Systematics of relative biological effectiveness measurements for proton radiation along the spread out Bragg peak: experimental validation of the local effect model

2017 ◽  
Vol 62 (3) ◽  
pp. 890-908 ◽  
Author(s):  
Rebecca Grün ◽  
Thomas Friedrich ◽  
Michael Krämer ◽  
Michael Scholz
Keyword(s):  
Experimental Validation ◽  
Bragg Peak ◽  
Relative Biological Effectiveness ◽  
Local Effect ◽  
Proton Radiation ◽  
Effect Model ◽  
Biological Effectiveness ◽  
Spread Out Bragg Peak

scholarly journals Fractionated carbon ion irradiations of the rat spinal cord: comparison of the relative biological effectiveness with predictions of the local effect model

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Maria Saager ◽  
Christin Glowa ◽  
Peter Peschke ◽  
Stephan Brons ◽  
Rebecca Grün ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Relative Biological Effectiveness ◽  
Local Effect ◽  
Published Data ◽  
Carbon Ions ◽  
Rat Spinal Cord ◽  
Model Calculations ◽  
Carbon Ion ◽  
Effect Model ◽  
Biological Effectiveness

Abstract Background To determine the relative biological effectiveness (RBE) and α/β-values after fractionated carbon ion irradiations of the rat spinal cord with varying linear energy transfer (LET) to benchmark RBE-model calculations. Material and methods The rat spinal cord was irradiated with 6 fractions of carbon ions at 6 positions within a 6 cm spread-out Bragg-peak (SOBP, LET: 16–99 keV/μm). TD50-values (dose at 50% complication probability) were determined from dose-response curves for the endpoint radiation induced myelopathy (paresis grade II) within 300 days after irradiation. Based on TD50-values of 15 MV photons, RBE-values were calculated and adding previously published data, the LET and fractional dose-dependence of the RBE was used to benchmark the local effect model (LEM I and IV). Results At six fractions, TD50-values decreased from 39.1 ± 0.4 Gy at 16 keV/μm to 17.5 ± 0.3 Gy at 99 keV/μm and the RBE increased accordingly from 1.46 ± 0.05 to 3.26 ± 0.13. Experimental α/β-ratios ranged from 6.9 ± 1.1 Gy to 44.3 ± 7.2 Gy and increased strongly with LET. Including all available data, comparison with model-predictions revealed that (i) LEM IV agrees better in the SOBP, while LEM I fits better in the entrance region, (ii) LEM IV describes the slope of the RBE within the SOBP better than LEM I, and (iii) in contrast to the strong LET-dependence, the RBE-deviations depend only weakly on fractionation within the measured range. Conclusions This study extends the available RBE data base to significantly lower fractional doses and performes detailed tests of the RBE-models LEM I and IV. In this comparison, LEM IV agrees better with the experimental data in the SOBP than LEM I. While this could support a model replacement in treatment planning, careful dosimetric analysis is required for the individual patient to evaluate potential clinical consequences.

Relative biological effectiveness in a proton spread-out Bragg peak formed by pencil beam scanning mode

2017 ◽  
Vol 40 (2) ◽  
pp. 359-368 ◽  
Author(s):  
Anna Michaelidesová ◽  
Jana Vachelová ◽  
Monika Puchalska ◽  
Kateřina Pachnerová Brabcová ◽  
Vladimír Vondráček ◽  
...  
Keyword(s):  
Bragg Peak ◽  
Relative Biological Effectiveness ◽  
Pencil Beam ◽  
Beam Scanning ◽  
Pencil Beam Scanning ◽  
Biological Effectiveness ◽  
Spread Out Bragg Peak

scholarly journals Therapeutic Efficacy of Variable Biological Effectiveness of Proton Therapy in U-CH2 and MUG-Chor1 Human Chordoma Cell Death

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 6115
Author(s):  
Prerna Singh ◽  
John Eley ◽  
Nayab Mahmood ◽  
Binny Bhandary ◽  
Tijana Dukic ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Cell Death ◽  
Radiation Therapy ◽  
Cell Lines ◽  
Bragg Peak ◽  
Proton Radiation ◽  
Linear Quadratic ◽  
Beam Radiation ◽  
Biological Effectiveness ◽  
Spread Out Bragg Peak

