Factors Associated with Acute Toxicity in Pediatric Patients Treated with Proton Radiotherapy: A Report from the Pediatric Proton Consortium Registry.

Limited prospective information regarding acute toxicity in pediatric patients receiving proton therapy (PT) exists. In this study, Pediatric Proton Consortium Registry (PPCR) data was analyzed for factors associated with development of acute toxicity in children receiving passively scattered or pencil beam scanning PT.Pediatric patients treated with PT and enrolled on the PPCR from 2016-2017 at seven institutions were included. Data was entered on presence versus absence of acute general, cardiac, endocrine, eye, gastrointestinal (GI), genitourinary, hematologic, mouth, musculoskeletal, neurologic, psychologic, respiratory, and skin toxicities prior to (baseline) and at the end of PT (acute). Associations between patient and treatment variables with development of acute toxicity were assessed with multivariable modelling.Of 422 patients included, PT technique was passively scattered in 241 (57%), pencil beam scanning in 180 (43%), and missing in 1 (<1%) patient. Median age was 9.9 years. Daily anesthesia for treatment was used in 169 (40%). Treatments were categorized as craniospinal irradiation (CSI) (n=100, 24%), focal CNS PT (n=157, 38%), or body PT (n=158, 38%). Passively scattered PT was associated with increased risk of hematologic toxicity compared to pencil beam scanning PT (OR: 3.03, 95% CI: 1.38-6.70, p=0.006). There were no other differences toxicities between PT techniques. Uninsured patients had increased risk of GI (OR: 2.71, 1.12-6.58, p=0.027) and hematologic toxicity (OR: 10.67, 2.68-42.46, p<0.001). Patients receiving concurrent chemotherapy were more likely to experience skin (OR: 2.45, 1.23-4.88, p=0.011), hematologic (OR: 2.87, 1.31-6.25, p=0.008), GI (OR: 2.37, 1.33-4.21, p=0.003), and mouth toxicities (OR: 2.03, 1.10-3.73, p=0.024). Patients receiving 49-55 Gy were more likely to experience skin (OR: 2.18, 1.06-4.44, p=0.033) toxicity than those receiving <49 Gy.The PPCR registry highlights broad differences in acute toxicity rates in children receiving PT, and identifies opportunities for improvements in prevention, monitoring, and treatment of toxicities.