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

Purpose: This work investigated the potential implications on tumour control probability (TCP) for external beam prostate cancer treatment when considering the bystander effect in partial exposure scenarios. Materials and methods: The biological response of a prostate cancer target volume under conditions where a sub-volume of the target volume was not directly irradiated was modelled in terms of surviving fraction (SF) and Poisson-based TCP. A direct comparison was made between the linear-quadratic (LQ) response model, and a response model that incorporates bystander effects as derived from published in vitro data by McMahon et al. in 2012 and 2013. Scenarios of random and systematic misses were considered. Results: Our results suggested the potential for the bystander effect to deviate from LQ predictions when even very small (< 1%) sub-volumes of the target volume were directly irradiated. Under conditions of random misses for each fraction, the bystander model predicts a 3% and 1% improvement in tumour control compared to that predicted by an LQ model when only 90% and 95% of the prostate cells randomly receive the intended dose. Under conditions of systematic miss, if even a small portion of the target volume is not directly exposed, the LQ model predicts a TCP approaching zero, whereas the bystander model suggests TCP will improve starting at exposed volumes of around 85%.Conclusions: 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. (authors)