Aljabab Saif, Rana Shushan, Maes Shadonna, O'Ryan-Blair Avril, Castro Jackie, Zheng Jack, Halasz Lia M, Taddei Phillip J
Radiation Oncology Department, King Saud University, Riyadh, Saudi Arabia.
Radiation Oncology Department, University of Washington School of Medicine, Seattle, WA, USA.
Int J Part Ther. 2021 Aug 2;8(3):43-54. doi: 10.14338/IJPT-21-00001.1. eCollection 2022 Winter.
Craniospinal irradiation (CSI) improves clinical outcomes at the cost of long-term neuroendocrine and cognitive sequelae. The purpose of this pilot study was to determine whether hypothalamic-pituitary axis (HPA) and hippocampus avoidance (HPA-HA) with intensity-modulated proton therapy (IMPT) can potentially reduce this morbidity compared with standard x-ray CSI.
We retrospectively evaluated 10 patients with medulloblastoma (mean, 7 years; range, 4-14 years). Target volumes and organs at risk were delineated as per our local protocol and the ACNS0331 atlas. An experienced neuroradiologist verified the HPA and hippocampus contours. The primary objective was CSI and boost clinical target volume (CTV) covering 95% of the volume (D) > 99% coverage with robustness. Described proton therapy doses in grays are prescribed using a biological effectiveness relative to photon therapy of 1.1. The combined prescribed dose in the boost target was 54 Gy. Secondary objectives included the HPA and hippocampus composite average dose (D ≤ 18 Gy). For each patient, volumetric modulated arc radiotherapy (VMAT) and tomotherapy (TOMO) plans existed previously, and a new plan was generated with 3 cranial and 1 or 2 spinal beams for pencil-beam scanning delivery. Statistical comparison was performed with 1-way analysis of variance.
Compared with standard CSI, HPA-HA CSI had statistically significant decreases in the composite doses received by the HPA (32.2 versus 17.9 Gy; < .001) and hippocampi (39.8 versus 22.8 Gy; < .001). The composite HPA D was lower in IMPT plans (17.9 Gy) compared with that of VMAT (21.8 Gy) and TOMO (21.2 Gy) plans ( = .05). Hippocampi composite D was also lower in IMPT plans (21 Gy) compared with that of VMAT (27.5 Gy) and TOMO (27.2 Gy) plans ( = .02). The IMPT CTV D coverage was lower in IMPT plans (52.8 Gy) compared with that of VMAT (54.6 Gy) and TOMO (54.6 Gy) plans ( < .001) The spared mean volume was only 1.35% (19.8 cm) of the whole-brain CTV volume (1476 cm).
We found that IMPT has the strong potential to reduce the dose to the HPA and hippocampus, compared with standard x-ray CSI while maintaining target coverage. A prospective clinical trial is required to establish the safety, efficacy, and toxicity of this novel CSI approach.
全脑脊髓照射（CSI）虽能改善临床疗效，但会带来长期神经内分泌和认知后遗症。本前瞻性研究旨在确定与标准X线CSI相比，调强质子治疗（IMPT）对下丘脑 - 垂体轴（HPA）和海马的避让（HPA - HA）是否有可能降低这种发病率。
我们回顾性评估了10例髓母细胞瘤患者（平均年龄7岁；范围4 - 14岁）。根据我们当地的方案和ACNS0331图谱勾勒靶区体积和危及器官。由一位经验丰富的神经放射科医生核实HPA和海马的轮廓。主要目标是CSI及对覆盖95%体积的临床靶区（CTV）进行推量，保证99%体积得到稳健覆盖（D）。质子治疗剂量以格雷描述，相对于光子治疗规定其生物有效性为1.1。推量靶区的联合处方剂量为54 Gy。次要目标包括HPA和海马的复合平均剂量（D≤18 Gy）。对于每位患者，之前已有容积调强弧形放疗（VMAT）和断层放疗（TOMO）计划，并生成了一个新计划，采用3个颅部和1个或2个脊髓束进行笔形束扫描照射。采用单因素方差分析进行统计学比较。
与标准CSI相比，HPA - HA CSI使HPA接受的复合剂量（32.2 Gy对17.9 Gy；P <.001）和海马接受的复合剂量（39.8 Gy对22.8 Gy；P <.001）有统计学显著降低。IMPT计划中HPA的复合D（17.9 Gy）低于VMAT（21.8 Gy）和TOMO（21.2 Gy）计划（P =.05）。IMPT计划中海马的复合D（21 Gy）也低于VMAT（27.5 Gy）和TOMO（27.2 Gy）计划（P =.02）。IMPT计划中IMPT CTV D覆盖度（52.8 Gy）低于VMAT（54.6 Gy）和TOMO（54.6 Gy）计划（P <.001）。 spared平均体积仅为全脑CTV体积（1476 cm³）的1.35%（19.8 cm³）。
我们发现，与标准X线CSI相比，IMPT在维持靶区覆盖的同时，有很大潜力降低HPA和海马的剂量。需要进行前瞻性临床试验来确定这种新型CSI方法的安全性、有效性和毒性。
