Imaging changes with or without neurological symptoms after proton therapy in pediatric posterior fossa tumors; initial experience of the Dutch national cohort

BACKGROUND AND PURPOSE: The incidence of proton therapy (PT)-related imaging changes in the central nervous system, and associated symptoms, varies widely in literature. The aim of this study was to assess imaging changes after implementation of intensity-modulated pencil beam scanning in a national cohort of pediatric posterior fossa (PF) tumors.

MATERIALS AND METHODS: All pediatric PF tumor patients treated in the XXX with PT between 06-2018 and 12-2022 were analyzed. Patients receiving re-irradiation or a combination with photon therapy were excluded. Imaging changes were defined as new contrast enhancement on T1-weighted images or abnormal signal on T2-weighted imaging in the brain parenchyma or spinal cord, outside of the tumor bed and within the irradiated area. Associated symptoms were graded according to CTCAE v5.0.

RESULTS: Seventy-seven PF patients (median age 7.0 years) were analyzed. Median follow-up was 25 months and prescribed dose 54 GyE (range 49.6 - 59.4 GyE). At 12 months post-PT, a cumulative incidence rate of 33% contrast enhancement and 47% T2-weighted imaging changes was observed. Of all patients, 15% experienced any neurological symptoms related to these imaging changes, grade ≥2 symptoms were observed in 9%. The imaging changes were predominantly transient. Younger children, especially those <5 years, had a significantly higher risk of developing imaging changes (HR 8.64 [95%CI 3.60-20.74]) and symptoms (HR 6.97 [95%CI 1.80-26.99]). Prescribed dose ≥59.4 GyE and higher cerebellar D0.1cc and D10% were associated with an increased risk of imaging changes and associated symptoms.

CONCLUSION: The initial experience of PT for pediatric PF tumors in XXX demonstrates post-PT contrast enhancement with associated symptoms in 15% of the patients, and an increased risk in patients <5 years old and patients with a prescribed dose ≥59.4 GyE.