DOSE-DEPENDENT BRAIN DIFFUSION CHANGES AFTER HADRONTHERAPY FOR SKULL BASE AND PARANASAL SINUSES CANCERS: PRELIMINARY RESULTS OF A PROSPECTIVE MULTICENTRIC TRIAL

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Background and Aims: Range uncertainties remain a key limitation of proton therapy.To address this, the NOVO collaboration is developing a compact detector array of organic scintillator bars with dual-ended light readout, allowing simultaneous detection and imaging of prompt gamma rays (PGs) and fast neutrons (FNs) produced during treatment.Furthermore, PG energy depends on the target nuclei and therefore provides information about elemental tissue composition, potentially enabling the identification of hypoxic tumor regions.The purpose of this study was therefore to examine the impact of tissue composition on PG production and energy spectra in head-and-neck cancer (HNC). Methods:The FLUKA Monte Carlo code was utilized to simulate multiple pencil beam spots from treatment fields of HNC patients, with the generation of a voxel file enabling the simulation of patient geometries.A code tracking PGs was implemented, providing data on emitted energy spectra, production coordinates, and target and residual nuclei.To investigate the possibility of assessing hypoxia levels, additional simulations were performed for homogenous 20×20×30 cm 3 phantoms with varying oxygen concentrations and constant mass densities.Phantoms 1-5 spanned oxygen, hydrogen, and carbon mass percentages from 88.9%, 11.1%, and 0% to 70.1%, 8.8%, and 21.1%, respectively.Results: The PG energy spectra showed a clear dependence on tissue composition, with bone and adipose tissue exhibiting lower mean PG energies than surrounding tissues (Figure 1A).Tissues modelled with lower oxygen and higher carbon content demonstrated reduced overall PG production (Figure 1, B-D).In the phantom simulations, PGs originating from oxygen-related nuclear reactions, such as 16O(p,p) 16O* at 6.13 MeV and 16O(p,pα)12C* at 4.44 MeV, decreased with declining oxygen concentration (Figure 2, dashed lines).However, the total 4.44 MeV PG production rose due to increased carbon content, driven by 12C(p,p)12C* (Figure 2, solid thick lines).Despite identical mass densities, phantom 1 produced more PGs than phantom 5, indicating a strong dependence on oxygen content. Conclusions:The sensitivity of PG production to tissue composition and oxygenation indicates that distinct PG spectra are generated within HNC patients, motivating further investigation of PG spectroscopy for range verification and tissue characterization for this patient group.

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