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

Baiocco, G.; Bartzsch, Stefan; Conte, V.; Friedrich, Thomas; Jakob, Burkhard; Tartas, Adrianna; Villagrasa, C.; Prise, Kevin M.

doi:10.1007/s00411-022-00989-z

Cited by 20 publications

(15 citation statements)

References 108 publications

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“…The MELODI Workshop 2020 on the “Spatial and temporal variation in dose delivery” brought together experts in clinical/epidemiological/dosimetric and biological/mechanistic aspects of research. It was organized in four sessions, addressing (1) dose-rate effects, (2) radiation quality, (3) internal exposure and (4) partial body exposure, each generating at least one thematic manuscript (Lowe et al 2022 ; Baiocco et al 2022 ; Boei et al 2022 ; Li et al 2022 ). Due to COVID19 outbreak, the workshop was successfully held on-line.…”

Section: Introductionmentioning

confidence: 99%

Out-of-field effects: lessons learned from partial body exposure

Pazzaglia

Eidemüller

Lumniczky³

et al. 2022

Radiat Environ Biophys

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Partial body exposure and inhomogeneous dose delivery are features of the majority of medical and occupational exposure situations. However, mounting evidence indicates that the effects of partial body exposure are not limited to the irradiated area but also have systemic effects that are propagated outside the irradiated field. It was the aim of the “Partial body exposure” session within the MELODI workshop 2020 to discuss recent developments and insights into this field by covering clinical, epidemiological, dosimetric as well as mechanistic aspects. Especially the impact of out-of-field effects on dysfunctions of immune cells, cardiovascular diseases and effects on the brain were debated. The presentations at the workshop acknowledged the relevance of out-of-field effects as components of the cellular and organismal radiation response. Furthermore, their importance for the understanding of radiation-induced pathologies, for the discovery of early disease biomarkers and for the identification of high-risk organs after inhomogeneous exposure was emphasized. With the rapid advancement of clinical treatment modalities, including new dose rates and distributions a better understanding of individual health risk is urgently needed. To achieve this, a deeper mechanistic understanding of out-of-field effects in close connection to improved modelling was suggested as priorities for future research. This will support the amelioration of risk models and the personalization of risk assessments for cancer and non-cancer effects after partial body irradiation.

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Section: Introductionmentioning

confidence: 99%

Out-of-field effects: lessons learned from partial body exposure

Pazzaglia

Eidemüller

Lumniczky³

et al. 2022

Radiat Environ Biophys

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“…Notably, (Conte et al 2018, Selva et al 2020, nanodosimetry offers a direct pathway to understanding the biological consequences of radiation exposure. Furthermore, it has become evident that both microdosimetric and nanodosimetric scales play a significant role in assessing radiation-induced biological damage (Friedrich et al 2018, Baiocco et al 2022. However, it is crucial to highlight that accurately simulating nanoscale phenomena necessitates the implementation of a physics list based on track structure, which, for the sake of clarity, is not the focus of this paper.…”

Section: Introductionmentioning

confidence: 99%

Integrating microdosimetric in vitro RBE models for particle therapy into TOPAS MC using the MicrOdosimetry-based modeliNg for RBE ASsessment (MONAS) tool

Cartechini,

Missiaggia,

Scifoni

et al. 2024

Phys. Med. Biol.

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Objective: In this paper, we present MONAS (MicrOdosimetry-based modelliNg for relative biological effectiveness (RBE) ASsessment) toolkit. MONAS is a TOPAS Monte Carlo extension, that combines simulations of microdosimetric distributions with radiobiological microdosimetry-based models for predicting cell survival curves and dose-dependent RBE.Approach: MONAS expands TOPAS microdosimetric extension, by including novel specific energy scorers to calculate the single- and multi-event specific energy microdosimetric distributions at different micrometer scales. These spectra are used as physical input to three different formulations of the Microdosimetric Kinetic Model (MKM), and to the Generalized Stochastic Microdosimetric Model (GSM2), to predict dose-dependent cell survival fraction and RBE. MONAS predictions are then validated against experimental microdosimetric spectra and in vitro survival fraction data. To show the MONAS features, we present two different applications of the code: i) the depth-RBE curve calculation from a passively scattered proton SOBP by using experimentally validated spectra as physical input, and ii) the calculation of the 3D RBE distribution on a real head and neck patient geometry treated with protons.Main results: MONAS can estimate dose-dependent RBE and cell survival curves from experimentally validated microdosimetric spectra with four clinically relevant radiobiological models. From the radiobiological characterization of a proton SOBP field, we observe the well-known trend of increasing RBE values at the distal edge of the radiation field. The 3D RBE map calculated confirmed the trend observed in the analysis of the SOBP, with the highest RBE values found in the distal edge of the target.Significance: MONAS extension offers a comprehensive microdosimetry-based framework for assessing the biological effects of particle radiation in both research and clinical environments, pushing closer the experimental physics-based description to the biological damage assessment, contributing to bridging the gap between a microdosimetric description of the radiation field and its application in proton therapy treatment with variable RBE.

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“…The aim of this review is to provide an overview on the state of the art in epidemiology, clinical observations, cell biology, dosimetry, and modelling related to radon exposure along with priorities for future research. As the effects of spatial heterogeneity in energy deposition (Baiocco et al 2022), partial body exposures (Pazzaglia et al 2022), and dose rate (Lowe et al 2022) are covered in other papers of this theme issue, particular attention is paid here on the effects of spatial variation in dose delivery in the lungs upon radon exposure, a factor not considered in radiation protection (Madas 2016a).…”

Section: Introductionmentioning

confidence: 99%

Effects of spatial variation in dose delivery: what can we learn from radon-related lung cancer studies?

Madas

Boei

Fenske

et al. 2022

Radiat Environ Biophys

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Exposure to radon progeny results in heterogeneous dose distributions in many different spatial scales. The aim of this review is to provide an overview on the state of the art in epidemiology, clinical observations, cell biology, dosimetry, and modelling related to radon exposure and its association with lung cancer, along with priorities for future research. Particular attention is paid on the effects of spatial variation in dose delivery within the organs, a factor not considered in radiation protection. It is concluded that a multidisciplinary approach is required to improve risk assessment and mechanistic understanding of carcinogenesis related to radon exposure. To achieve these goals, important steps would be to clarify whether radon can cause other diseases than lung cancer, and to investigate radon-related health risks in children or persons at young ages. Also, a better understanding of the combined effects of radon and smoking is needed, which can be achieved by integrating epidemiological, clinical, pathological, and molecular oncology data to obtain a radon-associated signature. While in vitro models derived from primary human bronchial epithelial cells can help to identify new and corroborate existing biomarkers, they also allow to study the effects of heterogeneous dose distributions including the effects of locally high doses. These novel approaches can provide valuable input and validation data for mathematical models for risk assessment. These models can be applied to quantitatively translate the knowledge obtained from radon exposure to other exposures resulting in heterogeneous dose distributions within an organ to support radiation protection in general.

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

Cited by 20 publications

References 108 publications

Out-of-field effects: lessons learned from partial body exposure

Out-of-field effects: lessons learned from partial body exposure

Integrating microdosimetric in vitro RBE models for particle therapy into TOPAS MC using the MicrOdosimetry-based modeliNg for RBE ASsessment (MONAS) tool

Effects of spatial variation in dose delivery: what can we learn from radon-related lung cancer studies?

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