Radiobiological effects and proton RBE determined by wildtype zebrafish embryos

Szabó, Éva; Brand, Michael; Hans, Stefan; Hidéghety, Katalin; Karsch, L.; Leßmann, Elisabeth; Pawelke, Jörg; Schürer, Michael; Beyreuther, Elke

doi:10.1371/journal.pone.0206879

Cited by 25 publications

(34 citation statements)

References 32 publications

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“…We therefore conclude that the effects of EP on survival are more similar to X-ray photons, at least as long as the MEFs have an intact DNA repair machinery (NHEJ, HRR). These observations corroborate findings obtained by others describing higher RBE values in a zebrafish model at mid SOBP compared to EP proton irradiation [71].…”

Section: Discussionsupporting

confidence: 92%

Proton Irradiation Increases the Necessity for Homologous Recombination Repair Along with the Indispensability of Non-Homologous End Joining

Szymonowicz

Krysztofiak

Linden

et al. 2020

Cells

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Technical improvements in clinical radiotherapy for maximizing cytotoxicity to the tumor while limiting negative impact on co-irradiated healthy tissues include the increasing use of particle therapy (e.g., proton therapy) worldwide. Yet potential differences in the biology of DNA damage induction and repair between irradiation with X-ray photons and protons remain elusive. We compared the differences in DNA double strand break (DSB) repair and survival of cells compromised in non-homologous end joining (NHEJ), homologous recombination repair (HRR) or both, after irradiation with an equal dose of X-ray photons, entrance plateau (EP) protons, and mid spread-out Bragg peak (SOBP) protons. We used super-resolution microscopy to investigate potential differences in spatial distribution of DNA damage foci upon irradiation. While DNA damage foci were equally distributed throughout the nucleus after X-ray photon irradiation, we observed more clustered DNA damage foci upon proton irradiation. Furthermore, deficiency in essential NHEJ proteins delayed DNA repair kinetics and sensitized cells to both, X-ray photon and proton irradiation, whereas deficiency in HRR proteins sensitized cells only to proton irradiation. We assume that NHEJ is indispensable for processing DNA DSB independent of the irradiation source, whereas the importance of HRR rises with increasing energy of applied irradiation.

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Section: Discussionsupporting

confidence: 92%

Proton Irradiation Increases the Necessity for Homologous Recombination Repair Along with the Indispensability of Non-Homologous End Joining

Szymonowicz

Krysztofiak

Linden

et al. 2020

Cells

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“…A meta-analysis of existing in vivo data from 2002 found no significant variation in the RBE and ratified the use of a constant RBE of 1.1 (Paganetti et al 2002). However, more recent experiment work on animal models, irradiated with multiple LETd values, have indeed indicated that there is a correlation between increased LET and RBE (Sørensen et al 2017, Saager et al 2018, Szabó et al 2018.…”

Section: The Effect Of Variable Rbementioning

confidence: 96%

Exploration and application of phenomenological RBE models for proton therapy

et al. 2018

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The relative biological effectiveness (RBE) of protons varies with multiple physical and biological factors. Phenomenological RBE models have been developed to include such factors in the estimation of a variable RBE, in contrast to the clinically applied constant RBE of 1.1. In this study, eleven published phenomenological RBE models and two plan-based models were explored and applied to simulated patient cases. All models were analysed with respect to the distribution and range of linear energy transfer (LET) and reference radiation fractionation sensitivity ((α/β) ) of their respective experimental databases. Proton therapy plans for a spread-out Bragg peak in water and three patient cases (prostate adenocarcinoma, pituitary adenoma and thoracic sarcoma) were optimised using an RBE of 1.1 in the Eclipse treatment planning system prior to recalculation and modelling in the FLUKA Monte Carlo code. Model estimated dose-volume parameters for the planning target volumes (PTVs) and organs at risk (OAR) were compared. The experimental in vitro databases for the various models differed greatly in the range of (α/β) values and dose-averaged LET (LET). There were significant variations between the model estimations, which arose from fundamental differences in the database definitions and model assumptions. The greatest variations appeared in organs with low (α/β) and high LET, e.g. biological doses given to late responding OARs located distal to the target in the treatment field. In general, the variation in maximum dose (D) was larger than the variation in mean dose and other dose metrics, with D of the left optic nerve ((α/β) = 2.1 Gy) in the pituitary adenoma case showing the greatest discrepancies between models: 28-52 Gy(RBE), while D for RBE was 30 Gy(RBE). For all patient cases, the estimated mean RBE to the PTV was in the range 1.09-1.29 ((α/β) = 1.5/3.1/10.6 Gy). There were considerable variations between the estimations of RBE and RBE-weighted doses from the different models. These variations were a consequence of fundamental differences in experimental databases, model assumptions and regression techniques. The results from the implementation of RBE models in dose planning studies should be evaluated in light of these deviations.

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“…In order to exclude potential LET (linear energy transfer) effects of low energy protons at the end of the proton path [7] irradiations were performed at the entrance plateau of the proton beam depth dose profile. Radiobiological effects of Flash versus conventional proton treatment were assessed by rating their influence on embryonic survival and the formation of morphological abnormalities [8].…”

Section: Introductionmentioning

confidence: 99%