Calculation of relative biological effectiveness for proton beams using biological weighting functions

Paganetti, Harald; Olko, P.; Kobus, H.; Becker, Regina; Schmitz, Thomas; Waligórski, M.P.R.; Filges, D.; Müller‐Gärtner, Hans‐Wilhelm

doi:10.1016/s0360-3016(96)00540-8

Cited by 73 publications

(63 citation statements)

References 28 publications

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“…LET has been demonstrated to increase steeply at the distal end of the SOBP [11, 20, 24]. Consistent with the reports of several previous investigators in regard to the existence of a significant relationship between the RBE and LET [11, 12, 25], the current study also showed a trend towards a positive correlation between the RBE and LET for both cell lines, despite their different sensitivities to the proton beam.…”

Section: Discussionsupporting

confidence: 91%

Difference in the relative biological effectiveness and DNA damage repair processes in response to proton beam therapy according to the positions of the spread out Bragg peak

et al. 2017

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BackgroundCellular responses to proton beam irradiation are not yet clearly understood, especially differences in the relative biological effectiveness (RBE) of high-energy proton beams depending on the position on the Spread-Out Bragg Peak (SOBP). Towards this end, we investigated the differences in the biological effect of a high-energy proton beam on the target cells placed at different positions on the SOBP, using two human esophageal cancer cell lines with differing radiosensitivities.MethodsTwo human esophageal cancer cell lines (OE21, KYSE450) with different radiosensitivities were irradiated with a 235-MeV proton beam at 4 different positions on the SOBP (position #1: At entry; position #2: At the proximal end of the SOBP; position #3: Center of the SOBP; position #4: At the distal end of the SOBP), and the cell survivals were assessed by the clonogenic assay. The RBE10 for each position of the target cell lines on the SOBP was determined based on the results of the cell survival assay conducted after photon beam irradiation. In addition, the number of DNA double-strand breaks was estimated by quantitating the number of phospho-histone H2AX (γH2AX) foci formed in the nuclei by immunofluorescence analysis.ResultsIn regard to differences in the RBE of a proton beam according to the position on the SOBP, the RBE value tended to increase as the position on the SOBP moved distally. Comparison of the residual number of γH2AX foci at the end 24 h after the irradiation revealed, for both cell lines, a higher number of foci in the cells irradiated at the distal end of the SOPB than in those irradiated at the proximal end or center of the SOBP.ConclusionsThe results of this study demonstrate that the RBE of a high-energy proton beam and the cellular responses, including the DNA damage repair processes, to high-energy proton beam irradiation, differ according to the position on the SOBP, irrespective of the radiosensitivity levels of the cell lines.Electronic supplementary materialThe online version of this article (doi:10.1186/s13014-017-0849-1) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 91%

Difference in the relative biological effectiveness and DNA damage repair processes in response to proton beam therapy according to the positions of the spread out Bragg peak

et al. 2017

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“…Measurements had revealed that RBEm varies from 1.1 to 1.4 in the SOBP and reaches values as high as 2.7 at the distal edge. Those data were in good agreement with the calculations of Paganetti et al (1997) and with radiobiological measurements (Courdi et al, 1994;Bettega et al, 2000). Moreover, measurements performed outside the collimator edge had shown that RBEm increased by 10% (De Nardo et al, 2004a) at 2.5 mm from the collimator edge, which was higher than those calculated by Van Luijk et al (2001).…”

Section: Introductionsupporting

confidence: 88%

Microdosimetric characterisation of a therapeutic proton beam used for conjunctival melanoma treatments

Nardo

Colautti

Hérault³

et al. 2010

Radiation Measurements

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“…Although in clinical application of proton beams for radiotherapy the generic RBE of 1.1 continues to be widely used, as recommended by ICRU Report 78, there has been a growing interest among those involved with biophysical modeling, in devising ways to accommodate variation in RBE values in treatment planning (51)(52)(53)(54)(55)(56)(57)(58)(59)(60)(61)(62). Some of those models rely on biological measurements, both in vitro and in vivo, to characterize some of the model parameters.…”

