Analysing tumour growth delay data from animal irradiation experiments with deviations from prescribed dose

Abstract: The development of new radiotherapy technologies is a long-term process, which requires proving the general concept although clinical requirements with respect to beam quality and controlled dose delivery may not yet be fulfilled. Exemplarily, the necessary radiobiological experiments with laser-accelerated ion beams are challenged by fluctuating beam intensities. Based on tumour-growth data and dose values obtained in an in-vivo trial comparing the biological efficacy of laser-driven and conventional Linac electrons [2], different statistical approaches for analysis were compared. In addition to the classical averaging per dose point, which excludes animals with high dose deviations, multivariable linear regression, Cox regression and a Monte-Carlo-based approach were tested as alternatives that include all animals in statistical analysis. The four methods were compared based on experimental and simulated data. All applied statistical approaches revealed a comparable radiobiological efficacy of laser-driven and conventional Linac electrons, confirming the experimental conclusion. However, in the simulation study, significant differences in dose-response were observed by all methods except for the conventional method. Thereby, these statistical approaches may allow for reducing the total number of required animals in future pre-clinical trials.