Abstract
Proton minibeam radiation therapy (pMBRT) is a novel strategy for minimizing normal tissue damage resulting from radiotherapy treatments. This strategy partners the inherent advantages of protons for radiotherapy with the gain in normal tissue preservation observed upon irradiation with narrow, spatially fractionated beams. In this study, whole brains (excluding the olfactory bulb) of Fischer 344 rats (n = 16) were irradiated at the Orsay Proton Therapy Center. Half of the animals received standard proton irradiation, while the other half were irradiated with pMBRT at the same average dose (25 Gy in one fraction). The animals were followed-up for 6 months. A magnetic resonance imaging (MRI) study using a 7-T small-animal MRI scanner was performed along with a histological analysis. Rats treated with conventional proton irradiation exhibited severe moist desquamation, permanent epilation and substantial brain damage. In contrast, rats in the pMBRT group exhibited no skin damage, reversible epilation and significantly reduced brain damage; some brain damage was observed in only one out of the eight irradiated rats. These results demonstrate that pMBRT leads to an increase in normal tissue resistance. This net gain in normal tissue sparing can lead to the efficient treatment of very radio-resistant tumours, which are currently mostly treated palliatively.
Highlights
Proton minibeam radiation therapy is a novel radiotherapy (RT) strategy recently proposed[1] in order to lower the main barrier of RT treatments: the tolerance of normal tissues
Recent studies have demonstrated distinct biological properties of protons[12], which are not observed or are less frequently observed with photons, such as a complex DNA damage-inducing capacity and an ability to modulate inflammation[12]. These observations support an increase in the therapeutic index of Proton minibeam radiation therapy (pMBRT) over that of X-ray minibeam radiation therapy (MBRT)
6 out of 8 rats presented severe clinical symptoms, including apathy and reduced appetite, and 3 rats had to be sacrificed preliminarily due to a weight loss > 20% of their initial weight
Summary
Proton minibeam radiation therapy (pMBRT) is a novel radiotherapy (RT) strategy recently proposed[1] in order to lower the main barrier of RT treatments: the tolerance of normal tissues. Recent studies have demonstrated distinct biological properties of protons[12], which are not observed or are less frequently observed with photons, such as a complex DNA damage-inducing capacity and an ability to modulate inflammation[12] These observations support an increase in the therapeutic index of pMBRT over that of X-ray MBRT. The first biological indication of normal tissue (skin) sparing upon the combination of spatial dose fractionation with protons was provided by a recent experiment wherein mice ears were irradiated with 0.18 × 0.18-mm[2] grid patterns at a research facility[16]. Neither the beam energy (20 MeV) nor the grid size are clinically relevant[17], this work provided an initial indication of the potential gain in normal tissue resistance that can be achieved using these approaches
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