The relative biological effectiveness of carbon ion irradiations of the rat spinal cord increases linearly with LET up to 99 keV/μm

Saager, Maria; Glowa, Christin; Peschke, Peter; Brons, Stephan; Grün, Rebecca; Scholz, M.; Huber, Peter E.; Debus, Jürgen; Karger, Christian P.

doi:10.1080/0284186x.2016.1250947

Cited by 32 publications

(45 citation statements)

References 22 publications

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“…However, in brief, the impact of the corresponding model improvements becomes visible essentially in two aspects. The first is related to the steeper gradient in particle LET with increasing LET in the LEM IV as compared to LEM I; comparisons with experimental data regarding the tolerance of the nervous system, which are of particular interest for clinical applications, provide some evidence that this steeper gradient is more realistic than the gradient predicted in LEM I . The second aspect is related to the better simultaneous agreement of model predictions of particle RBE in vitro over a broader range of therapeutically relevant ion species and energies (i.e., protons up to carbon ions) without the need for parameter optimization for individual ion species .…”

Section: Rbe Models and Mechanisms Of Actionmentioning

confidence: 99%

“…regarding the tolerance of the nervous system, which are of particular interest for clinical applications, provide some evidence that this steeper gradient is more realistic than the gradient predicted in LEM I. 77,78 The second aspect is related to the better simultaneous agreement of model predictions of particle RBE in vitro over a broader range of therapeutically relevant ion species and energies (i.e., protons up to carbon ions) without the need for parameter optimization for individual ion species. 45,79 Applications of LEM I in the clinical environment are most accurate for carbon ions.…”

Section: A Lem IVmentioning

confidence: 99%

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A comparison of mechanism‐inspired models for particle relative biological effectiveness (RBE)

et al. 2018

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Background and Significance The application of heavy ion beams in cancer therapy must account for the increasing relative biological effectiveness (RBE) with increasing penetration depth when determining dose prescriptions and organ at risk (OAR) constraints in treatment planning. Because RBE depends in a complex manner on factors such as the ion type, energy, cell and tissue radiosensitivity, physical dose, biological endpoint, and position within and outside treatment fields, biophysical models reflecting these dependencies are required for the personalization and optimization of treatment plans. Aim To review and compare three mechanism‐inspired models which predict the complexities of particle RBE for various ion types, energies, linear energy transfer (LET) values and tissue radiation sensitivities. Methods The review of models and mechanisms focuses on the Local Effect Model (LEM), the Microdosimetric‐Kinetic (MK) model, and the Repair‐Misrepair‐Fixation (RMF) model in combination with the Monte Carlo Damage Simulation (MCDS). These models relate the induction of potentially lethal double strand breaks (DSBs) to the subsequent interactions and biological processing of DSB into more lethal forms of damage. A key element to explain the increased biological effectiveness of high LET ions compared to MV x rays is the characterization of the number and local complexity (clustering) of the initial DSB produced within a cell. For high LET ions, the spatial density of DSB induction along an ion's trajectory is much greater than along the path of a low LET electron, such as the secondary electrons produced by the megavoltage (MV) x rays used in conventional radiation therapy. The main aspects of the three models are introduced and the conceptual similarities and differences are critiqued and highlighted. Model predictions are compared in terms of the RBE for DSB induction and for reproductive cell survival. Results and Conclusions Comparisons of the RBE for DSB induction and for cell survival are presented for proton (1H), helium (4He), and carbon (12C) ions for the therapeutically most relevant range of ion beam energies. The reviewed models embody mechanisms of action acting over the spatial scales underlying the biological processing of potentially lethal DSB into more lethal forms of damage. Differences among the number and types of input parameters, relevant biological targets, and the computational approaches among the LEM, MK and RMF models are summarized and critiqued. Potential experiments to test some of the seemingly contradictory aspects of the models are discussed.

