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Modeling RBE with other quantities than LET significantly improves prediction of in vitro cell survival for proton therapy

Med Phys. 2022 Nov 2. doi: 10.1002/mp.16029. Online ahead of print.

ABSTRACT

BACKGROUND: For proton therapy, a relative biological effectiveness (RBE) of 1.1 has broadly been applied clinically. However, as unexpected toxicities have been observed by the end of the proton tracks, variable RBE models have been proposed. Typically, the dose averaged linear energy transfer (LETd ) has been used as an input variable for these models but the way the LETd was defined, calculated or determined was not always consistent, potentially impacting the corresponding RBE value.

PURPOSE: This study compares consistently calculated LETd with other quantities as input variables for a phenomenological RBE model and attempts to determine which quantity that can best predicts proton RBE. The comparison was performed within the frame of introducing a new model for the proton RBE.

METHODS: High-throughput experimental set-ups of in vitro cell survival studies for proton RBE determination are simulated using the SHIELD-HIT12A Monte Carlo particle transport code. Together with LET, z*22 , here called effective Q (Qeff ), and Q are scored. Each quantity is calculated using the dose and track averaging methods, while the scoring includes all hadronic particles, all protons or only primaries. A phenomenological linear-quadratic based RBE model is subsequently applied to the in vitro data with the various beam quality descriptors used as input variables and the goodness of fit is determined and compared using a bootstrapping approach. Both linear and non-linear fit functions were tested.

RESULTS: Versions of Qeff and Q outperform LET with a statistically significant margin, with the best non-linear and linear fit having a relative root-mean-square-error (RMSE) for RBE2Gy ± one standard error of 1.55 ± 0.04 (Qeff, t, primary ) and 2.84 ± 0.07 (Qeff, d, primary ), respectively. For comparison, the corresponding best non-linear and linear fits for LETd, all protons had a relative RMSE of 2.07 ± 0.06 and 3.39 ± 0.08, respectively. Applying Welch’s t-test for comparing the calculated RMSE of RBE2Gy resulted in two-tailed p-values of <0.002 for all Q and Qeff quantities compared to LETd, all protons .

CONCLUSIONS: The study shows that Q or Qeff could be better RBE descriptors that dose averaged LET. This article is protected by copyright. All rights reserved.

PMID:36321465 | DOI:10.1002/mp.16029

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