Aims

Proton beam therapy (PBT) has increasingly been applied for the treatment of young children when radiotherapy is needed. The treatment requires intensive multimodality care and is logistically demanding. In this analysis, we evaluated our experiences in treating infants with tumours of the central nervous system with PBT.

Materials and methods

Children younger than 2 years of age treated with PBT for central nervous system tumours enrolled in the prospective registry study KiProReg were retrospectively analysed. Information on patient characteristics, treatment, toxicities and outcome were evaluated. Adverse events were classified according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE V4.0) before, during and after PBT.

Results

Between September 2013 and June 2018, 51 infants were eligible. The median age was 19 months (range 11–23 months) at the time of PBT. Tumour entities were ependymoma (51.0%), atypical teratoid rhabdoid tumour (39.0%), high-grade glioma (6.0%), pineoblastoma (2.0%) and medulloblastoma (2.0%). The prescribed median total dose was 54.0 Gy (range 45.0–59.4 Gy). Most received local radiotherapy. In four patients, craniospinal irradiation followed by a boost to the local tumour bed was applied. The median follow-up time was 42.0 months (range 7.3–86.2 months). The estimated 3-year local control, progression-free survival and overall survival rates for all patients were 62.7, 47.1 and 76.5%, respectively. During radiotherapy, 24 events of higher-grade (CTCAE ≥ °III) toxicities were reported. Interruption of radiotherapy for more than 2 days was due to infection (n = 3) or shunt complication (n = 2). Unexpected hospitalisation during radiotherapy affected 12 patients. Late adverse events attributable to radiotherapy included endocrinopathy (CTCAE °II; 7.8%), new onset of hearing loss (CTCAE °III; 5.8%) and visual impairment (CTCAE °IV; 1.9%). Transient radiation-induced imaging changes occurred in five patients (9.8%).

Conclusions

Our study indicates that PBT is feasible for very young children with central nervous system tumours, at least in the short term. However, it requires challenging interdisciplinary medical care and high logistical effort. For evaluation of late effects, longer follow-up and evaluation of neurocognitive outcome are desirable. More data have to be gathered to further define the role of radiotherapy in infants over time.

中文翻译：

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质子束治疗婴儿脑肿瘤的可行性：来自前瞻性 KiProReg 注册研究的经验

宗旨

当需要放射治疗时，质子束疗法 (PBT) 越来越多地应用于治疗幼儿。治疗需要密集的多模式护理，并且在后勤方面要求很高。在这项分析中，我们评估了我们用 PBT 治疗患有中枢神经系统肿瘤的婴儿的经验。

材料和方法

对参加前瞻性注册研究 KiProReg 的中枢神经系统肿瘤接受 PBT 治疗的 2 岁以下儿童进行了回顾性分析。评估了有关患者特征、治疗、毒性和结果的信息。根据美国国家癌症研究所不良事件通用术语标准 (CTCAE V4.0) 在 PBT 之前、期间和之后对不良事件进行分类。

结果

2013 年 9 月至 2018 年 6 月期间，51 名婴儿符合条件。PBT 时的中位年龄为 19 个月（范围 11-23 个月）。肿瘤实体为室管膜瘤 (51.0%)、非典型畸胎瘤横纹肌样瘤 (39.0%)、高级别胶质瘤 (6.0%)、松果体母细胞瘤 (2.0%) 和成神经管细胞瘤 (2.0%)。规定的中位总剂量为 54.0 Gy（范围 45.0-59.4 Gy）。大多数接受局部放疗。在四名患者中，应用了颅脊髓照射，然后对局部肿瘤床进行了加强。中位随访时间为 42.0 个月（范围 7.3-86.2 个月）。所有患者的估计 3 年局部控制率、无进展生存率和总生存率分别为 62.7%、47.1% 和 76.5%。在放疗期间，报告了 24 起更高级别（CTCAE ≥ °III）毒性事件。n = 3) 或分流并发症 ( n = 2)。放疗期间意外住院影响了 12 名患者。可归因于放疗的晚期不良事件包括内分泌病（CTCAE °II；7.8%）、新发听力损失（CTCAE °III；5.8%）和视力障碍（CTCAE °IV；1.9%）。5 名患者 (9.8%) 发生了瞬态辐射引起的成像变化。

结论

我们的研究表明，至少在短期内，PBT 对于患有中枢神经系统肿瘤的幼儿是可行的。然而，它需要具有挑战性的跨学科医疗保健和高后勤工作。对于迟发效应的评估，需要更长时间的随访和神经认知结果的评估。必须收集更多数据以进一步确定放射治疗在婴儿中的作用。