Potential implications on TCP for external beam prostate cancer treatment when considering the bystander effect in partial exposure scenarios

Abstract

The bystander model, when applied to clinically relevant scenarios, demonstrates the potential to deviate from the TCP predictions of the common local LQ model when sub-volumes of a target volume are randomly or systematically missed over a course of fractionated radiation therapy.

The relative biological effectiveness of out-of-field dose

“…Bystander effects have been shown in many different experiments, and these effects are well documented (Nagasawa and Little 1992, Prise and O'Sullivan 2009, Ebert et al 2010, Balderson and Kirkby 2014, Balderson and Kirkby 2015. Bystander effects seem to challenge the fundamental assumption of the prevalent LQ model (i.e.…”

“…Radiation induced bystander effects cause cells to respond to the fact that neighboring cells have been irradiated (Prise and O'Sullivan 2009) and therefore do not necessarily respond to radiation dose in isolation (Balderson andKirkby 2014, Balderson and. Bystander effects are assumed to result from with cell-cell communication through gap junction intercellular communication (GJIC) or through signals released in to the surrounding medium (Denning et al 1997, McMasters et al 1998.…”

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

“…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.…”

Cellular signalling effects in high precision radiotherapy

“…Recent mathematical analysis has suggested that intercellular communication may play a significant role in cell death even in populations exposed to doses up to several Gray (Ebert et al 2010, Blyth and Sykes 2011, McMahon et al 2013a, Balderson and Kirkby 2014. This is potentially very important for radiotherapy planning, as any dependence of in-target cell killing on out-of-field dose would conflict with the goal of minimising exposure of healthy tissue.…”