Background: Radioresistant tumours remain a challenge for conventional radiation therapy (RT), and often, only palliative treatment can be offered. Recently developed techniques, such as spatially fractionated radiation therapy (SFRT) could potentially improve treatment. However, current clinical SFRT implementations do not allow the full potential to be exploited. We further optimize SFRT, developing mini-GRID, which uses a flattening free filter accelerator.
Methods: The increase in normal tissue tolerances provided by mini-GRID compared to conventional RT and GRID therapy was validated in a rat model of brain irradiation in a longitudinal imaging study, behavioural tests and by histopathological evaluation.
Results: The implementation optimizes mini-GRID therapy, with beam widths around 2 mm2. The peak-to-valley dose ratios and peak dose rates are around 4 and 7 Gy/min, respectively. Mini-GRID RT allows the use of high peak doses: 42 Gy in one fraction, a factor more than twice higher than the peak doses generally employed in conventional GRID therapy (20 Gy peak dose). This enables the use of more aggressive and potentially curative treatments. Infrared microspectroscopy analysis suggests different early biochemical changes in both modalities, with conventional RT leading to stronger modifications in the secondary protein structure, and higher oxidative damage than mini-GRID RT.
Conclusions: The possibility to treat both large and small tumours, and to perform safe and potentially curative dose escalations in previously untreatable cases, makes mini-GRID a promising approach to expand the clinical use of SFRT.
Conventional radiation therapy is used to shrink tumours, however, in some cases, tumours become resistant to radiation, resulting in limited treatment options. To overcome this, we have developed a radiation therapy technique, called mini-GRID therapy that can target these hard-to-treat tumours. Mini-GRID therapy does this by distributing the dose of radiation across the tissue instead of localized to one spot, allowing for a higher dose to be applied. Here, we demonstrate the feasibility and reduction of side effects on normal tissues using rat brain tissue following mini-GRID therapy. Our results show that the mini-GRID has the potential to improve radiation therapy in tumours that are resistant to radiation or require a higher dose to reduce tumour size without affecting normal tissue. This could provide a treatment strategy for currently untreatable brain tumours.
© 2025. The Author(s).