2019 27 Institute of Science and Technology
Chemotherapy treatment protocol. The simulated Wilms Tumour preoperative chemotherapy treatment protocol of the SIOP/ GPOH clinical trial. G.S. Stamatakos - Lecture at the Korea 29 Aug. 2019 28 Institute of Science and Technology
• Wilms Tumour Oncosimulator: – Tumor Free Growth - Tumor Chemotherapy G.S. Stamatakos - Lecture at the Korea 29 Aug. 2019 29 Institute of Science and Technology
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