Section: Biophysical Modelingmentioning

confidence: 99%

Radiobiological Intercomparison of the 160 MeV and 230 MeV Proton Therapy Beams at the Harvard Cyclotron Laboratory and at Massachusetts General Hospital

Wouters

Skarsgard²,

Gerweck

et al. 2015

Radiation Research

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The purpose of this study was to determine the relative biological effectiveness (RBE) along the axis of two range-modulated proton beams (160 and 230 MeV). Both the depth and the dose dependence of RBE were investigated. Chinese hamster V79-WNRE cells, suspended in medium containing gelatin and cooled to 2 °C, were used to obtain complete survival curves at multiple positions throughout the entrance and 10 cm spread-out Bragg peak (SOBP). Simultaneous measurements of the survival response to (60)Co gamma rays served as the reference data for the proton RBE determinations. For both beams the RBE increased significantly with depth in the 10 cm SOBP, particularly in the distal half of the SOBP, then rose even more sharply at the distal edge, the most distal position measured. At a 4 Gy dose of gamma radiation (S = 0.34) the average RBE values for the entrance, proximal half, distal half and distal edge were 1.07 ± 0.01, 1.10 ± 0.01, 1.17 ± 0.01 and 1.21 ± 0.01, respectively, and essentially the same for both beams. At a 2 Gy dose of gamma radiation (S = 0.71) the average RBE values rose to 1.13 ± 0.03, 1.15 ± 0.02, 1.26 ± 0.02 and 1.30 ± 0.02, respectively, for the same four regions of the SOBP. The difference between the 4 Gy and 2 Gy RBE values reflects the dose dependence of RBE as measured in these V79-WNRE cells, which have a low α/β value, as do other widely used cell lines that also show dose-dependent RBE values. Late-responding tissues are also characterized by low α/β values, so it is possible that these cell lines may be predictive for the response of such tissues (e.g., spinal cord, optic nerve, kidney, liver, lung). However, in the very small number of studies of late-responding tissues performed to date there appears to be no evidence of an increased RBE for protons at low doses. Similarly, RBE measurements using early responding in vivo systems (mostly mouse jejunum, an early-responding tissue which has a large α/β ∼ 10 Gy) have generally shown little or no detectable dose dependence. It is useful to compare the RBE values reported here to the commonly used generic clinical RBE of 1.1, which assumes no dependence on depth or on dose. Our proximal RBEs obviously avoid the depth-related increase in RBE and for doses of 4 Gy or more, the low-dose increase in RBE is also minimized, as shown in this article. Thus the proximal RBE at a 4 Gy dose of 1.10 ± 0.01, quoted above, represents an interesting point of congruence with the clinical RBE for conditions where it could reasonably be expected in the measurements reported here. The depth dependence of RBE reported here is consistent with the majority of measurements, both in vitro and in vivo, by other investigators. The dose dependence of RBE, on the other hand, is tissue specific but has not yet been demonstrated for protons by RBE values in late-responding normal tissue systems. This indicates a need for additional RBE determination as function of dose, especially in late-responding tissues.

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Calculation of relative biological effectiveness for proton beams using biological weighting functions

Cited by 73 publications

References 28 publications

Difference in the relative biological effectiveness and DNA damage repair processes in response to proton beam therapy according to the positions of the spread out Bragg peak

Difference in the relative biological effectiveness and DNA damage repair processes in response to proton beam therapy according to the positions of the spread out Bragg peak

Microdosimetric characterisation of a therapeutic proton beam used for conjunctival melanoma treatments

Radiobiological Intercomparison of the 160 MeV and 230 MeV Proton Therapy Beams at the Harvard Cyclotron Laboratory and at Massachusetts General Hospital

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