A four-dimensional computer simulation model of the in vivo response to radiotherapy of glioblastoma multiforme: studies on the effect of clonogenic cell density.

Tumours behave as complex, self-organizing, opportunistic dynamic systems. In an attempt to better understand and describe the highly complicated tumour behaviour, a novel four-dimensional simulation model of in vivo tumour growth and response to radiotherapy has been developed. This paper presents the latest improvements to the model as well as a parametric validation of it. Improvements include an advanced algorithm leading to conformal tumour shrinkage, a quantitative consideration of the influence of oxygenation on radiosensitivity and a more realistic, imaging based description of the neovasculature distribution. The tumours selected for the validation of the model are a wild type and a mutated p53 gene glioblastomas multiforme. According to the model predictions, a whole tumour with larger cell cycle duration tends to repopulate more slowly. A lower oxygen enhancement ratio value leads to a more radiosensitive whole tumour. Higher clonogenic cell density (CCD) produces a higher number of proliferating tumour cells and, therefore, a more difficult tumour to treat. Simulation predictions agree at least semi-quantitatively with clinical experience, and particularly with the outcome of the Radiation Therapy Oncology Group (RTOG) Study 83-02. It is stressed that the model allows a quantitative study of the interrelationship between the competing influences in a complex, dynamic tumour environment. Therefore, the model can already be useful as an educational tool with which to study, understand and demonstrate the role of various parameters in tumour growth and response to irradiation. A long term quantitative clinical adaptation and validation of the model aiming at its integration into the treatment planning procedure is in progress.