PDF(Pubmed)
Abstract：
OBJECTIVE: Rare but severe toxicities of the optic apparatus have been observed after treatment of intracranial tumours with proton therapy. Some adverse events have occurred at unusually low dose levels and are thus difficult to understand considering dose metrics only. When transitioning from double scattering to pencil beam scanning, little consideration was given to increased dose rates observed with the latter delivery paradigm. We explored if dose rate related metrics could provide additional predicting factors for the development of late visual toxicities.
METHODS: Radiation-induced intracranial visual pathway lesions were delineated on MRI for all index cases. Voxel-wise maximum dose rate (MDR) was calculated for 2 patients with observed optic nerve toxicities (CTCAE grade 3 and 4), and 6 similar control cases. Additionally, linear energy transfer (LET) related dose enhancing metrics were investigated.
RESULTS: For the index cases, which developed toxicities at low dose levels (mean, 50 GyRBE), some dose was delivered at higher instantaneous dose rates. While optic structures of non-toxicity cases were exposed to dose rates of up to 1 to 3.2 GyRBE/s, the pre-chiasmatic optic nerves of the 2 toxicity cases were exposed to dose rates above 3.7 GyRBE/s. LET-related metrics were not substantially different between the index and non-toxicity cases.
CONCLUSIONS: Our observations reveal large variations in instantaneous dose rates experienced by different volumes within our patient cohort, even when considering the same indications and beam arrangement. High dose rate regions are spatially overlapping with the radiation induced toxicity areas in the follow up images. At this point, it is not feasible to establish causality between exposure to high dose rates and the development of late optic apparatus toxicities due to the low incidence of injury.
METHODS: Radiation-induced intracranial visual pathway lesions were delineated on MRI for all index cases. Voxel-wise maximum dose rate (MDR) was calculated for 2 patients with observed optic nerve toxicities (CTCAE grade 3 and 4), and 6 similar control cases. Additionally, linear energy transfer (LET) related dose enhancing metrics were investigated.
RESULTS: For the index cases, which developed toxicities at low dose levels (mean, 50 GyRBE), some dose was delivered at higher instantaneous dose rates. While optic structures of non-toxicity cases were exposed to dose rates of up to 1 to 3.2 GyRBE/s, the pre-chiasmatic optic nerves of the 2 toxicity cases were exposed to dose rates above 3.7 GyRBE/s. LET-related metrics were not substantially different between the index and non-toxicity cases.
CONCLUSIONS: Our observations reveal large variations in instantaneous dose rates experienced by different volumes within our patient cohort, even when considering the same indications and beam arrangement. High dose rate regions are spatially overlapping with the radiation induced toxicity areas in the follow up images. At this point, it is not feasible to establish causality between exposure to high dose rates and the development of late optic apparatus toxicities due to the low incidence of injury.
摘要：
目的：在用质子治疗颅内肿瘤后，观察到了罕见但严重的光学装置毒性。一些不良事件发生在异常低剂量水平,因此仅考虑剂量度量难以理解。当从双散射过渡到笔形光束扫描时，很少考虑后一种给药模式观察到的剂量率增加.我们探讨了剂量率相关指标是否可以为后期视觉毒性的发展提供其他预测因素。
方法：在MRI上描绘了所有指标病例的放射性颅内视觉通路病变。计算了2例观察到的视神经毒性（CTCAE3级和4级）患者的体素最大剂量率（MDR），和6个类似的对照病例。此外,研究了与线性能量转移（LET）相关的剂量增强指标。
结果：对于索引案例，在低剂量水平下产生毒性(平均，50GyRBE),一些剂量以更高的瞬时剂量率输送。虽然无毒性病例的光学结构暴露于高达1至3.2GyRBE/s的剂量率，2例毒性病例的交叉前视神经暴露于3.7GyRBE/s以上的剂量率。LET相关指标在指数和非毒性病例之间没有实质性差异。
结论：我们的观察结果揭示了我们的患者队列中不同体积所经历的瞬时剂量率的巨大差异，即使考虑相同的指示和波束布置。在后续图像中，高剂量率区域与辐射诱导的毒性区域在空间上重叠。在这一点上,由于损伤的发生率较低，因此在高剂量率暴露与晚期光学装置毒性的发展之间建立因果关系是不可行的。
方法：在MRI上描绘了所有指标病例的放射性颅内视觉通路病变。计算了2例观察到的视神经毒性（CTCAE3级和4级）患者的体素最大剂量率（MDR），和6个类似的对照病例。此外,研究了与线性能量转移（LET）相关的剂量增强指标。
结果：对于索引案例，在低剂量水平下产生毒性(平均，50GyRBE),一些剂量以更高的瞬时剂量率输送。虽然无毒性病例的光学结构暴露于高达1至3.2GyRBE/s的剂量率，2例毒性病例的交叉前视神经暴露于3.7GyRBE/s以上的剂量率。LET相关指标在指数和非毒性病例之间没有实质性差异。
结论：我们的观察结果揭示了我们的患者队列中不同体积所经历的瞬时剂量率的巨大差异，即使考虑相同的指示和波束布置。在后续图像中，高剂量率区域与辐射诱导的毒性区域在空间上重叠。在这一点上,由于损伤的发生率较低，因此在高剂量率暴露与晚期光学装置毒性的发展之间建立因果关系是不可行的。
