Ionization detail parameters and cluster dose: a mathematical model for selection of nanodosimetric quantities for use in treatment planning in charged particle radiotherapy

Abstract

Objective: To propose a mathematical model for applying Ionization Detail (ID), the detailed spatial distribution of ionization along a particle track, to proton and ion beam radiotherapy treatment planning (RTP). Approach: Our model provides for selection of preferred ID parameters (Ip ) for RTP, that associate closest to biological effects. Cluster dose is proposed to bridge the large gap between nanoscopic Ip and macroscopic RTP. Selection of Ip is demonstrated using published cell survival measurements for protons through argon, comparing results for nineteen Ip : Nk ; k = 2,3,...,10, the number of ionizations in clusters of k or more per particle, and Fk ; k = 1,2,...,10, the number of clusters of k or more per particle. We then describe application of the model to ID-based RTP and propose a path to clinical translation. Main results: The preferred Ip were N4 and F5 for aerobic cells, N5 and F7 for hypoxic cells. Significant differences were found in cell survival for beams having the same LET or the preferred Nk . Conversely, there was no significant difference for F5 for aerobic cells and F7 for hypoxic cells, regardless of ion beam atomic number or energy. Further, cells irradiated with the same cluster dose for these Ip had the same cell survival. Based on these preliminary results and other compelling results in nanodosimetry, it is reasonable to assert that Ip exist that are more closely associated with biological effects than current LET-based approaches and microdosimetric RBE-based models used in particle RTP. However, more biological variables such as cell line and cycle phase, as well as ion beam pulse structure and rate still need investigation. Significance: Our model provides a practical means to select preferred Ip from radiobiological data, and to convert Ip to the macroscopic cluster dose for particle RTP.

Ionization Detail Parameters for DNA Damage Evaluation in Charged Particle Radiotherapy: Simulation Study Based on Cell Survival Database

“…Therefore, finding the most accurate p and d combination requires at least a general knowledge of the size of DNA fragments important in the context of interactions with ionizing radiation and a sensible approach to assessing the resulting p value based on the chosen d. For that reason, these studies focus on R 2 for a target of 2.3 × 3.4 nm 2 . Basing on R 2 is not contrary to the approach proposing ionization details [7]. It presents the opportunity to enhance this approach using the proposed universal descriptor R 2 .…”

“…We completed simulations for target sizes of (1) diameters equal to height of 0.8, 1.0, 1.3, 1.5, 1.8, 2.0, 2.3 and 2.5 nm, (2) diameters of 1.0, 2.0, and 2.3 nm, and height/diameter ratio of 1.48. The source was a pencil beam of 1 H, 4 He, 7 Li, 11 B, 12 C, 14 N, 16 O, 28 Si to provide various radiation qualities and consistency with radiobiological data. Since Geant4-DNA can only simulate ionization caused by incident ions predominant in the cosmic spectrum, direct results for 20 Ne were not available, leading to interpolation using 12 C, 14 N, 16 O, and 28 S. The interpolation method was tested for 16 O using 12 C, 14 N, and 28 S, yielding very good agreement with the result of the direct simulation for 16 O.…”

“…With the ongoing development of nanodosimetric techniques supported with Monte Carlo (MC) simulations, it presents a valuable opportunity to improve the future planning of charged particle radiotherapy by considering ionization details. The evolving understanding of proton and ion radiobiology requires a more nuanced approach compared to current clinical methods relying on LET and RBE for charged particle radiotherapy; therefore, a formalism based on ionization detail parameters and cluster dose instead of current LET-and RBE-based models has been proposed for use in particle radiotherapy treatment planning [7]. For several years, researchers have been focusing on the nanodosimetric quantity expressing the probability of formation of the ionization clusters and its parameters for DNA damage evaluation.…”

“…In many studies, the potential use of F k was evaluated [6,7,9,10]. F 2 was chosen as the first quantity to assess because of the requirement for at least two ionizations leading to DSB.…”

Lithium inelastic cross-sections and their impact on micro and nano dosimetry of boron neutron capture

“…The I p considered in this study have been shown to closely associate with different biological endpoints independently of the particle; N 1 with cell inactivation cross-sections (Conte et al 2017), F 2 with DSB cross-sections (Nettelbeck and Rabus 2011), F 5 and F 7 with cell survival in aerobic and hypoxic conditions, respectively (Faddegon et al 2023).…”