Proton Craniospinal Irradiation Technique Influences Rate of Phantosmia in Pediatric Patients
Key findings
- This retrospective study investigated the incidence of phantosmia in 127 pediatric patients (ages 3–21) with a primary brain tumor who underwent proton craniospinal irradiation at Massachusetts General Hospital between 2016 and 2021
- Among the 59 patients who were not sedated for radiation, the incidence of phantosmia was 29%
- The incidence of phantosmia was significantly higher with the pencil beam scanning technique than with the passive scattering technique (42% vs. 4.75%; P=0.002)
- Six of the patients reporting phantosmia experienced recall of smell between radiation fractions, 15 required medication intervention for anxiety or nausea/vomiting, and two required sedation during subsequent proton therapy
- The discovery of an increase in phantosmia with more modern techniques utilizing an increased dose rate is hypothesis-forming and indicative of the importance of studying the impact of dose rate on additional outcomes following proton beam radiation
Phantosmia—olfactory hallucinations or phantom smell, usually unpleasant—during brain radiation has been reported for decades. With the advent of proton therapy, though, radiation oncologists are encountering complaints about phantosmia and associated nausea/emesis more frequently. The phenomenon seems to be particularly common in pediatric radiation oncology.
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Shannon M. MacDonald, MD, a radiation oncologist at the Mass General Cancer Center, Myrsini Ioakeim-Ioannidou, MD, a research fellow in the Department of Radiation Oncology, and colleagues retrospectively studied the rate of phantosmia among pediatric patients treated with proton craniospinal irradiation (CSI) at Mass General.
In Pediatric Blood & Cancer, they report a high incidence, plus a novel finding that the proton technique significantly influences olfactory perception.
Methods
The researchers analyzed data on 127 patients ≤21 years old who received proton CSI and a boost to the brain for a primary brain tumor between 2016 and 2021. Fifty-nine patients did not have sedation planned (mean age, 15 years; range, 8–21 years).
Twenty-one patients in the non-sedated group were treated with the passive scattering (PS) technique and 38 with the pencil beam scanning (PBS) technique (single posterior–anterior field, n=23; two lateral fields, n=15).
Incidence of Phantosmia
Seventeen patients in the non-sedated group (29%), ages eight to 17, reported phantosmia. The rate varied by treatment technique:
- 42% with PBS vs. 4.75% with PS (P=0.002)
- Within the PBS group: 48% with single field vs. 33% with two fields (P=0.506)
The incidence of nausea/vomiting did not vary by treatment technique.
Phantosmia-related Variables
Phantosmia was described as a "bad/foul/horrible" smell, "chlorinated decaying fish," "a dirty bathroom," or "chlorine smell." Six of the patients reporting phantosmia experienced recall of smell between CSI fractions. Fifteen required an anti-anxiety agent, oral antiemetic, and/or appetite stimulant, and two required sedation during subsequent proton therapy.
Commentary
This is the first study to describe a significant association of phantosmia with the proton beam technique used. The reason for the differing rates is unclear, but dose, dose rate and linear energy transfer may differ somewhat between PS and PBS.
A prospective multicenter trial is needed to evaluate the effect of these variables during proton therapy and determine how to minimize the occurrence of phantosmia.
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