Synchrotron radiation can facilitate novel radiation therapy modalities such as microbeam radiation therapy (MRT) and high dose-rate synchrotron broad-beam radiation therapy (SBBR). Both of these modalities have unique physical properties that could be exploited for an improved therapeutic effect. While pre-clinical studies report promising normal tissue sparing phenomena, systematic toxicity data are still required. Our objective was to characterise the toxicity of SBBR and MRT and to calculate equivalent doses of conventional radiation therapy (CRT). A dose-escalation study was performed on C57BLJ/6 mice using total body and partial body irradiations. Dose-response curves and TD50 values were subsequently calculated using PROBIT analysis. For SBBR at dose-rates of 37 to 41 Gy/s, we found no evidence of a normal tissue sparing effect relative to CRT. Our findings also show that the MRT valley dose, rather than the peak dose, best correlates with CRT doses for acute toxicity. Importantly, longer-term weight tracking of irradiated animals revealed more pronounced growth impairment following MRT compared to both SBBR and CRT. Overall, this study provides the first in vivo dose-equivalence data between MRT, SBBR and CRT and presents systematic toxicity data for a range of organs that can be used as a reference point for future pre-clinical work.

In MRT, spatial dose-fractionation is achieved on a microscopic scale. Fields are characterised by an array of 25 to 100 µm wide, quasi-parallel, micro-planar beams that have a centre-to-centre spacing of 100 to 400 µm [31] . This kind of array creates an inhomogeneous, periodically alternating dose profile of 'peaks'

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In this paper we use a research licensed version of the Eclipse TM treatment planning system (TPS) from Varian Medical Systems, Inc. to develop a novel treatment planning environment for synchrotron microbeam radiotherapy (MRT). This research license allows for customised dose calculation algorithms to be integrated with the clinical work-flows in Eclipse that are typical to modern radiotherapy. In this way, all the functionality of the Eclipse TPS familiar to many radiation oncology professionals is retained for application to MRT. Our TPS is designed for the dynamic MRT modality that has been developed for the imaging and medical beamline (IMBL) at the Australian synchrotron. The TPS uses a very simple algorithm for primary dose calculation, and we estimate the peak to valley dose ratio (PVDR) and hence the valley dose from data derived from a separate Monte Carlo simulation. At this stage the algorithm is a fast approximation with only simple radiological path length corrections to account for tissue inhomogeneities. However, the algorithm can highlight to oncology clinicians the strengths and limitations of synchrotron MRT, and furthermore, serves as a proof of concept and a start-point for implementing more advanced dose calculation algorithms. For the treatment itself, the incident synchrotron broad beam is collimated to a 30 mm wide by 1 mm high field which illuminates the MRT collimator, which in turn produces 50 μm wide vertical microbeams separated at 400 μm centre-to-centre. The sample and a mask is then dynamically swept through this array of microbeams, producing a dose of radiation in the sample that is conformal to a patient specific mask aperture. All properties of this irradiation methodology can be configured within the TPS and used for the design of MRT treatments. We present implementation details of our TPS for MRT and describe the hyperbolic relationship between PVDR and depth, and use it for calculating the water equivalent PVDR at different radiological depths.

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