Department of Oncology and Medical Physics, Haukeland University Hospital , Bergen , Norway.
Department of Physics and Technology, University of Bergen , Bergen , Norway.
Acta Oncol. 2019 Oct;58(10):1416-1422. doi: 10.1080/0284186X.2019.1643496. Epub 2019 Jul 31.
Children with brain tumors undergoing radiotherapy are at particular risk of radiation-induced morbidity and are therefore routinely considered for proton therapy (PT) to reduce the dose to healthy tissues. The aim of this study was to apply pediatric constraints and normal tissue complication probability (NTCP) models when evaluating the differences between PT and contemporary photon-based radiotherapy, volumetric modulated arc therapy (VMAT). Forty patients (aged 1-17 years) referred from Norwegian institutions to cranial PT abroad during 2014-2016 were selected for VMAT re-planning using the original CT sets and target volumes. The VMAT and delivered PT plans were compared by dose/volume metrics and NTCP models related to growth hormone deficiency, auditory toxicity, visual impairment, xerostomia, neurocognitive outcome and secondary brain and parotid gland cancers. The supratentorial brain, temporal lobes, hippocampi, hypothalamus, pituitary glands, cochleas, salivary glands, optic nerves and chiasm received lower mean doses from PT. Reductions in population median NTCP were significant for auditory toxicity (VMAT: 3.8%; PT: 0.3%), neurocognitive outcome (VMAT: 3.0 IQ points decline at 5 years post RT; PT: 2.5 IQ points), xerostomia (VMAT: 2.0%; PT: 0.6%), excess absolute risk of secondary cancer of the brain (VMAT: 9.2%; PT: 6.7%) and salivary glands (VMAT: 2.8%; PT:0.5%). Across all patients, 23/38 PT plans had better or comparable estimated risks for all endpoints (within ±10% of the risk relative to VMAT), whereas for 1/38 patients all estimates were better or comparable with VMAT. PT reduced the volumes of normal tissues exposed to radiation, particularly low-to-intermediate dose levels, and this was reflected in lower NTCP. Of the included endpoints, substantial reductions in population medians were seen from the delivered PT plans for auditory complications, xerostomia, and risk of secondary cancers of the brain and salivary glands.
正在接受放射治疗的脑瘤儿童特别容易受到放射性并发症的影响，因此通常会考虑采用质子治疗 (PT) 来降低健康组织的剂量。本研究旨在应用儿科限制和正常组织并发症概率 (NTCP) 模型来评估 PT 与当代光子放射治疗（容积调强弧形治疗，VMAT）之间的差异。
2014-2016 年间，从挪威各机构转诊至国外进行颅 PT 的 40 名（年龄 1-17 岁）患者，使用原始 CT 集和靶区重新规划 VMAT。通过剂量/体积指标和与生长激素缺乏、听觉毒性、视力损害、口干症、神经认知结果以及继发性脑和腮腺癌相关的 NTCP 模型比较 VMAT 和已交付的 PT 计划。PT 使幕上脑、颞叶、海马体、下丘脑、垂体、耳蜗、唾液腺、视神经和视交叉接收到的平均剂量更低。听觉毒性（VMAT：3.8%；PT：0.3%）、神经认知结果（VMAT：5 年 RT 后 3 个 IQ 点下降；PT：2.5 个 IQ 点）、口干症（VMAT：2.0%；PT：0.6%）、脑和唾液腺继发性癌症的超额绝对风险（VMAT：9.2%；PT：6.7%）的人群中位数 NTCP 降低有显著统计学意义。在所有患者中，23/38 例 PT 计划对于所有终点的估计风险更好或相当（与 VMAT 相比，风险相差在±10%范围内），而对于 1/38 例患者，所有估计值与 VMAT 相比均更好或相当。
PT 降低了暴露于辐射的正常组织的体积，尤其是低至中等剂量水平，这反映在较低的 NTCP 上。在所包括的终点中，从已交付的 PT 计划中，人群中位数在听觉并发症、口干症以及脑和唾液腺继发性癌症风险方面均有显著降低。
