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O119 / #742 - CHARACTERIZING BRAGG PEAK AND ENTRANCE BEAM RESPONSES IN MOUSE SPINAL CORDS TO SINGLE AND FRACTIONATED PROTON IRRADIATIONS
Abstract   Open access   Peer reviewed

O119 / #742 - CHARACTERIZING BRAGG PEAK AND ENTRANCE BEAM RESPONSES IN MOUSE SPINAL CORDS TO SINGLE AND FRACTIONATED PROTON IRRADIATIONS

Janet Denbeigh, Michelle Howard, Darwin Garcia, Emily Debrot, Kristin Cole, Nicholas Remmes and Chris Beltran
International journal of particle therapy, Vol.12(Supplement), pp.55-56
06/2024
DOI: 10.1016/j.ijpt.2024.100232
url
https://doi.org/10.1016/j.ijpt.2024.100232View
Published (Version of record) Open Access

Abstract

Background: The fixed proton relative biological effectiveness (RBE) of 1.1 in clinical planning may not accurately reflect proton therapy's true biological effects, particularly in late responding tissues like the spinal cord. This study investigates spinal cord tolerance to proton irradiation in mice, focusing on the impact of fractionation and position along the Bragg curve (Entrance [ENT] vs Bragg Peak [BP]) on proton-induced myelopathy. Methods: Female C57BL/6J mice (8 weeks old) received either single (n1x = 394) or multiple fraction (18x, n18x = 225) proton irradiation of their cervical spinal cords using lateral opposed radiation fields at one of two positions along the Bragg curve: ENT (dose-mean linear energy transfer [LET] = 1.2 keV/μm) and BP (LET = 6.9 keV/μm). Animals were monitored over a year for weight, mobility, and general health, with radiation-induced myelopathy as the primary endpoint. Results: RBE calculations for the ENT compared to the BP regions of the Bragg curve were derived from the dose-response model at 50% effect probability (TD50, grade II paresis), as determined via log-logistic model fitting. The RBE ratio, denoted as RBEENT/BP, was found to be 1.10 ± 0.06 (95% confidence interval, CI) for the single fraction cohort while for multi-fraction treatments, it was 1.19 ± 0.05 (95% CI). BP-treated mice exhibited a higher incidence and faster onset of paralysis compared to ENT cohorts. Conclusions: Our findings emphasize the need to consider both fractionation and LET in RBE determination for proton therapy. This study provides critical insights for refining clinical decision-making and highlights the importance of in vivo models for understanding proton-induced toxicity and mitigating patient side effects. FIGURE 1: Proton irradiation of the mouse spinal cord. (A). Representative Bragg peak proton treatment plan overlaid on a mouse CT scan. (B). Acrylic printed box with silicone lid. (C). Irradiation shelf with indexing for 6 positions. (D). Horizontal fixed proton beam with shelf. (E). Grade II paresis as experimental endpoint. FIGURE 2: Normal Tissue Complication Probability Plots. Dose-response curves of the mouse cervical spinal cord after single fraction (A) or multi fractions (B) of protons for Entrance (green) or Bragg peak (purple) positions.

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