Development of enabling technologies for ultra-high dose rate and spatially fractionated radiation therapy
Date
2023-04-21
Authors
Esplen, Nolan Matthew
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Abstract
Despite the important advances that have been made in radiation therapy (RT) over recent decades, there remains an ongoing demand for treatments which are capable of widening the therapeutic window. This might be achieved, for example, by reducing the normal-tissue toxicity observed following RT with curative intent. Ultra-high dose rate (UHDR) FLASH-RT and spatially-fractionated RT (SFRT) techniques are both promising examples of emerging therapies primed to address this unmet need. Unfortunately, the technological requirements for delivering these new modalities have proven to be exceptionally demanding and a limiter to their adoption in a broader context. Therefore, innovative new strategies are required to bring these techniques into a larger number of research centers around the world and to facilitate greater mechanistic understanding ahead, and in support, of future clinical translation.
In this body of work, new technologies have been developed which facilitate the delivery, and improved accessibility, of FLASH-RT and SFRT for radiobiological research. Firstly, a multi-slit collimator design and proof-of-concept demonstrated a cost-effective means of enabling micro-beam SFRT on a commercial small-animal irradiator. Thereafter, the design and validation of an anatomically realistic, 3D-printed mouse phantom for small-animal radiobiology research was conducted. The rodent-morphic phantom provides a useful tool for simulation and dosimetric verification of complex experimental configurations in the absence of treatment planning capabilities and supports improved reliability and accuracy of pre-clinical outcomes data. Lastly, in an effort to facilitate x-ray FLASH radiobiology experiments, two different sources were functionalized for UHDR photon beam production: first, using a commercial 160 kVp X-ray tube and, secondly, through the development of a megavoltage (MV) electron-to-photon converter for a high-powered electron linear accelerator. The MV source represented a world-first 10 MeV UHDR-compatible x-ray irradiation platform which was subsequently characterized for use in a first radiobiological experiment investigating FLASH effects in normal tissue for healthy mice at the clinically-relevant treatment energy of 10 MV.
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radiotherapy, radiation, cancer, kilovoltage, megavoltage, x-rays, photons, small-animal radiotherapy, novel treatments, dosimetry, simulation, radiochromic film, targets, Monte Carlo, finite element analysis, collimator, spatial fractionation, SFRT, microbeam, ultra-high dose rates, UHDR, FLASH, accelerators, e-linac, 3D printing, phantoms, thermomechanical