Radiotherapy (Rt) is one of the most frequently used methods for cancer treatment. Despite remarkable advancements in Rt techniquesthe treatment of radioresistant tumours (i.e. high-grade gliomas) is not yet satisfactory. finding novel approaches less damaging for normal tissues is of utmost importance. this would make it possible to increase the dose applied to tumours, resulting in an improvement in the cure rate. Along this line, proton minibeam radiation therapy (pMBRt) is a novel strategy that allows the spatial modulation of the dose, leading to minimal damage to brain structures compared to a high dose (25 Gy in one fraction) of standard proton therapy (PT). the aim of the present study was to evaluate whether pMBRt also preserves important cerebral functions. comprehensive longitudinal behavioural studies were performed in irradiated (peak dose of 57 Gy in one fraction) and control rats to evaluate the impact of pMBRT on motor function (motor coordination, muscular tonus, and locomotor activity), emotional function (anxiety, fear, motivation, and impulsivity), and cognitive function (learning, memory, temporal processing, and decision making). The evaluations, which were conducted over a period of 10 months, showed no significant motor or emotional dysfunction in pMBRt-irradiated rats compared with control animals. concerning cognitive functions, similar performance was observed between the groups, although some slight learning delays might be present in some of the tests in the long term after irradiation. this study shows the minimal impact of pMBRt on the normal brain at the functional level. Radiotherapy (RT) is one of the main choices for cancer treatment 1. The remarkable achievements in dose conformation in the last decades 2 resulted in an improvement of the therapeutic index of RT treatments. However, the treatment of radioresistant tumours is not yet satisfactory. The reduced risk of normal tissue complications observed for spatially fractionated radiotherapy techniques 3-8 could be exploited to find an effective therapeutic strategy for these challenging cases. Along this line, a novel approach called proton minibeam radiation therapy (pMBRT) has been proposed 9. In contrast to standard proton therapy, irradiation in pMBRT is performed with narrow beams (diameter ≤ 1 mm) separated by gaps of 2 to 4 mm 9. This results in a lateral dose profile consisting of a series of high doses (peaks) and low doses (valleys).
(1) Background: Proton minibeam radiation therapy (pMBRT) is a new radiotherapy technique using spatially modulated narrow proton beams. pMBRT results in a significantly reduced local tissue toxicity while maintaining or even increasing the tumor control efficacy as compared to conventional radiotherapy in small animal experiments. In all the experiments performed up to date in tumor bearing animals, the dose was delivered in one single fraction. This is the first assessment on the impact of a temporal fractionation scheme on the response of glioma-bearing animals to pMBRT. (2) Methods: glioma-bearing rats were irradiated with pMBRT using a crossfire geometry. The response of the irradiated animals in one and two fractions was compared. An additional group of animals was also treated with conventional broad beam irradiations. (3) Results: pMBRT delivered in two fractions at the biological equivalent dose corresponding to one fraction resulted in the highest median survival time, with 80% long-term survivors free of tumors. No increase in local toxicity was noted in this group with respect to the other pMBRT irradiated groups. Conventional broad beam irradiations resulted in the most severe local toxicity. (4) Conclusion: Temporal fractionation increases the therapeutic index in pMBRT and could ease the path towards clinical trials.
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