Brainstem Toxicity in Pediatric Patients Receiving Cranial Radiotherapy with Protons: A Single Institution Experience

Abstract

Asymptomatic post-radiation brainstem imaging changes (CTCAE version 5 Grade I toxicity) following proton beam therapy (PBT) have been reported as high as 20-30% incidence in some series while symptomatic brainstem injury is rarer, with an incidence of 2-7% in the literature. These findings have led to consensus statements and recommendations for brainstem dosimetric goals for patients receiving PBT. We retrospectively reviewed the incidence of post-PBT brainstem imaging changes and injury following cranial PBT utilizing a gantry-mounted synchrocyclotron single vault system. Patients ≤ 21 years of age who received a minimum 0.1cc max brainstem dose of 50 cobalt-Gray equivalents (CGE) were eligible for analysis. Patients were assessed for “central nervous system necrosis” in the brainstem per CTCAE v5.0 criteria. All patients were followed clinically and radiographically for ≥ 1 year after completing PBT. Analysis included brainstem doses exceeding University of Florida brainstem goal and max constraints. Between 2013 and 2018, 58 patients with a median age of 10.3 years (range 1–21.9 years) were included for analysis. The median radiation dose was 54 CGE (50.4–60 CGE). 36.2% of patients were treated with craniospinal radiation, 71.4% received 23.4 CGE and 23.4% received 36 CGE. 22.4% received pre-radiation chemotherapy, 32.8% received concurrent chemotherapy, and 34% received adjuvant chemotherapy. 3.4% received myeloablative chemotherapy with stem cell rescue. The percentage of patients exceeding the University of Florida goal and max brainstem constraints are presented in Table I. Two patients (3.4%) demonstrated evidence of radiographic changes consistent with CTCAE Version 5.0 Grade 1 toxicity. Both of these patients received pre-PBT myeloablative chemotherapy with stem cell rescue. There were no patients with CTCAE Version 5.0 Grade ≥ 2 brainstem injury. No symptomatic brainstem injury observed in pediatric patients treated using a gantry-mounted synchrocyclotron proton system despite exceeding previously recommended dose constraints. The incidence of post-radiation asymptomatic radiographic changes in the brainstem was lower than previous publications of grade I toxicity. While goal and max D50% were commonly exceeded, no patients exceeded the 0.1cc max constraint suggesting this may be more predictive of brainstem toxicity.Abstract 2532; TableGOAL 0.1cc Max > 56.6MAX 0.1cc Max > 58GOAL D10% > 55.4MAX D10% > 56GOAL D50% > 52.4MAX D50% > 54% Exceeded8.6%013.8%1.7%39.7%15.5% Open table in a new tab