A brief overview of the completed CHIC project

May 19, 2017

In silico medicine (ISM), an emergent scientific and technological domain based on clinically driven and clinically oriented multiscale biomodelling, appears to be the latest trend regarding the translation of mathematical and computational biological science to clinical practice through massive exploitation of information technology. In silico (i.e. on the computer) experimentation for each individual patient using their own multiscale biomedical data is expected to significantly improve the effectiveness of treatment in the future, since reliable computer predictions could suggest the optimal treatment scheme(s) and schedules(s) for each separate case. Additionally, validated cancer multiscale models can serve as the basis for the development of platforms for the conduction of in silico trials. Due to the predominant manifestation of cancer at all spatiotemporal scales of biocomplexity, in silico oncology (ISO) appears to be the paradigm par excellence of in silico medicine.

The CHIC project aimed at advancing ISM through the paradigm of ISO in the following aspects: 1. Fundamental (Basic) Science (development of highly innovative clinically driven and oriented complex hypermodels and Oncosimulators by different modelling groups) 2. Information Technology (semantic description of cancer models and hypermodels, development of a secure technological infrastructure and tools and services supporting the semi-automatic accessibility, execution and reusability of models as well as the building of hypermodels) 3. Clinical Medicine (clinical drive and relevance of hypermodel building, clinical adaptation and partial clinical validation of hypermodels and Oncosimulators). The actual components developed by CHIC include a hypermodelling infrastructure consisting primarily of a hypermodelling editor, a clinical research (or clinically relevant) application framework (CRAF), a hypermodelling execution environment, an infrastructure for semantic metadata management, a hypermodel repository, a hypermodel-driven clinical data repository, a distributed metadata repository and an in silico trial repository for the storage of executed simulation scenarios. Multiscale models and data are semantically annotated using the developed ontological and annotating tools. An image processing and visualization toolkit, and cloud and virtualization services have also been developed. The CHIC tools, services, infrastructure and repositories can provide the community with a collaborative interface for exchanging knowledge and sharing work in an effective way. A number of developed features and tools enhance usability and accessibility.

In order to ensure clinical relevance and foster clinical acceptance of hypermodelling, the whole endeavour was driven by the clinical partners of the consortium. Highly innovative cancer hypermodels collaboratively developed by the consortium cancer modellers have provided, among other things, the framework and the testbed for the development of the CHIC technologies. The following four paradigmatic cancer types have been addressed: nephroblastoma, non small cell lung cancer, glioblastoma and prostate cancer. Treatment with a variety of therapeutic modalities including chemotherapy, radiation therapy, immunotherapy and hormone therapy has been considered and simulated.

Clinical adaptation and partial clinical validation of the developed hypermodels and hypermodel Oncosimulators have been successfully conducted. Further retrospective validation is now needed in order to more fully substantiate the candidacy of the CHIC hypermodels and Oncosimulators for undergoing prospective clinical trial based validation. This is a necessary step in order to definitely prove the clinical credence and the clinical value of the hypemodels and the Oncosimulators as clinical decision support systems (CDS) before an eventually large scale translation into the clinical routine.