Purpose/Objective(s): Limited prospective information regarding acute toxicity in pediatric patients receiving proton radiotherapy exists, especially in light of the transition to pencil beam technology. We report factors associated with development of acute toxicity in children irradiated with scattered and pencil beam proton therapy (PRT) in the Pediatric Proton Consortium Registry (PPCR).

Materials/Methods: To ensure modern treatment techniques and similar numbers of spot-scanning and scattered proton treatment plans, patients treated from January 1, 2016 to June 30, 2017 were included. Acute toxicities in the following domains were collected as either being present or absent at the beginning and end of treatment: general, cardiac, endocrine, eye, gastrointestinal(GI), genitourinary(GU), hematologic, mouth, musculoskeletal, neurologic, psychologic, respiratory, and skin. Among patients without toxicity at baseline, the association of patient and treatment factors with presence of toxicity at the end of PRT was assessed using a chi square test, for age a two-sample T test.

Results: 422 children had toxicity data entered in at least one domain at baseline and end of PRT. Treatment modality was scattered in 155(37%), spot in 125(30%), and missing in 142(33%) patients. Median age was 9.9 years(0.5-21.9), median dose 54GyE(1.8-80), 41% of children required anesthesia for treatment, and 9% were uninsured. Disease-sites treated included craniospinal (CSI) 23%, 37% focal brain radiation (CNS), head/neck (11%), thoracic (8%), spine (5%), abdomen/pelvis (7%), extremities (2%), and other. Sites were condensed to CSI, CNS, and body for analysis. For patients with no toxicity at baseline, higher incidence of general (48%vs29%, p=0.04), endocrine(3%vs0.3%, p=0.04), GI(43%vs26%, p=0.047), hematologic (33%vs13%, p<0.01) toxicities were seen in patients without insurance. Higher incidence of cardiac (4%vs0.6%, p=0.03), GU (5%vs0%, p<0.01), hematologic (37%vs17%, p<0.01), and respiratory (18% vs 5%, p<0.01) toxicities were documented in patients requiring anesthesia for treatment. Increased hematologic toxicity was also associated with scattered PRT (32% vs 15%, p<0.01) and CSI (39% vs 21% CNS vs 18% body, p=0.04). Neurologic toxicity was more commonly seen in patients receiving CSI (27% vs 16% CNS vs 5%body, p<0.01). Younger age was associated with increased risk of GU (5.2vs10.2year, p=0.03) and respiratory (7.4vs10.4yrs, p=0.01) toxicity. There was no difference in skin toxicity between scattered and pencil beam PRT (72% vs 68%, p=0.56).

Conclusion: Our results suggest toxicities evaluated in PPCR registry capture broad differences in acute toxicity rates in children treated with proton therapy. Multivariate analysis is necessary to clarify the impact of medical and non-medical factors influencing these findings.