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Investigating the implications of a variable RBE on proton dose fractionation across a clinical pencil beam scanned spread-out Bragg peak.

Marshall, T I*; Chaudhary, P*; Michaelidesova, A*; Vechelova, J*; Davidkova, M*; Vondracek, V*; Schettino, G; Prise, K M* (2016) Investigating the implications of a variable RBE on proton dose fractionation across a clinical pencil beam scanned spread-out Bragg peak. Int. J. Radiat. Oncol. Biol. Phys., 95 (1). pp. 70-77.

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Purpose: To investigate the clinical implications of a variable Relative Biological Effectiveness (RBE) on proton dose fractionation. Using acute exposures, the current clinical adoption of a generic, constant cell killing RBE has been shown to underestimate the effect of the sharp increase in Linear Energy Transfer (LET) in the distal regions of the Spread Out Bragg Peak (SOBP). However, experimental data for the impact of dose fractionation in such scenarios is still limited.
Methods and Materials: Human fibroblasts (AG01522) at four key depth positions on a clinical SOBP of maximum energy 219.65 MeV were subject to various fractionation regimes with an inter-fraction period of 24 hours at XXX in YYY. Cell killing RBE variations were measured using standard clonogenic assays and were further validated using Monte Carlo simulations and parameterized using a Linear-Quadratic formalism.
Results: Significant variations in the cell killing RBE for fractionated exposures along the proton dose profile were observed. RBE increased sharply towards the distal position, corresponding to a reduction in cell sparing effectiveness of fractionated proton exposures at higher LET. The effect is more pronounced at smaller doses per fraction. Experimental survival fractions were adequately predicted using a Linear Quadratic formalism assuming full repair between fractions. Data were also used to validate a parameterized variable RBE model based on linear alpha parameter response with LET that showed considerable deviations from clinically predicted isoeffective fractionation regimes.
Conclusions: The biologically effective dose calculated using the clinically adopted generic RBE of 1.1 significantly underestimates the biological effective dose from variable RBE particularly in fractionation regimes with low doses per fraction. Coupled with an increase in effective range in fractionated exposures, the study indicates the needs for the optimization of proton therapy and highlights possible caveats in the move towards hypofractionation.

Item Type: Article
Subjects: Ionising Radiation
Ionising Radiation > Dosimetry
Identification number/DOI: 10.1016/j.ijrobp.2016.02.029
Last Modified: 02 Feb 2018 13:13
URI: http://eprintspublications.npl.co.uk/id/eprint/7098

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