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Relative Biological Effectiveness of Double-Strand Break Induction for Modeling Cell Survival in Pristine Proton Beams of Different Dose-Averaged Linear Energy Transfers

C Peeler

C Peeler1,2*, R Taleei1 , F Guan1 , L Bronk1,2 , D Patel1 , U Titt1 , D Mirkovic1 , R Stewart3 , D Grosshans1 , R Mohan1 , (1) UT MD Anderson Cancer Center, Houston, TX, (2) UT Graduate School of Biomedical Sciences at Houston, Houston, TX, (3) University of Washington School of Medicine, Seattle, WA


SU-F-BRD-16 (Sunday, July 12, 2015) 4:00 PM - 6:00 PM Room: Ballroom D

Purpose: High throughput in vitro experiments assessing cell survival following proton radiation indicate that both the alpha and the beta parameters of the linear quadratic model increase with increasing proton linear energy transfer (LET). We investigated the relative biological effectiveness (RBE) of double-strand break (DSB) induction as a means of explaining the experimental results.

Methods: Experiments were performed with two lung cancer cell lines and a range of proton LET values (0.94 – 19.4 keV/μm) using an experimental apparatus designed to irradiate cells in a 96 well plate such that each column encounters protons of different dose-averaged LET (LETd). Traditional linear quadratic survival curve fitting was performed, and alpha, beta, and RBE values obtained. Survival curves were also fit with a model incorporating RBE of DSB induction as the sole fit parameter. Fitted values of the RBE of DSB induction were then compared to values obtained using Monte Carlo Damage Simulation (MCDS) software and energy spectra calculated with Geant4. Other parameters including alpha, beta, and number of DSBs were compared to those obtained from traditional fitting.

Results: Survival curve fitting with RBE of DSB induction yielded alpha and beta parameters that increase with proton LETd, which follows from the standard method of fitting; however, relying on a single fit parameter provided more consistent trends. The fitted values of RBE of DSB induction increased beyond what is predicted from MCDS data above proton LETd of approximately 10 keV/μm.

Conclusion: In order to accurately model in vitro proton irradiation experiments performed with high throughput methods, the RBE of DSB induction must increase more rapidly than predicted by MCDS above LETd of 10 keV/μm. This can be explained by considering the increased complexity of DSBs or the nature of intra-track pairwise DSB interactions in this range of LETd values.

Funding Support, Disclosures, and Conflict of Interest: NIH Grant 2U19CA021239-35

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