This paper outlines the major components and function of the technologically integrated oncosimulator developed primarily within the Advancing Clinico Genomic Trials on Cancer (ACGT) project. The Oncosimulator is defined as an information technology system simulating in vivo tumor response to therapeutic modalities within the clinical trial context. Chemotherapy in the neoadjuvant setting, according to two real clinical trials concerning nephroblastoma and breast cancer, has been considered. The spatiotemporal simulation module embedded in the Oncosimulator is based on the multiscale, predominantly top-down, discrete entity-discrete event cancer simulation technique developed by the In Silico Oncology Group, National Technical University of Athens. The technology modules include multiscale data handling, image processing, invocation of code execution via a spreadsheet-inspired environment portal, execution of the code on the grid, and the visualization of the predictions. A refining scenario for the eventual coupling of the oncosimulator with immunological models is also presented. Parameter values have been adapted to multiscale clinical trial data in a consistent way, thus supporting the predictive potential of the oncosimulator. Indicative results demonstrating various aspects of the clinical adaptation and validation process are presented. Completion of these processes is expected to pave the way for the clinical translation of the system.

Abstract

The present paper outlines the initial version of the ACGT (Advancing Clinico-Genomic Trials) -- an Integrated Project, partly funded by the EC (FP6-2005-IST-026996)I-Oncosimulator as an integrated software system simulating in vivo tumour response to therapeutic modalities within the clinical trials environment aiming to support clinical decision making in individual patients. Cancer treatment optimization is the main goal of the system. The document refers to the technology of the system and the clinical requirements and the types of medical data needed for exploitation in the case of nephroblastoma. The outcome of an initial step towards the clinical adaptation and validation of the system is presented and discussed. Use of anonymized real data before and after chemotherapeutic treatment for the case of the SIOP 2001/GPOH nephroblastoma clinical trial constitutes the basis of the clinical adaptation and validation process. By using real medical data concerning nephroblastoma for a single patient in conjunction with plausible values for the model parameters (based on available literature) a reasonable prediction of the actual tumour volume shrinkage has been made possible. Obviously as more and more sets of medical data are exploited the reliability of the model "tuning" is expected to increase. The successful performance of the initial combined ACGT Oncosimulator platform, although usable up to now only as a test of principle, has been a particularly encouraging step towards the clinical translation of the system, being the first of its kind worldwide.

No abstract

Many applications require exploration of alternative scenarios; most support it poorly. Subjunctive interfaces provide mechanisms for the parallel setup, viewing and control of scenarios, aiming to support users' thinking about and interaction with their choices. We illustrate how applications for information access, real-time simulation, and document design may be extended with these mechanisms. To investigate the usability of this form of extension, we compare a simple census browser against a version with a subjunctive interface. In the first of three studies, subjects reported higher satisfaction with the subjunctive interface, and relied less on interim marks on paper. No reduction in task completion time was found, however, mainly because some subjects encountered problems in setting up and controlling scenarios. At the end of a second, fivesession study, users of a redesigned interface completed tasks 27% more quickly than with the simple interface. In the third study we examined how subjects reasoned about multiple-scenario setups in pursuing complex, open-ended data explorations. Our main observation was that subjects treated scenarios as information holders, using them creatively in various ways to facilitate task completion.