Abstract
Simple SummaryThis study compares the capabilities of normal and tumour cells to divide after receiving spatially fractionated radiotherapy. For this treatment, a minority of cells (here ∼20%) receive very large, peak doses, whereas the remaining cells are spared and receive only a small valley dose. We show that tumour and normal cells respond differently to this treatment, and that spatially fractionated radiotherapy may have a greater effect on tumour than normal cells. Our work was conducted using laboratory equipment, rather than specialized synchrotron facilities implying that the observed response is present at conventional dose rates and hence purely an effect of the spatial fractionation of the treatment.Microbeam radiotherapy (MRT) is a preclinical method of delivering spatially-fractionated radiotherapy aiming to improve the therapeutic window between normal tissue complication and tumour control. Previously, MRT was limited to ultra-high dose rate synchrotron facilities. The aim of this study was to investigate in vitro effects of MRT on tumour and normal cells at conventional dose rates produced by a bench-top X-ray source. Two normal and two tumour cell lines were exposed to homogeneous broad beam (BB) radiation, MRT, or were separately irradiated with peak or valley doses before being mixed. Clonogenic survival was assessed and compared to BB-estimated surviving fractions calculated by the linear-quadratic (LQ)-model. All cell lines showed similar BB sensitivity. BB LQ-model predictions exceeded the survival of cell lines following MRT or mixed beam irradiation. This effect was stronger in tumour compared to normal cell lines. Dose mixing experiments could reproduce MRT survival. We observed a differential response of tumour and normal cells to spatially fractionated irradiations in vitro, indicating increased tumour cell sensitivity. Importantly, this was observed at dose rates precluding the presence of FLASH effects. The LQ-model did not predict cell survival when the cell population received split irradiation doses, indicating that factors other than local dose influenced survival after irradiation.
Highlights
Introduction distributed under the terms andAny cancer treatment aims to eradicate the tumour target, whilst inflicting minimal toxicity in healthy tissues
In order to compare the effectiveness of broad beam (BB) irradiation relative to microbeam radiation therapy (MRT), we first established the sensitivity of the cell lines to standard BB radiation (Figure 2, Table 1)
Having established that the cell lines under study displayed comparable sensitivity to BB irradiation, we evaluated MRT irradiation sensitivity, and predicted survival based upon the LQ-model with BB parameters (Equation (2))
Summary
Introduction distributed under the terms andAny cancer treatment aims to eradicate the tumour target, whilst inflicting minimal toxicity in healthy tissues. In radiation therapy (RT), this aim is conventionally achieved by geometrically confining the high dose field to the tumour, e.g., by intensity-modulated. RT, and thereby limiting side effects to organs at risk (OAR). Fractionated RT, such as microbeam radiation therapy (MRT) [1], has previously been suggested as an alternative strategy to maximise the therapeutic window between tumour control and normal tissue complication probability. MRT uses arrays of planar, high-dose beams of tens of μm width, which are separated by a few hundred micrometres. This spatial fractionation results in small regions of tissue receiving large (generally 300–800 Gy) peak doses being ablated, whereas spared areas receive a several-fold lower (valley) dose
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