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Analysing Tumour Growth Delay Data from Animal Irradiation Experiments with Deviations from the Prescribed Dose

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The development of new radiotherapy technologies is a long-term process, which requires proof of the general concept. However, clinical requirements with respect to beam quality and controlled dose delivery may… Click to show full abstract

The development of new radiotherapy technologies is a long-term process, which requires proof of the general concept. However, clinical requirements with respect to beam quality and controlled dose delivery may not yet be fulfilled. Exemplarily, the necessary radiobiological experiments with laser-accelerated electrons 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 clinical Linac electrons, 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. In the simulation study, significant differences in dose response were detected by all methods except for the conventional method, which showed the lowest power. Thereby, the alternative statistical approaches may allow for reducing the total number of required animals in future pre-clinical trials.

Keywords: tumour growth; statistical approaches; delay data; analysing tumour; growth delay; growth

Journal Title: Cancers
Year Published: 2019

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