Anne E. Kiltie (United Kingdom)
University of Oxford Department of OncologyAuthor Of 1 Presentation
INVESTIGATING THE IMPORTANCE OF TEMPORAL PULSE STRUCTURES FOR THE FLASH SPARING EFFECT OF ACUTE NORMAL TISSUE TOXICITY IN THE MURINE GASTROINTESTINAL SYSTEM
Abstract
Background and Aims
Radiation-induced gastrointestinal toxicity is a dose-limiting factor in radiotherapy. Recent preclinical studies have shown in multiple models that irradiation at ultra-high dose rates (FLASH) reduces normal tissue toxicity compared to irradiation at conventional dose rates. Here we used a 6 MeV electron LINAC to study acute normal tissue toxicity in C3H mice, where the whole abdomen was irradiated to various radiation doses with FLASH irradiation (mean dose rate = 2-6 MGy/s) or conventional dose rate irradiation (mean = 15 Gy/min). Subsequently, the importance of the temporal pulse structure for the FLASH sparing effect was investigated by varying the number of pulses and the different time interval between two pulses.
Methods
Mice were weighed daily and culled 3.75 days after irradiation and the gastrointestinal systems collected for histological assessment. Stools were collected one day before mice culling to assess the gastrointestinal functionality. Normal tissue damage was quantified using a modified Swiss roll-based crypt assay. Whole blood and plasma were also collected for immunological assessment.
Results
Compared to conventional irradiation, FLASH irradiation showed a dose modifying factor of ≈1.1(a 10% higher dose was required for FLASH irradiation to cause the same level of acute toxicity as conventional dose rate irradiation). Mice irradiated with FLASH also showed reduced weight loss compared to mice that received conventional irradiation. Overall, the normal tissue sparing effect seen in our study seemed to be primarily governed by the mean dose rate.
Conclusions
This study further demonstrates the clinical potential of FLASH radiotherapy, with its capacity of sparing gastrointestinal normal tissue.