Toward personalized synchrotron microbeam radiation therapy

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 groundbreaking 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.

Iodine nanoparticle radiotherapy of human breast cancer growing in the brains of athymic mice

“…6c). Even smaller spatial beam segmentation (25-50 μm) with better tissue sparing is possible with the highly collimated X-rays produced by synchrotrons (Synchrotron Microbeam RT) [51][52][53][54] since synchrotrons operate at high intensity enabling very short exposures which avoid merging of the segments that would otherwise occur due to tissue blood pulsations. For both mini-and microbeams it was found that blood vessels in the intervening unirradiated segments could repair the irradiated adjacent segments with no consequential residual damage, thus greatly reducing the entrance dose damage 55 .…”

Incorporating Clinical Imaging into the Delivery of Microbeam Radiation Therapy

“…The validation of the image guidance system was applied to an in vivo experiment described in Engels et al 2020 [30]. As a means of validation of the targeting system, the position of the microbeam array relative to the centre of the tumour was measured using the brain histology of a rat in this study, 14 days after MRT.…”

“…In this study, we assess and evaluate the imaging, tumour identification, and patient alignment for small animal irradiation on IMBL. We present an end-to-end demonstration of the image-guided microbeam radiation therapy protocol used for Australia's first long term pre-clinical MRT treatment of rats bearing 9L gliosarcoma tumours [30]. The protocol, as proposed in this work, utilises a clinical CT scanner for the identification of the tumour volume and skeletal landmarks used for patient specific alignment.…”

Perspectives for microbeam irradiation at the SYRMEP beamline

“…Therapeutic efficacy has been demonstrated in several small-animal models of malignant brain tumours (Laissue et al, 1998;Miura et al, 2006;Bouchet et al, 2016;Schü ltke et al, 2018;Engels et al, 2020). The results of other studies have shown evidence of a remarkably high normal-tissue tolerance (Laissue et al, 2007;Schü ltke et al, 2008;Bouchet et al, 2010).…”