Evaluating the Dose Rate in Patients with and without Olfactory Sensations during Cranio-Spinal Irradiation with Pencil-Beam Scanning Proton Therapy

Abstract

<h3>Purpose/Objective(s)</h3> Unusual olfactory sensation, also known as phantosmia, have been occasionally reported by pediatric patients receiving cranio-spinal irradiation (CSI) with proton beams. While observed by many groups, the causes and mitigation strategies for this phenomenon - which can induce anxiety, nausea and vomiting - are yet to be established. At our institution, reports of phantosmia during CSI with proton beams have increased after transitioning from passive scattering to pencil beam scanning (PBS) delivery. Since the dose distributions associated with both delivery methods are similar, we conducted this study to evaluate if the dose rate to the olfactory region could have an influence on the incidence of phantosmia in patients receiving CSI with PBS. <h3>Materials/Methods</h3> A representative cohort of 10 pediatric patients that received CSI with PBS at our institution between 2019 and 2020 was considered. The cohort was built to include 5 patients that reported symptoms of phantosmia during irradiation and 5 patients of similar ages and diagnosis that did not report such symptoms. An in-house developed dose rate calculation tool was used to estimate the maximum time-averaged dose rate to each voxel for any time intervals of 10 ms, 100 ms, and 1 s. The dose rate and total dose to 0.5 cc, 2%, 10%, 50%, and 95% of the volumes of the olfactory bulb and the nasal cavity was evaluated in all patients. The statistical significance of the differences between each cohort for the selected dose-volume histograms (DVH) and dose rate volume histogram (DRVH) points was assessed using a two-sample t-Test. <h3>Results</h3> We found no statistically significant differences between the symptomatic and asymptomatic groups for the DVH points of interest in the olfactory bulb or nasal cavity. In terms of dose rate, no statistically significant differences were observed in the olfactory bulb for any time interval. In the nasal cavity, however, dose rates at both 10 ms and 100 ms time intervals were substantially higher in the symptomatic group. Statistically significant differences were observed in the dose rate to 50% of the nasal cavity at the 10 ms time interval, with a mean value of 164.67 Gy/min (sd = 41.39 Gy/min) for patients that reported phantosmia compared to 108.65 Gy/min (sd = 47.98 Gy/min) for patients that did not report unusual olfactory symptoms (p = 0.0411). <h3>Conclusion</h3> In this patient cohort, phantosmia experienced during dose delivery was correlated with the peak dose rates to the nasal cavity during short time intervals. While further studies are warranted to identify potential underlying mechanisms, our findings are consistent with the hypothesis of ozone production in the nasal cavity during irradiation. We did not observe a correlation of phantosmia with dose or dose rate to the olfactory bulb, however other radiation effects in this region cannot be excluded as a potential cause.