Research project The virtual tumour - in silico RT testbed
In silico radiotherapy testbed – from tumour modelling to effectiveness of radiation therapy evaluation.
Radiotherapy is one of the main therapeutic modalities for the treatment of cancer, more than 50% of the oncological patients being treated with this form of therapy. It succeeds in the eradication of tumours for many patients with the preservation of the vital functions of the nearby healthy organs. However, increases in the success rate of treatment are still necessary and attempts to improve (chemo)radiotherapy are continuously made through multidisciplinary projects.
In the era of virtual reality, simulation of the effect of radiation on cells, tissues and tumours aiming at better understanding the impact of biological and physical factors on the response to radiation is a natural step forward in the development of radiotherapy. Thus, recent advances in medical radiation physics, cellular and molecular tumour biology and computational simulation have provided the information and the tools for system biology approaches for cancer radiation therapy. Models with various degrees of accuracy have been proposed for describing the complexity of cancer cells and tumours and the radiobiological outcome of the interaction of radiation with these complex systems. However, accurate and versatile models for the tumours and tumour response to radiation with respect to the relevant characteristics for radiotherapy and chemo-radiotherapy are not yet available.
Furthermore, the interest in particle therapy has increased in recent years due their potential advantages with respect to dose conformation to the target and also the increased relative biological effectiveness (RBE). An increasing number of clinical centres is in operation worldwide or are currently being constructed with the purpose to investigate the clinical potential of particle therapy in the treatment of cancer. One of these centres is the Skandion Clinic, the national proton centre operated by the seven university hospitals in Sweden. The existing clinical knowledge database regarding the effectiveness of protons and ions heavier than protons is very small in comparison to the photon database and therefore it could only be used for a preliminary selection based on average expected response. In contrast, preclinical knowledge for a broad array of factors influencing proton and ion effectiveness is much larger and this could be used in a system biology approach to investigate the effectiveness of particle radiotherapy.
The overall aim of this project is to develop an in silico testbed for the simulation of the outcome of radiotherapy using photons, protons or heavier ions that would allow the investigation of the influence of various biological and physical factors on the tumour response.
The specific aims of this research project are:
• To develop in silico tumours with respect to the tumour microenviroment, intrinsic radiosensitivity and density of clonogenic cells.
• To integrate the simulated in silico tumours into a research version of a treatment planning system and simulate the effect of photon, proton and ion radiotherapy.
• To determine the relative clinical effectiveness of protons and heavier ions than protons and identify the key factors influencing the treatment outcome.
Project description
The idea of creating an in silico testbed for radiotherapy based on a virtual tumour model that would account for the main tumour microenvironmental features known to be related to the outcome of radiotherapy integrated into a treatment planning and optimisation system has a very high novelty factor, as, to the best of knowledge of the applicant, it has never been presented. The in silico investigation is extremely important as it could help designing clinical trials aiming at optimising the patient selection for different forms of radiotherapy and hence maximising the benefit for the patients by in silico assessing the relative clinical effectiveness of proton or ion radiotherapy compared to the common practice involving photon therapy,
The theoretical modelling of an in silico tumour has also the potential to identify fast the relative importance of the factors that determine the response to treatment and hence help designing the clinical trials, before or even without lengthy and costly experimental studies in animal models. Currently, many pre-clinical studies are carried out on animals on which tumours are induced and allowed to develop. An ethical question regarding the use of animals in (chemo)radiotherapy research therefore arises and consequently alternative solutions to animal experiments should always be sought. This Replacement principle of modern research has been specified together with Reduction and Refinement in the Directive 2010/63/EU on the protection of animals used for scientific purposes. In the era of virtual reality, tumour models created in silico have the potential to allow the progress in research minimising at the same time the use of animals for experiments, thus fulfilling the recommendations of Directive 2010/63/EU.
Project members
Project managers
Iuliana Livia Dasu
Professor
Members
Marta Lazzeroni
Universitetslektor
Emely Kjellsson Lindblom
Universitetslektor
