What has been achieved by CHIC?

The novelty created by the large scale transatlantic CHIC project has been impressive and multifaceted. It refers to a host of aspects of fundamental (basic) science, biomedical technology and future clinical medicine related to the quantitative understanding of cancer and the patient individualized treatment optimization of the disease. An exemplary key novel characteristic of CHIC has been the large scale intercontinental cancer multimodeller hypermodelling strategy supported by cutting edge software engineering technologies. The latter enable the technologically facilitated semi-automatic creation of new patient-centred cancer hypermodels by reusing pre-existing simpler component models (or hypomodels) and combining them in several scientifically and clinically plausible ways. CHIC has exploited to the fullest the great potential of geographically distributed world leading research teams active in the fields of multiscale cancer modelling, biomedical informatics technologies and clinical medicine. Clinical medicine has served as both the driver par excellence of the entire endeavour and the ultimate envisaged end user of its outcomes.

Clinical adaptation and partial clinical validation of the innovative, integrative and multiscale CHIC cancer hypermodels concerning the paradigmatic cancer types of nephroblastoma, non small cell lung cancer, glioblastoma and prostate cancer have been conducted in full agreement with the CHIC description of work (DoW). The strict legal and ethical framework developed by the legal partners of CHIC, being in line with the European legislation, has been fully implemented and observed throughout the implementation of the project. The preliminary partial clinical validation of the developed hypemodels, largely based on retrospective imaging, histological, molecular and clinical data has demonstrated the great potential of cancer hypermodels and Oncosimulators to be viewed as candidates for clinical decision support systems (CDS) and/or cores of future in silico trial platforms. It should be noted, however, that additional retrospective validation work for the developed hypermodel and Oncosimulators is needed in order to more fully substantiate and support their “candidacy” for undergoing validation through prospective clinical trials so as to definitely assess both their clinical validity and clinical value.

In order to support the development, the execution and the multifaceted utilization of hypermodels, a host of advanced technological components were created, tested and validated. These include inter alia the Clinically Relevant Application Framework (CRAF), the Hypermodelling Editor, the Data-, Model-, In Silico Trial- and Metadata-Repositories, the model execution framework, a strategy for semantically annotating hypermodels and special visualization kits. A successful and efficient utilization of the private cloud dedicated to CHIC also took place.

Further retrospective validation of the hypermodels, following the completion of the CHIC project, will be carried out on a bilateral or small former CHIC participating organization groups basis, in accordance with the intellectual property rights framework and other provisions developed and agreed upon during the implementation of the CHIC project.

Regarding the eventual prospective clinical validation of hypermodels, certain exploratory steps have already been taken, including focused discussions initiated by the project’s assistant clinical coordinator Professor Norbert Graf within the framework of the International Society for Pediatric Oncology (SIOP). An eventually successful outcome of the further retrospective clinical validation of the hypermodels in conjunction with a number of scientifically persuasive demonstrations of the hypermodels to clinical trials funding bodies is expected to pave the way for the design of new prospective clinical trials aiming inter alia to test and validate the hypermodels and the corresponding Oncosimulators. Sustainability of the CHIC technological platform has been ensured for 1.5 years after the completion of the project.

Before their eventual prospective clinical validation, the hypermodels and the Oncosimulators developed within the framework of the CHIC project can - and in fact already - serve as research platforms for the better quantitative exploration and the understanding of the natural phenomenon and the disease of cancer as well as for educational purposes. These include inter alia the education and the training of biomedical scientists and engineers on the current accumulated quantitative multiscale biomedical knowledge related to cancer and its treatment, the training of young clinical doctors on the natural behaviour of cancer through the use of  special visualization technologies, the education and the training of cancer patients and/or their parents or custodians (in the case of children) and the education of the general public about cancer (health literacy).

The interest of the broader clinical community for the CHIC outcomes has been strong.  Representative examples of related actions include the invitation to present and demonstrate CHIC in the International Conference on Pediatric Oncology and Clinical Peditatrics (Toronto, Canada 11-13 August 2016) and the invitation made by the European Association for Clinical Pharmacology and Therapeutics  (EACPT) to the CHIC coordinator Research Professor Georgios Stamatakos to present CHIC as a keynote lecture in the EACPT2017  Conference (Prague, June 24-27 (http://www.eacpt2017.org/ ).  An invitation made by the same clinical association regarding the submission of a scholarly paper reflecting the aforementioned keynote lecture content - to be eventually published in the Clinical Therapeutics Journal with which the latter collaborates - further demonstrates the clinical interest for the achievements of the CHIC project. On top of this, a major multinational industrial organization and CHIC partner (PHILIPS) have expressed their strong interest in participating in the further validation and eventual industrial exploitation steps regarding the CHIC outcomes.

In summary, the project has fully and successfully achieved all its objectives. Of particular note is the special emphasis put on the clinical relevance of the endeavour as a response to the independent reviewers’ highly constructive and illuminating suggestions.