S1735
Physics - Dose prediction/calculation, optimisation and applications for particle therapy planning
ESTRO 2026
References: 1.Kuipers S, et al. “Dosimetric impact of bone marrow sparing for robustly optimized IMPT for locally advanced cervical cancer.” Radiotherapy and Oncology. 2024;191:110222.2.Gort E et al. “Inter - fraction motion robustness and organ sparing potential of proton therapy for cervical cancer.” Radiother Oncol. 2020;152:139 - 146. 3.Corbeau A et al. “PROTECT: Prospective Phase - II - Trial Evaluating Adaptive Proton Therapy for Cervical Cancer to Reduce the Impact on Morbidity and the Immune System.” Cancers. 2021;13(20):5179. Keywords: cervical cancer, NTCP, hematologic adverse event Mini-Oral 2477 A Biomolecular Methodology to Incorporate LET Effects in Radiation Dosimetry Mohammad Rezaee 1 , Erik Traneus 2 , Johns Wong 1 1 Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins School of Medicine, Baltimore, USA. 2 Research and Development, RaySearch Laboratories, Stockholm, Sweden Purpose/Objective: Traditional radiation dosimetry relies on measuring ionization energy to determine absorbed dose in Gray (Gy), referenced to a water-equivalent medium for biological relevance. However, Gy alone is insufficient to describe the complex, medium-dependent physico- chemical and biological processes that govern biological outcomes. Empirical factors such as RBE for LET-effect1 and FMF for FLASH-RT2 have been used to supplement Gy, but they provide only simplified and limited account of biological effects. Here, we introduce the concept of a biomolecular dosimeter as a novel framework to bridge the gap between physical dose and biological effect, thereby eliminating the reliance on empirical modifiers. A new unit, Molecular Dosimetry Unit (MoD),is defined to quantify damage potential of ionizing radiation on a biologically relevant entity, independent of confounding cellular repair processes. Material/Methods: Analogues to Gy as the product of particle fluence and stopping-power, MoD is modeled as the product of Alteration Multiplicity (MA), representing number of molecular alterations in short segments of cell-free DNA, and the frequency of that multiplicity (fMA). Utility of MoD was evaluated through (1) re-analysis of published cell-survival data across a wide range of LETs, including photon, proton, alpha, and carbon-ion beams, and (2) application in treatment planning for low- and high-LET radiations using RayStation-IonPG TPS. MA and fMA were calculated by Monte-Carlo
simulation of ionization events and radical productions, and published DNA-damage yield data, within a nucleus-sized volume (8 μ m3) containing 2.2x108nanometric subvolumes of 15 DNA base-pair hydrated with 20 H2O per nucleotide3. Results: Results demonstrate that disparate survival curves as a function of Gy4,5 can be consolidated into a single curve plotted as a function of MoD, regardless of dose or LET. Figure 1 illustrates this unifying effect in Chinese hamster V79 cell line. Similar results are observed for other animal and human cell lines. Furthermore, comparison of depth-dose and depth- MoD distributions in a proton spread-out Bragg Peak (Figure 2) shows that, while dose remain uniform, MoD increases gradually with depth and peaks noticeably at the distal edge, with potential impact on biological outcomes in this region.
Conclusion: The MoD unit shows promise in consolidating
radiobiological responses across varying LETs without the need for RBE correction and in incorporating beam LET-effect directly into treatment planning. These capabilities enable more accurate dose prescriptions and improved prediction of biological effects in radiotherapy. Ongoing investigations focus on experimental measurement of MA and fMA, and further refinement of MoD model for validation and incorporation of dose-rate effects. References: 1- Paganetti H, et.al. Relative biological effectiveness (RBE) values for proton beam therapy. Int J Radiat Oncol Biol Phys. 2002;53(2):407.2- Böhlen TT, et.al. Normal Tissue Sparing by FLASH as a Function of Single-Fraction Dose: A Quantitative Analysis. Int J Radiat Oncol Biol Phys. 2022;114(5):1032. 3- Rezaee M, Adhikary A. The Effects of Particle LET and Fluence on the Complexity and Frequency of Clustered DNA
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