DOSE RESPONSE RELATIONSHIP OF OZONE GENERATION DURING PROTON IRRADIATION WITH EXPERIMENTAL INSIGHTS INTO OLFACTORY SENSATIONS

Kurzfassung

Background and Aims Unpleasant odors during radiotherapy are a common, burdensome, but poorly understood phenomenon, which may result in intolerance to treatment. Ozone formation by ionizing radiation is a suspected cause, because of its low odor threshold around 7 parts per billion (ppb). While ozone formation was studied with e.g., clinical linear accelerators and alpha-particle radiation, this study presents the first systematic investigation of proton-induced ozone production and its dose dependence in the clinical environment of a proton therapy center with the aim of improving patients’ overall treatment adherence. Methods Ozone measurements were performed with a commercial ozone monitor based on differential ultraviolet light (254 nm) absorption and using dual-cell detection. Air was sampled at 1.8 L/min through a coiled tube (1.25 m length, 10 cm coil diameter, 3.7 mm inner tube diameter) placed in a 10 x 10 cm² irradiation field of a spot scanning multi-room proton machine. Two irradiation series were performed: (i) fixed energy of 100 MeV (13.7 MeV residual energy) with varying machine output (1.43–28.55 Gy absorbed dose in the isocenter) and (ii) fixed machine output with energies of 100–140 MeV (residual energies 13.7-90.8 MeV; doses 2.05-5.71 Gy), using a 7.5 cm polymethylmethacrylate (PMMA) range shifter. The relation between time-integrated ozone readings and peak ozone readings, respectively, was compared with the applied absorbed dose. Monte Carlo simulations of the dose distributions were conducted with a clinical treatment planning system. Results Ozone measurements demonstrated that ozone concentrations increase linearly with dose under both, varying machine output and changing beam energy. At a fixed residual energy of 13.7 MeV, ozone concentrations ranged from 6 to 23 ppb as machine output increased. Both, integrated ozone concentration signals (R²=0.999) and maximal values (R²=0.862) were dose-dependent. When beam energy was varied (residual energies 13.7-90.8 MeV), decreasing energies enhanced ozone formation, with ozone concentration maxima ranging from 17.5 to 8 ppb (gradient=2.22 ppb/Gy). Again, integrated signals and peaks scaled linearly with dose. Conclusions Measured ozone concentrations were near the human detection threshold, thus ozone and ozone reaction products such as saturated and unsaturated aldehydes should be considered as possible causes of burdensome olfactory sensations during radiotherapy.