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Section: Rbe Models and Mechanisms Of Actionmentioning

confidence: 99%

Section: A Lem IVmentioning

confidence: 99%

A comparison of mechanism‐inspired models for particle relative biological effectiveness (RBE)

et al. 2018

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“…While all ion types offer highly conformal irradiation of the tumor with excellent sparing of the surrounding normal tissue, the clinical rationale of CIRT especially includes the assumption that the RBE within the tumor is higher than in the surrounding normal tissue. Although the respective RBE distribution may be calculated by RBE models, it has to be emphasized that RBE models consider only the dependencies of some of the physical and biological parameters and even these predictions are associated with significant uncertainties . There are many biological factors, which may influence the RBE, but which are not included in the RBE models.…”

Section: Review Of Radiobiological Issues and Clinical Trialsmentioning

confidence: 99%

“…Although the respective RBE distribution may be calculated by RBE models, it has to be emphasized that RBE models consider only the dependencies of some of the physical and biological parameters and even these predictions are associated with significant uncertainties. 27,[32][33][34]45 There are many biological factors, which may influence the RBE, but which are not included in the RBE models. For example, it has been shown that differences in the progression status of different tumor sublines as well as the biological heterogeneity within the same subline have less impact on the radiation response for high-LET radiation as compared with photons.…”

Section: C Clinical Trialsmentioning

confidence: 99%

Radiobiological issues in prospective carbon ion therapy trials

Fossati

Matsufuji²,

Kamada³

et al. 2018

Medical Physics

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Carbon ion radiotherapy (CIRT) is developing toward a versatile tool in radiotherapy; however, the increased relative biological effectiveness (RBE) of carbon ions in tumors and normal tissues with respect to photon irradiation has to be considered by mathematical models in treatment planning. As a consequence, dose prescription and definition of dose constraints are performed in terms of RBE weighted rather than absorbed dose. The RBE is a complex quantity, which depends on physical variables, such as dose and beam quality as well as on normal tissue‐ or tumor‐specific factors. At present, three RBE models are employed in CIRT: (a) the mixed‐beam model, (b) the Microdosimetric Kinetic Model (MKM), and (c) the local effect model. While the LEM is used in Europe, the other two models are employed in Japan, and unfortunately, the concepts of how the nominal RBE‐weighted dose is determined and prescribed differ significantly between the European and Japanese centers complicating the comparison, transfer, and reproduction of clinical results. This has severe impact on the way treatments should be prescribed, recorded, and reported. This contribution reviews the concept of the clinical application of the different RBE models and the ongoing clinical CIRT trials in Japan and Europe. Limitations of the RBE models and the resulting radiobiological issues in clinical CIRT trials are discussed in the context of current clinical evidence and future challenges.

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“…[6][7][8] Generic RBE of 1.1 has been implemented for proton treatment planning, 5,6) and RBE prediction models have been applied to for heavy ion treatment planning since the RBE changes rapidly with LET of heavy ion compared to proton. 9,10) Hence, particle beam therapy centers need to evaluate biological dose with RBE measurement via in vitro or in vivo experiments before the clinical application of the particle beam.…”

Section: Introductionmentioning

confidence: 99%

Development of Program for Relative Biological Effectiveness (RBE) Analysis of Particle Beam Therapy

et al. 2017

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The relative biological effectiveness of carbon ion irradiations of the rat spinal cord increases linearly with LET up to 99 keV/μm

Abstract: (2016) The relative biological effectiveness of carbon ion irradiations of the rat spinal cord increases linearly with LET up to 99 keV/µm,

Cited by 32 publications

References 22 publications

A comparison of mechanism‐inspired models for particle relative biological effectiveness (RBE)

A comparison of mechanism‐inspired models for particle relative biological effectiveness (RBE)

Radiobiological issues in prospective carbon ion therapy trials

Development of Program for Relative Biological Effectiveness (RBE) Analysis of Particle Beam Therapy

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