Quantification of Differential Response of Tumour and Normal Cells to Microbeam Radiation in the Absence of FLASH Effects

Steel, Harriet; Brüningk, Sarah C.; Box, Carol; Oelfke, Uwe; Bartzsch, Stefan

doi:10.3390/cancers13133238

Cited by 11 publications

(11 citation statements)

References 48 publications

(61 reference statements)

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“…As an example, line-focus X-ray tubes are being considered as microbeam source and Monte Carlo simulations have demonstrated they have a great potential as a radiation source for clinical application [ 82 ], of MRT. With this respect it is also important to mention recent studies in which in-vitro MRT treatments performed with laboratory sources at conventional dose rates enhanced an increased tumor cell sensitivity [ 83 , 84 ].…”

Section: Discussionmentioning

confidence: 99%

A Multi-Scale and Multi-Technique Approach for the Characterization of the Effects of Spatially Fractionated X-ray Radiation Therapies in a Preclinical Model

Romano

Bravin

Mittone

et al. 2021

Cancers

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The purpose of this study is to use a multi-technique approach to detect the effects of spatially fractionated X-ray Microbeam (MRT) and Minibeam Radiation Therapy (MB) and to compare them to seamless Broad Beam (BB) irradiation. Healthy- and Glioblastoma (GBM)-bearing male Fischer rats were irradiated in-vivo on the right brain hemisphere with MRT, MB and BB delivering three different doses for each irradiation geometry. Brains were analyzed post mortem by multi-scale X-ray Phase Contrast Imaging–Computed Tomography (XPCI-CT), histology, immunohistochemistry, X-ray Fluorescence (XRF), Small- and Wide-Angle X-ray Scattering (SAXS/WAXS). XPCI-CT discriminates with high sensitivity the effects of MRT, MB and BB irradiations on both healthy and GBM-bearing brains producing a first-time 3D visualization and morphological analysis of the radio-induced lesions, MRT and MB induced tissue ablations, the presence of hyperdense deposits within specific areas of the brain and tumor evolution or regression with respect to the evaluation made few days post-irradiation with an in-vivo magnetic resonance imaging session. Histology, immunohistochemistry, SAXS/WAXS and XRF allowed identification and classification of these deposits as hydroxyapatite crystals with the coexistence of Ca, P and Fe mineralization, and the multi-technique approach enabled the realization, for the first time, of the map of the differential radiosensitivity of the different brain areas treated with MRT and MB. 3D XPCI-CT datasets enabled also the quantification of tumor volumes and Ca/Fe deposits and their full-organ visualization. The multi-scale and multi-technique approach enabled a detailed visualization and classification in 3D of the radio-induced effects on brain tissues bringing new essential information towards the clinical implementation of the MRT and MB radiation therapy techniques.

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Section: Discussionmentioning

confidence: 99%

A Multi-Scale and Multi-Technique Approach for the Characterization of the Effects of Spatially Fractionated X-ray Radiation Therapies in a Preclinical Model

Romano

Bravin

Mittone

et al. 2021

Cancers

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“…Spatially fractionated radiation therapy was first used to exploit the advantage of skin-sparing effects in patients while enabling a high dose rate to refractory tumours in palliative treatments. Potential use of GRID, or other applications of SFRT, such as MRT, beyond the original palliative applications, and even multi-technique approaches [ 7 , 8 ] have been investigated due to findings of a greater therapeutic index resulting from both the increased normal tissue sparing and the greater tumour toxicity when compared to conventional temporally fractionated radiation therapy [ 9 , 10 , 11 , 12 ].…”

Section: Molecular and Radiobiological Mechanisms Of Spatially Fracti...mentioning

confidence: 99%

Radiobiological and Treatment-Related Aspects of Spatially Fractionated Radiotherapy

Moghaddasi

Reid²,

Bezak

et al. 2022

IJMS

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The continuously evolving field of radiotherapy aims to devise and implement techniques that allow for greater tumour control and better sparing of critical organs. Investigations into the complexity of tumour radiobiology confirmed the high heterogeneity of tumours as being responsible for the often poor treatment outcome. Hypoxic subvolumes, a subpopulation of cancer stem cells, as well as the inherent or acquired radioresistance define tumour aggressiveness and metastatic potential, which remain a therapeutic challenge. Non-conventional irradiation techniques, such as spatially fractionated radiotherapy, have been developed to tackle some of these challenges and to offer a high therapeutic index when treating radioresistant tumours. The goal of this article was to highlight the current knowledge on the molecular and radiobiological mechanisms behind spatially fractionated radiotherapy and to present the up-to-date preclinical and clinical evidence towards the therapeutic potential of this technique involving both photon and proton beams.

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“…At the cellular level, the tissue integrity and tumour control will likely depend on the number of surviving, clonogenic cells and potentially on the survival of resistant stem cells (Niwa et al 2015). While the high peak doses kill almost all cells, the level of the valley dose will determine cell survival and, indeed, many studies show the dependence of normal tissue effects on the valley dose and show that the valley dose is important for biological effects in vitro (Steel et al 2021) and in vivo (Serduc et al 2009, Smyth et al 2018. Nonetheless, processes originating from tissue parts within the radiation peaks are likely to cause the (Sabatasso et al 2021) differential effect and there are several hypothesized mechanisms involving the microenvironment of normal tissue and tumour.…”

Section: Spatially Fractionated Beams: Cell and Tissue Effects Toward...mentioning

confidence: 99%

A matter of space: how the spatial heterogeneity in energy deposition determines the biological outcome of radiation exposure

Baiocco

Bartzsch

Conte

et al. 2022

Radiat Environ Biophys

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The outcome of the exposure of living organisms to ionizing radiation is determined by the distribution of the associated energy deposition at different spatial scales. Radiation proceeds through ionizations and excitations of hit molecules with an ~ nm spacing. Approaches such as nanodosimetry/microdosimetry and Monte Carlo track-structure simulations have been successfully adopted to investigate radiation quality effects: they allow to explore correlations between the spatial clustering of such energy depositions at the scales of DNA or chromosome domains and their biological consequences at the cellular level. Physical features alone, however, are not enough to assess the entity and complexity of radiation-induced DNA damage: this latter is the result of an interplay between radiation track structure and the spatial architecture of chromatin, and further depends on the chromatin dynamic response, affecting the activation and efficiency of the repair machinery. The heterogeneity of radiation energy depositions at the single-cell level affects the trade-off between cell inactivation and induction of viable mutations and hence influences radiation-induced carcinogenesis. In radiation therapy, where the goal is cancer cell inactivation, the delivery of a homogenous dose to the tumour has been the traditional approach in clinical practice. However, evidence is accumulating that introducing heterogeneity with spatially fractionated beams (mini- and microbeam therapy) can lead to significant advantages, particularly in sparing normal tissues. Such findings cannot be explained in merely physical terms, and their interpretation requires considering the scales at play in the underlying biological mechanisms, suggesting a systemic response to radiation.

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Quantification of Differential Response of Tumour and Normal Cells to Microbeam Radiation in the Absence of FLASH Effects

Cited by 11 publications

References 48 publications

A Multi-Scale and Multi-Technique Approach for the Characterization of the Effects of Spatially Fractionated X-ray Radiation Therapies in a Preclinical Model

A Multi-Scale and Multi-Technique Approach for the Characterization of the Effects of Spatially Fractionated X-ray Radiation Therapies in a Preclinical Model

Radiobiological and Treatment-Related Aspects of Spatially Fractionated Radiotherapy

A matter of space: how the spatial heterogeneity in energy deposition determines the biological outcome of radiation exposure

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