Background: Chordoma is a cancer of spinal cord, skull base, and sacral area. Currently, the standard of care to treat chordoma is resection followed by radiation therapy. Since, chordoma is present in the spinal cord and these are very sensitive structures and often complete removal by surgery is not possible. As a result, chordoma has a high chance of recurrence and developing resistance to radiation therapy. In addition, treatment of chordoma by conventional radiation therapy can also damage normal tissues surrounding chordoma. Thus, current therapeutic options to treat chordoma are insufficient and novel therapies are desperately needed to treat locally advanced and metastatic chordoma. (2) Methods: In the present investigation, human chordoma cell lines of sacral origin MUG-Chor1 and U-CH2 were cultured and irradiated with Proton Beam Radiation using the clinical superconducting cyclotron and pencil-beam (active) scanning at Middle and End of the Spread-Out Bragg Peak (SOBP). Proton radiation was given at the following doses: Mug-Chor1 at 0, 1, 2, 4, and 8 Gy and U-CH2 at 0, 4, 8, 12, and 16 Gy. These doses were selected based on a pilot study in our lab and attempted to produce approximate survival fractions in the range of 1, 0.9, 0.5, 0.1, and 0.01, respectively, chosen for linear quadratic model fitting of the dose response. (3) Results: In this study, we investigated relative biological effectiveness (RBE) of proton radiation at the end of Spread Out Bragg Peak assuming that the reference radiation is a proton radiation in the middle of the SOBP. We observed differences in the survival of both Human chordoma cell lines, U-CH2 and MUG-Chor1. The data showed that there was a significantly higher cell death at the end of the Bragg peak as compared to middle of the Bragg peak. Based on the linear quadratic (LQ) fit for cell survival we calculated the RBE between M-SOBP and E-SOBP at 95% CI level and it was observed that RBE was higher than 1 at E-SOBP and caused significantly higher cell killing. Proton field at E-SOBP caused complex DNA damage in comparison to M-EOBP and the genes such as DNA topoisomerase 1, GTSE1, RAD51B were downregulated in E-SOBP treated cells. Thus, we conclude that there seems to be substantial variation in RBE (1.3–1.7) at the E-SOBP compared with the M-SOBP.

Sensitivity analysis of the relative biological effectiveness predicted by the local effect model

2013 ◽  
Vol 58 (19) ◽  
pp. 6827-6849 ◽  
Author(s):  
T Friedrich ◽  
R Grün ◽  
U Scholz ◽  
T Elsässer ◽  
M Durante ◽  
...  
Keyword(s):  
Sensitivity Analysis ◽  
Relative Biological Effectiveness ◽  
Local Effect ◽  
Effect Model ◽  
Biological Effectiveness

Calculation of the Depth Dependence of Relative Biological Effectiveness For Clinical Proton Beams

2019 ◽  
pp. 5-10
Author(s):  
А. Белоусов ◽  
A. Belousov ◽  
Р. Бахтиозин ◽  
R. Bahtiosin ◽  
М. Колыва­нова ◽  
...  
Keyword(s):  
Bragg Peak ◽  
Relative Biological Effectiveness ◽  
Complex Function ◽  
Absorbed Dose ◽  
High Energy ◽  
Clinical Value ◽  
Proton Beams ◽  
Depth Dependence ◽  
Biological Effectiveness ◽  
The Impact

Purpose: Accurate establishing the value of relative biological effectiveness (RBE) for high energy protons is one of the main challenges of modern radiotherapy. The purpose of the study is to calculate the depth dependence of RBE for proton beams forming a spread-out Bragg peak. Material and methods: Spatial distributions of absorbed dose and dose-average linear energy transfer (LET) for 50-100 MeV (0.5 MeV energy step) monochromatic proton beams were obtained by Monte-Carlo computer simulation using Geant4 software. A linear dependence of RBE on the dose-average LET was used. Absorbed dose distributions were obtained in a water phantom for monochromatic pencil proton beams of 2.5 mm radius. The absorbed dose and the dose-average LET values were calculated in voxels with dimensions of 2×2×0.2 mm. Results: Calculations of depth dependencies of absorbed dose and dose-average LET for 50–100 MeV monochromatic proton beams were performed. Depth dependencies of RBE for these beams were established. The weighing coefficients values allowing to generate uniformspread-out Bragg peak (SOBP) were determined. Depth distribution of “RBE-weighted” dose and RBE values for SOBP were found. Conclusion: The impact of the initial beam energy step on the degree of homogeneity of the modified Bragg curve was investigated. It was shown that a step up to 1.5 MeV is acceptable for generate a smooth Bragg curve. The depth dependence of the average RBE value is a complex function, which rapidly changes especially at the far end of the SOBP. RBE may vary up to 10-30 % compared to current clinical value. The linear model of RBE-LET dependence shown in the study can be easily used in dosimetric planning systems, that may will significantly improve the quality of proton radiotherapy.

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