Acute Toxicities During Proton Therapy with or Without Simultaneous Chemotherapy in Pediatric CNS Tumors: A Retrospective Cohort Study

<b>Background:</b> Proton beam therapy (PBT) is a valuable alternative to photon radiotherapy of CNS tumors in children and adolescents. While most recent studies deal with the outcome or long-term side effects of PBT, the aim of this study was to investigate the feasibility of PBT with a particular focus on the acute toxicity of a simultaneous radiochemotherapy (sPBCT). <b>Patients and methods:</b> We enrolled 199 children [median age 7.4 years (range, 0.9-17.9)], who received altogether 200 courses of PBT/sPBCT at initial diagnosis (<i>n</i> = 121) or at relapse (<i>n</i> = 79) with sPBCT in 52 (26%) courses. Data collection to PBT/sPBCT was based on the medical records and the KiProReg (Registry study of Standard Proton Therapy in Children at West German Proton Therapy Center) with a primarily descriptive-statistical and logistic regression analysis. <b>Results:</b> During PBT/sPBCT a total of <i>n</i> = 704 adverse events (AEs, mean 3.4 per course) were observed. Eighty-seven of them were graded as high-grade adverse events (HGAEs, Common Terminology Criteria for Adverse Eventº ≥3 (CTCAE)) which occurred in 67 (33.5%) PBT/sPBCT courses. HGAEs were in particular hematotoxicity (<i>n</i> = 43; 64.1%) and infections (<i>n</i> = 18; 26.8%). A significantly higher rate of HGAEs was documented in patients treated with sPBCT (<i>n</i> = 33/52; 63.5%) compared to those with PBT only (<i>n</i> = 34/148; 23.0%) (<i>p</i> = 0.001). In children with sPBCT, 15 (28.8%) patients could not receive the recommended dose or schedule of the planned chemotherapy (CTx) due to HGAEs, with the rate of planned CTx courses performed being significantly lower in patients receiving intensive intravenous CTx (<i>p</i> < 0.001). Interruptions of PBT and of simultaneous CTx were both significantly associated with the occurrence of infections [Odds ratios 3.002 (95% CI 1.005-8.971, <i>p</i> = 0.049) and 3.905 (95% CI 1.005-15.174, <i>p</i> = 0.049)]. Total discontinuation of treatment did not occur. <b>Conclusions:</b> Concurrent CTx during proton therapy is associated with a significant increased risk for HGAE occurrence and therapy interruptions requiring individual dose and schedule adjustments dependent on CTx intensity, very experienced interdisciplinary teams as well as intensive care and in-/out-patient oncology facilities on site.