Investigating the Implications of a Variable RBE on Proton Dose Fractionation Across a Clinical Pencil Beam Scanned Spread-Out Bragg Peak

Journal Article · Sun May 01 00:00:00 EDT 2016 · International Journal of Radiation Oncology, Biology and Physics

DOI:https://doi.org/10.1016/J.IJROBP.2016.02.029· OSTI ID:22648616

Marshall, Thomas I.; Chaudhary, Pankaj ^[1]; Michaelidesová, Anna ^[2]; Vachelová, Jana; Davídková, Marie ^[2]; Vondráček, Vladimir ^[3]; Schettino, Giuseppe ^[4]; Prise, Kevin M. ^[1]

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1. Centre for Cancer Research and Cell Biology, Queen's University, Belfast (United Kingdom)
2. Department of Radiation Dosimetry, Nuclear Physics Institute CAS, Prague (Czech Republic)
3. Proton Therapy Center Czech, Prague (Czech Republic)
4. Radiation Dosimetry, National Physical Laboratory, Teddington (United Kingdom)

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 are still limited. Methods and Materials: Human fibroblasts (AG01522) at 4 key depth positions on a clinical SOBP of maximum energy 219.65 MeV were subjected to various fractionation regimens with an interfraction period of 24 hours at Proton Therapy Center in Prague, Czech Republic. 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 toward the distal position, corresponding to a reduction in cell sparing effectiveness of fractionated proton exposures at higher LET. The effect was 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 α parameter response with LET that showed considerable deviations from clinically predicted isoeffective fractionation regimens. Conclusions: The RBE-weighted absorbed dose calculated using the clinically adopted generic RBE of 1.1 significantly underestimates the biological effective dose from variable RBE, particularly in fractionation regimens with low doses per fraction. Coupled with an increase in effective range in fractionated exposures, our study provides an RBE dataset that can be used by the modeling community for the optimization of fractionated proton therapy.

• OSTI ID: 22648616
• Journal Information: International Journal of Radiation Oncology, Biology and Physics, Vol. 95, Issue 1; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0360-3016
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRONMENTAL POLLUTANT EFFECTS ON LIVING ORGANISMS AND BIOLOGICAL MATERIALS
62 RADIOLOGY AND NUCLEAR MEDICINE
ABSORBED RADIATION DOSES
BRAGG CURVE
CELL KILLING
COMPUTERIZED SIMULATION
FRACTIONATED IRRADIATION
FRACTIONATION
LET
MEV RANGE 100-1000
MONTE CARLO METHOD
PROTON BEAMS
RBE
SURVIVAL CURVES