Spatial mapping of the biologic effectiveness of scanned particle beams: towards biologically optimized particle therapy

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.

RBE Model-Based Biological Dose Optimization for Proton Radiobiology Studies

“…We set the prescribed RBE-weighted dose level to be 3.80 Gy (RBE) within the SOBP (5-10 cm), corresponding to the reference photon dose at which the cell-surviving fraction is 10% for the H460 cell line, as presented in our previous study [18]. …”

“…We apply the photon coefficients obtained from our previous study to the RBE calculations. For the non–small cell lung cancer cell line H460 with 137 Cs photon irradiation, α x = 0.29 ± 0.016 Gy −1 , β x = 0.083 ± 0.00395 Gy −2 , and ( α / β ) x = 3.49 ± 0.255 Gy [18]. …”

“…Nevertheless, none of these models has ever been applied in any clinical proton therapy treatment planning system to date owing to the discrepancies among model predictions and between models and experimental data [16, 17]. This notwithstanding, nearly all of these models and most of the recent experimental data do not support the assumption of a constant proton RBE, but instead support the conclusion that proton RBE varies spatially with respect to the variation of dose and linear energy transfer (LET) [18, 19]. …”

“…First, most of the existing biophysical models were developed by using experimental data generated with PSPT [2], which may not accurately predict the biological consequences for scanned beams owing to the significant differences in beam characteristics between the two [18]. Second, accurate biological effect data for pristine proton beams are limited and difficult to obtain [18].…”

“…First, most of the existing biophysical models were developed by using experimental data generated with PSPT [2], which may not accurately predict the biological consequences for scanned beams owing to the significant differences in beam characteristics between the two [18]. Second, accurate biological effect data for pristine proton beams are limited and difficult to obtain [18]. Moreover, most of the experimental validations of RBE models stay at the stage of irradiating biological samples across the flat physical dose 1 SOBP; few studies have been performed under a uniform biological dose 2 SOBP, the results of which provide much stronger evidence for proving the accuracy and prediction ability of a selected RBE model.…”