Abstract
The physical properties of particles used in radiation therapy, such as protons, have been well characterized, and their dose distributions are superior to photon-based treatments. However, proton therapy may also have inherent biologic advantages that have not been capitalized on. Unlike photon beams, the linear energy transfer (LET) and hence biologic effectiveness of particle beams varies along the beam path. Selective placement of areas of high effectiveness could enhance tumor cell kill and simultaneously spare normal tissues. However, previous methods for mapping spatial variations in biologic effectiveness are time-consuming and often yield inconsistent results with large uncertainties. Thus the data needed to accurately model relative biological effectiveness to guide novel treatment planning approaches are limited. We used Monte Carlo modeling and high-content automated clonogenic survival assays to spatially map the biologic effectiveness of scanned proton beams with high accuracy and throughput while minimizing biological uncertainties. We found that the relationship between cell kill, dose, and LET, is complex and non-unique. Measured biologic effects were substantially greater than in most previous reports, and non-linear surviving fraction response was observed even for the highest LET values. Extension of this approach could generate data needed to optimize proton therapy plans incorporating variable RBE.
Highlights
The physical properties of particles used in radiation therapy, such as protons, have been well characterized, and their dose distributions are superior to photon-based treatments
The spatial energy spectra, and the linear energy transfer (LET) spectra, of a therapeutic proton beam depend on several factors including incident energy, spread-out Bragg peak (SOBP) width, and position of measurement within the SOBP as well as the machinespecific hardware used for scattering and range modulation
To minimize the breadth of the energy and LET spectra, and to facilitate correlations of biologic effect with LET and dose, we developed a system using monoenergetic scanned proton beams
Summary
The physical properties of particles used in radiation therapy, such as protons, have been well characterized, and their dose distributions are superior to photon-based treatments. Measured biologic effects were substantially greater than in most previous reports, and non-linear surviving fraction response was observed even for the highest LET values Extension of this approach could generate data needed to optimize proton therapy plans incorporating variable RBE. A large amount of research has demonstrated that particles generally have higher relative biological effectiveness (RBE) than photons (which by definition have an RBE of 1 when produced by Cobalt-60) towards the end of their range This increased RBE indicates that particles are more biologically effective at inducing cell death than are photons, which underscores their potential for treating radiation-resistant tumors[4,5]. In the current clinical practice of proton therapy, the RBE is assumed to have a generic, spatially invariant, constant value of 1.18 This assumption has been justified based on numerous in vitro and in vivo experiments carried out under relatively limited conditions using older delivery techniques (e.g., high doses per fraction, passive scattering)[8]. Deeper understanding of the unique biologic effects of protons, combined with advances in planning delivery techniques, could considerably expand the therapeutic index of proton therapy
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