Abstract
Synchrotron facilities produce ultra-high dose rate X-rays that can be used for selective cancer treatment when combined with micron-sized beams. Synchrotron microbeam radiation therapy (MRT) has been shown to inhibit cancer growth in small animals, whilst preserving healthy tissue function. However, the underlying mechanisms that produce successful MRT outcomes are not well understood, either in vitro or in vivo. This study provides new insights into the relationships between dosimetry, radiation transport simulations, in vitro cell response, and pre-clinical brain cancer survival using intracerebral gliosarcoma (9LGS) bearing rats. As part of this ground-breaking research, a new image-guided MRT technique was implemented for accurate tumor targeting combined with a pioneering assessment of tumor dose-coverage; an essential parameter for clinical radiotherapy. Based on the results of our study, we can now (for the first time) present clear and reproducible relationships between the in vitro cell response, tumor dose-volume coverage and survival post MRT irradiation of an aggressive and radioresistant brain cancer in a rodent model. Our innovative and interdisciplinary approach is illustrated by the results of the first long-term MRT pre-clinical trial in Australia. Implementing personalized synchrotron MRT for brain cancer treatment will advance this international research effort towards clinical trials.
Highlights
In the last 30 years, treatment outcomes for brain cancer in children and young adults have remained at a stand-still
The major difference between the conventional kilovoltage and synchrotron therapies is the rate at which dose is delivered, as mean energies are comparable
Cellular dose rate dependence is seen with FLASH radiotherapy[39], in favor of normal tissue protection and with equivalent tumor responses
Summary
In the last 30 years, treatment outcomes for brain cancer in children and young adults have remained at a stand-still. Due to the extremely invasive nature of high-grade brain cancers, treatments remain challenging and research into novel therapies with improved outcomes are still needed. Synchrotron microbeam radiation therapy (MRT) is an innovative cancer treatment technique proposed in 19924. The synchrotron radiation source is extremely brilliant and non-divergent, capable of producing a high-flux of photons leading to irradiation dose-rates upwards of thousands of Gray (Gy) per second[5]. The synchrotron microbeam array contains micron-sized beamlets that promote radiosurgical treatment of cancers (with in-beam, or peak doses, of hundreds of Gray). Numerous pre-clinical studies support the reduction in normal tissue damage with MRT, while effectively treating the cancer[5–8]. Amongst the synchrotron facilities that provide the technical pre-requisites to explore MRT, there is significant variation between treatment techniques including beam dimensions and spacing, beam filtration, image guidance, dose rates and doses. Studies[4,9–12] use skin entrance doses as a standard, providing insufficient knowledge of the
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