Clinical outcomes and quality of life in children and adolescents with primary brain tumors treated with pencil beam scanning proton therapy

Background Long-term treatment-related toxicity may substantially impact well-being, quality of life (QoL), and health of children/adolescents with brain tumors (CBTs). Strategies to reduce toxicity include pencil beam scanning (PBS) proton therapy (PT). This study aims to report clinical outcomes and QoL in PBS-treated CBTs. Procedure We retrospectively reviewed 221 PBS-treated CBTs aged <18 years. Overall-free (OS), disease-free (DFS), and late-toxicity-free survivals (TFS), local control (LC) and distant (DC) brain/spinal control were calculated using Kaplan-Meier estimates. Prospective QoL reports from 206 patients (proxies only <= 4 years old [yo], proxies and patients >= 5 yo) were descriptively analyzed. Median follow-up was 51 months (range, 4-222). Results Median age at diagnosis was 3.1 years (range, 0.3-17.7). The main histologies were ependymoma (n = 88; 39.8%), glioma (n = 37; 16.7%), craniopharyngioma (n = 22; 10.0%), atypical teratoid/rhabdoid tumor (ATRT) (n = 21; 9.5%) and medulloblastoma (n = 15; 6.8%). One hundred sixty (72.4%) patients received chemotherapy. Median PT dose was 54 Gy(relative biological effectiveness) (range, 18.0-64.8). The 5-year OS, DFS, LC, and DC (95% CI) were 79.9% (74-85.8), 65.2% (59.8-70.6), 72.1% (65.4-78.8), and 81.8% (76.3-87.3), respectively. Late PT-related >= G3 toxicity occurred in 19 (8.6%) patients. The 5-year >= G3 TFS was 91.0% (86.3-95.7). Three (1.4%) secondary malignancies were observed. Patients aged <= 3 years at PT (P = .044) or receiving chemotherapy (P = .043) experienced more >= G3 toxicity. ATRT histology independently predicted distant brain failure (P = .046) and death (P = .01). Patients aged >= 5 years self-rated QoL higher than their parents (proxy assessment). Both reported lower social functioning and cognition after PT than at baseline, but near-normal long-term global well-being. QoL was well below normal before and after PT in children <= 4 years. Conclusions The outcome of CBTs was excellent after PBS. Few patients had late >= G3 toxicity. Patients aged <5 years showed worse QoL and toxicity outcomes.