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.
Highlights
The development of new radiotherapy (RT) beam delivery techniques, e.g., laser driven particle acceleration [1], micro beam RT [2] or ultra-high dose rate irradiation (FLASH) [3], is a long-term process, where the general concept should be proven early on, even though clinical requirements, such as a stable dose delivery, are not yet fulfilled
For the statistical analysis of the corresponding data, it is important to apply methods that allow for the inclusion of data points with deviations in dose delivery
Growth data from xenograft subcutaneous tumours were obtained for dedicated, power to reveal a significant difference between the beam qualities
Summary
The development of new radiotherapy (RT) beam delivery techniques, e.g., laser driven particle acceleration [1], micro beam RT [2] or ultra-high dose rate irradiation (FLASH) [3], is a long-term process, where the general concept should be proven early on, even though clinical requirements, such as a stable dose delivery, are not yet fulfilled. Starting with physical optimization and in vitro experiments, a successful concept will be validated by in vivo trials before considering it for clinical application. Deviations from the prescribed dose may occur in all experiments, where pulsed radiation is applied. Compared to continuous beam delivery, the pulsed mode is most often harder to control and might result in over- or under-dosage. Another much less likely scenario is the failure of dosimetric equipment or an accidental change of beam parameters, e.g., by using wrong settings of beam current, beam filtration or treatment distance. For the statistical analysis of the corresponding data, it is important to apply methods that allow for the inclusion of data points with deviations in dose delivery
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
