Mini-GRID therapy delivers optimised spatially fractionated radiation therapy using a flattening free filter accelerator.

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.