UCSF

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 (I_p) for RTP, that associate closest to biological effects. Cluster dose is proposed to bridge the large gap between nanoscopicI_pand macroscopic RTP. Selection ofI_pis demonstrated using published cell survival measurements for protons through argon, comparing results for nineteenI_p:N_k,k= 2, 3, …, 10, the number of ionizations in clusters ofkor more per particle, andF_k,k= 1, 2, …, 10, the number of clusters ofkor more per particle. We then describe application of the model to ID-based RTP and propose a path to clinical translation.Main results. The preferredI_pwereN₄andF₅for aerobic cells,N₅andF₇for hypoxic cells. Significant differences were found in cell survival for beams having the same LET or the preferredN_k. Conversely, there was no significant difference forF₅for aerobic cells andF₇for hypoxic cells, regardless of ion beam atomic number or energy. Further, cells irradiated with the same cluster dose for theseI_phad the same cell survival. Based on these preliminary results and other compelling results in nanodosimetry, it is reasonable to assert thatI_pexist 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 preferredI_pfrom radiobiological data, and to convertI_pto the macroscopic cluster dose for particle RTP.