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

Kalholm, Fredrik; Grzanka, L.; Toma-Daşu, Iuliana; Bassler, Niels

doi:10.1002/mp.16029

Cited by 13 publications

(2 citation statements)

References 24 publications

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“…As Q eff was demonstrated to correlate better with the RBE than LET does (Kalholm et al 2022), these results suggest that not only the physical dose in light ion beams can be estimated with OSLDs but also the RBE-weighted dose. A detector with such capability might be helpful for 4 He-and 12 C-ion beam radiotherapy, as a variable RBE is used clinically.…”

Section: Dosimetry In 12 C-beamsmentioning

confidence: 76%

Optically stimulated luminescence detectors for dosimetry and LET measurements in light ion beams

et al. 2023

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Objective: This work investigates the use of Al2O3:C and Al2O3:C,Mg optically stimulated luminescence (OSL) detectors to determine both the dose and the radiation quality in light ion beams. The radiation quality is here expressed through either the linear energy transfer (LET) or the closely related metric Qeff, which depends on the particle's speed and effective charge. The derived LET and Qeff values are applied to improve the dosimetry in light ion beams.Approach: OSL detectors were irradiated in mono-energetic 1H−, 4He−, 12C−, and 16O−ion beams. The OSL signal is associated with two emission bands that were separated using a pulsed stimulation technique and subjected to automatic corrections based on reference irradiations. Each emission band was investigated independently for dosimetry, and the ratio of the two emission intensities was parameterized as a function of fluence- and dose-averaged LET, as well as Qeff. The determined radiation quality was subsequently applied to correct the dose for ionization quenching.Main results: For both materials, the Qeff determinations in 1H− and 4He−ion beams are within 5 % of the Monte Carlo simulated values. Using the determined radiation quality metrics to correct the non-linear (ionization quenched) detector response leads to doses within 2 % of the reference doses. Significance: Al2O3:C and Al2O3:C,Mg OSL detectors are applicable for dosimetry and radiation quality estimations in 1H- and 4He-ions. Only Al2O3:C,Mg shows promising results for dosimetry in 12C-ions. Across both materials and the investigated ions, the estimated Qeff values were less sensitive to the ion type than the estimated LET values. The reduced uncertainties suggest new possibilities for simultaneously estimating the physical and biological dose in particle therapy with OSL detectors.

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Section: Dosimetry In 12 C-beamsmentioning

confidence: 76%

Optically stimulated luminescence detectors for dosimetry and LET measurements in light ion beams

et al. 2023

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“…Furthermore, Kalholm et al (2023) demonstrated that in vitro cell survival in proton therapy was better modeled using radiation quality metrics other than LET. Similarly, for the response of OSLDs to light ion beams, neither LET f nor LET d were found to provide the most accurate description of the radiation fields (Christensen et al 2023).…”

Section: Let Averaging Challengesmentioning

confidence: 99%

Assessment of fluence- and dose-averaged linear energy transfer with passive luminescence detectors in clinical proton beams

Domingo Muñoz,

Van Hoey,

Parisi

et al. 2024

Phys. Med. Biol.

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Objective: This work investigates the use of passive luminescence detectors to determine different types of averaged linear energy transfer (\overline{LET}) for the energies relevant to proton therapy. The experimental results are compared to reference values obtained from Monte Carlo simulations. Approach: Optically stimulated luminescence detectors (OSLDs), fluorescent nuclear track detectors (FNTDs), and two different groups of thermoluminescence detectors (TLDs) were irradiated at four different radiation qualities. For each irradiation, the fluence- (\overline{LET}f) and dose-averaged LET (\overline{LET}d) were determined. For both quantities, two sub-types of averages were calculated, either considering contributions from primary and secondary protons or from all protons and heavier charged particles. Both simulated and experimental data were used in combination with a phenomenological model to estimate the relative biological effectiveness (RBE). Main results: All types of \overline{LET} could be assessed with the detectors. The experimental determination of \overline{LET}f is in agreement with reference data obtained from simulations across all measurement techniques and types of averaging. On the other hand, \overline{LET}d can present challenges as a radiation quality metric to describe the detector response in mixed particle fields. However, excluding secondaries heavier than protons from the \overline{LET}d calculation, as their contribution to the luminescence is suppressed by ionization quenching, leads to equal accuracy between \overline{LET}f and \overline{LET}d. Assessment of RBE through the experimentally determined \overline{LET}d values agrees with independently acquired reference values, indicating that the investigated detectors can determine \overline{LET} with sufficient accuracy for proton therapy. Significance: OSLDs, TLDs, and FNTDs can be used to determine \overline{LET} and RBE in proton therapy. With the capability to determine dose through ionization quenching corrections derived from \overline{LET}, OSLDs and TLDs can simultaneously ascertain dose, \overline{LET}, and RBE. This makes passive detectors appealing for measurements in phantoms, facilitating the validation of clinical treatment plans or experiments related to proton therapy.

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

et al. 2022

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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 setups 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∗2/β2$z^{*2}/\beta ^2$, here called effective Q (Qeff), and Q are scored. Each quantity is calculated using the dose and track averaging methods, because 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 nonlinear fit functions were tested. Results Versions of Qeff and Q outperform LET with a statistically significant margin, with the best nonlinear 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 nonlinear 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.

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

Cited by 13 publications

References 24 publications

Optically stimulated luminescence detectors for dosimetry and LET measurements in light ion beams

Optically stimulated luminescence detectors for dosimetry and LET measurements in light ion beams

Assessment of fluence- and dose-averaged linear energy transfer with passive luminescence detectors in clinical proton beams

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

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