A Computational Model of Cellular Response to Modulated Radiation Fields

Modelling responses to spatially fractionated radiation fields using preclinical image-guided radiotherapy

“…As previously reported, at this dose, 16 intercellular communication drives a considerable component of cell killing in low-dose regions. As a consequence, the largest difference between physical and signalling-adjusted doses across all beam sizes is in the low-dose regions, which only see negligible physical dose.…”

“…In the traditional radiobiology paradigm that cells respond independently to ionizing radiation, the large dose valleys in GRID plans are expected to significantly reduce EUD. However, applying the theoretical model presented in previous work 16,17 to different GRID treatment plans increases cell killing within the low-dose bath, which results in an increase in the EUD across the tumour. For some irradiation conditions, this can lead to an EUD which is significantly greater than that achieved by uniformly delivering dose to the tumour.…”

“…Full descriptions of the model and its validation in vitro have been previously published 16,17,25 and are briefly summarized below for completeness.…”

“…16,17 Radiobiological response parameters for the DU-145 prostate cancer cell model were used based on radiation response characteristics determined in a previous work. 17 These parameters were found to accurately reproduce the in vitro survival response described by the linear-quadratic parameters, a 5 0.115, b 5 0.026.…”

“…13 These observations have been supported by mathematical modelling studies which suggest that intercellular communication may have a significant role in cell death even in populations exposed to doses up to several Gy. [15][16][17][18] Further evidence for these effects has been obtained in small animal models, showing effects of cell signalling in vivo for both tumour 19 and normal tissue response. 20,21 However, whilst these experimental observations demonstrate the effects of intercellular communication in vivo, their role in tumour response following radiotherapy remains to be fully determined.…”