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

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.

Applying Tissue Slice Culture in Cancer Research—Insights from Preclinical Proton Radiotherapy

“…Tumor growth delay [34], tumor regression [35], and local tumor control [13] are important experimental endpoints in translational radiation oncology research using xenografts. For conventional 2D and 3D cell culture models, these endpoints can be mimicked with cellular survival in a colony formation assay [36,37] or a spheroid control dose experiment with growth delay and regrowth analysis [38].…”

ReLaX: the Helmholtz International Beamline for Extreme Fields high-intensity short-pulse laser driver for relativistic laser–matter interaction and strong-field science using the high energy density instrument at the European X-ray free electron laser facility

“…However, the number of Free Electron Lasers in the hard X-Ray regime is limited [9] , which makes the combination of highpower lasers and FELs a unique platform of research. In combination with the EuXFEL beam, it will enable novel investigations in a wide array of areas: properties of highlyexcited solids, high energy density states of matter [10,11] , probing quantum electrodynamics effects [12][13][14] , ionization dynamics at high intensities [15] , relativistic laser plasma interaction [16] , energetic particle propagation in matter [17][18][19] , the production of secondary high-energy photon and particle radiation sources [20][21][22] for material and biological [23] and medical sciences [24] are some of the main topics.…”

New Discoveries in Radiation Science

“…In these cases, one should use statistical methods for the analysis of the outcomes, which allow the inclusion of data points with deviations in dose delivery. Using experimental and simulated tumor-growth data, Karsch et al [ 13 ] compared the biological efficacy of laser-driven and conventional clinical Linac electrons with four statistical analysis methods including the classical averaging per dose point, multivariable linear regression, Cox regression and a Monte-Carlo-based approach. The first method excludes animals with high dose deviations, while the other methods include all animals in the analysis.…”

“…The first method excludes animals with high dose deviations, while the other methods include all animals in the analysis. Although all of the approaches resulted in a comparable radiobiological efficiency, the Monte-Carlo-based method, the linear regression and Cox regression were more sensitive than the conventional method and should be used in future studies [ 13 ].…”