Department of Radiation Oncology, Geneva University Hospital, Geneva, Switzerland.
Department of Radiation Oncology, University College London Hospitals, London, United Kingdom.
Pediatr Blood Cancer. 2020 Dec;67(12):e28465. doi: 10.1002/pbc.28465. Epub 2020 Sep 9.
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.
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).
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.
The outcome of CBTs was excellent after PBS. Few patients had late ≥G3 toxicity. Patients aged <5 years showed worse QoL and toxicity outcomes.
长期治疗相关的毒性可能会极大地影响患有脑肿瘤（CBT）的儿童/青少年的幸福感、生活质量（QoL）和健康。降低毒性的策略包括铅笔束扫描（PBS）质子治疗（PT）。本研究旨在报告 PBS 治疗的 CBT 患者的临床结果和 QoL。
我们回顾性分析了 221 例接受 PBS 治疗的年龄<18 岁的 CBT 患者。使用 Kaplan-Meier 估计计算总生存期（OS）、无疾病生存期（DFS）和晚期毒性无生存期（TFS）、局部控制（LC）和远处（DC）脑/脊髓控制的情况。对 206 例患者（仅<4 岁的代理，患者和代理≥5 岁）前瞻性 QoL 报告进行了描述性分析。中位随访时间为 51 个月（范围为 4-222）。
诊断时的中位年龄为 3.1 岁（范围为 0.3-17.7）。主要组织学类型为室管膜瘤（n=88；39.8%）、神经胶质瘤（n=37；16.7%）、颅咽管瘤（n=22；10.0%）、非典型畸胎瘤/横纹肌样瘤（ATRT）（n=21；9.5%）和髓母细胞瘤（n=15；6.8%）。160 例（72.4%）患者接受了化疗。中位 PT 剂量为 54 Gy（相对生物效应）（范围为 18.0-64.8）。5 年 OS、DFS、LC 和 DC（95%CI）分别为 79.9%（74-85.8）、65.2%（59.8-70.6）、72.1%（65.4-78.8）和 81.8%（76.3-87.3）。19 例（8.6%）患者发生晚期 PT 相关≥G3 毒性。5 年≥G3 TFS 为 91.0%（86.3-95.7）。观察到 3 例（1.4%）继发性恶性肿瘤。PT 时年龄≤3 岁的患者（P=0.044）或接受化疗的患者（P=0.043）经历了更多的≥G3 毒性。ATRT 组织学独立预测远处脑失败（P=0.046）和死亡（P=0.01）。年龄≥5 岁的患者自我报告的 QoL 高于其父母（代理评估）。两组患者在 PT 后比基线时的社会功能和认知能力均下降，但长期整体健康状况接近正常。≤4 岁的儿童在 PT 前后的 QoL 均明显低于正常水平。
CBT 经 PBS 治疗后疗效极佳。少数患者发生晚期≥G3 毒性。年龄<5 岁的患者 QoL 和毒性结果更差。
