Imaging Changes With or Without Neurologic Symptoms After Proton Therapy in Pediatric Posterior Fossa Tumors: Initial Experience of the Dutch National Cohort

Abstract

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.

Methods and materials: All pediatric PF tumor patients treated in the Netherlands with PT between June 2018 and December 2022 were analyzed. Patients receiving reirradiation 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 National Cancer Institute Common Terminology Criteria for Adverse Events 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 aged <5 years, had a significantly higher risk of developing imaging changes (hazard ratio, 8.64; 95% CI, 3.60-20.74) and symptoms (hazard ratio, 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.

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