Optimizing radiotherapy protocols using computer automata to model tumour cell death as a function of oxygen diffusion processes.
Perrine Paul-GilloteauxVincent PotironGrégory DelponStéphane SupiotSophie ChiavassaFrançois ParisSylvain V CostesPublished in: Scientific reports (2017)
The concept of hypofractionation is gaining momentum in radiation oncology centres, enabled by recent advances in radiotherapy apparatus. The gain of efficacy of this innovative treatment must be defined. We present a computer model based on translational murine data for in silico testing and optimization of various radiotherapy protocols with respect to tumour resistance and the microenvironment heterogeneity. This model combines automata approaches with image processing algorithms to simulate the cellular response of tumours exposed to ionizing radiation, modelling the alteration of oxygen permeabilization in blood vessels against repeated doses, and introducing mitotic catastrophe (as opposed to arbitrary delayed cell-death) as a means of modelling radiation-induced cell death. Published data describing cell death in vitro as well as tumour oxygenation in vivo are used to inform parameters. Our model is validated by comparing simulations to in vivo data obtained from the radiation treatment of mice transplanted with human prostate tumours. We then predict the efficacy of untested hypofractionation protocols, hypothesizing that tumour control can be optimized by adjusting daily radiation dosage as a function of the degree of hypoxia in the tumour environment. Further biological refinement of this tool will permit the rapid development of more sophisticated strategies for radiotherapy.
Keyphrases
- cell death
- radiation induced
- radiation therapy
- early stage
- deep learning
- locally advanced
- endothelial cells
- electronic health record
- cell cycle arrest
- prostate cancer
- big data
- physical activity
- stem cells
- machine learning
- randomized controlled trial
- artificial intelligence
- insulin resistance
- single cell
- combination therapy
- replacement therapy
- molecular dynamics simulations