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采用潜在纳米颗粒剂量增强的聚焦千伏 X 射线放射治疗眼病的蒙特卡罗剂量学建模。

Monte Carlo dosimetry modeling of focused kV x-ray radiotherapy of eye diseases with potential nanoparticle dose enhancement.

机构信息

Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT, 06510, USA.

School of Biomedical Engineering, Capital Medical University, Beijing, 100069, China.

出版信息

Med Phys. 2018 Oct;45(10):4720-4733. doi: 10.1002/mp.13144. Epub 2018 Sep 21.

Abstract

PURPOSE

Eye plaque brachytherapy is the most common approach for intraocular cancer treatment. It is, however, invasive and subject to large setup uncertainty due to the surgical operation. We propose a novel-focused kV x-ray technique with potential nanoparticle (NP) enhancement and evaluate its application in treating choroidal melanoma and iris melanoma by Monte Carlo (MC) dosimetry modeling.

METHODS

A polycapillary x-ray lens was used to focus 45 kVp x rays to achieve pinpoint accuracy of dose delivery to small tumors near critical structures. In addition to allowing for beam focusing, the use of kV x rays takes advantage of the strong photoelectric absorption of metallic NPs in that energy regime and hence strong radiosensitization. We constructed an MC simulation program that takes into account the x-ray optic modeling and used GEANT4 for dosimetric calculation. Extensive phantom measurements using a prototype-focused x-ray system were carried out. The MC simulation of simple geometry phantom irradiation was first compared to measurements to verify the x-ray optic lens modeling in conjunction with the Geant4 dosimetric calculation. To simulate tumor treatment, a geometric eye model and two tumor models were constructed. Dose distributions of the simulated treatments were then calculated. NP radiosensitization was also simulated for two concentrations of 2 nm gold NP (AuNP) uniformly distributed in the tumor.

RESULTS

The MC-simulated full width at half maximum (FWHM) and central-axis depth dose of the focused kV x-ray beam match those measured on EBT3 films within ~10% around the depth of focus of the beam. Dose distributions of the simulated ocular tumor treatments show that focused x-ray beams can concentrate the high-dose region in or close to the tumor plus margin. For the simulated posterior choroidal tumor treatment, with sufficient tumor coverage, the doses to the optic disc and fovea are substantially reduced with focused x-ray therapy compared to eye plaque treatment (3.8 vs 39.8 Gy and 11.1 vs 53.8 Gy, respectively). The eye plaque treatment was calculated using an Eye Physics plaque with I-125 seeds under TG43 assumption. For the energy spectrum used in this study, the average simulated dose enhancement ratios (DERs) are roughly 2.1 and 1.1 for 1.0% and 0.1% AuNP mass concentration in the tumor, respectively.

CONCLUSION

Compared to eye plaque brachytherapy, the proposed focused kV x-ray technique is noninvasive and shows great advantage in sparing healthy critical organs without sacrificing the tumor control. The NP radiation dose enhancement is considerable at our proposed kV range even with a low NP concentration in the tumor, providing better critical structure protection and more flexibility for treatment planning.

摘要

目的

眼部敷贴近距离放射治疗是治疗眼内肿瘤的最常用方法。然而,由于手术的原因,它具有侵入性,并且存在较大的摆位不确定性。我们提出了一种新的聚焦千伏 X 射线技术,具有潜在的纳米粒子(NP)增强作用,并通过蒙特卡罗(MC)剂量学建模评估其在治疗脉络膜黑色素瘤和虹膜黑色素瘤中的应用。

方法

使用多毛细管 X 射线透镜将 45 kVp X 射线聚焦,以实现对靠近关键结构的小肿瘤的精确剂量输送。除了允许聚焦光束外,使用千伏 X 射线还利用了在该能量范围内金属 NP 的强光电吸收特性,从而实现了强烈的放射增敏作用。我们构建了一个 MC 模拟程序,该程序考虑了 X 射线光学建模,并使用 GEANT4 进行剂量计算。使用原型聚焦 X 射线系统进行了广泛的体模测量。首先将简单几何体模照射的 MC 模拟与测量结果进行比较,以验证 X 射线光学透镜建模与 Geant4 剂量计算的结合。为了模拟肿瘤治疗,构建了一个几何眼模型和两个肿瘤模型。然后计算模拟治疗的剂量分布。还模拟了两种浓度的 2nm 金纳米粒子(AuNP)均匀分布在肿瘤中的 NP 放射增敏作用。

结果

MC 模拟的聚焦千伏 X 射线束的半高全宽(FWHM)和中心轴深度剂量与束的焦深周围 10%范围内 EBT3 胶片上测量的结果相匹配。模拟眼肿瘤治疗的剂量分布表明,聚焦 X 射线束可以将高剂量区域集中在肿瘤加边缘内或附近。对于模拟的后部脉络膜肿瘤治疗,如果有足够的肿瘤覆盖,与眼贴治疗相比,聚焦 X 射线治疗可大大降低视盘和黄斑的剂量(分别为 3.8Gy 和 39.8Gy,11.1Gy 和 53.8Gy)。眼贴治疗是在 TG43 假设下使用带有 I-125 种子的 Eye Physics 眼贴进行计算的。对于本研究中使用的能谱,在肿瘤中 1.0%和 0.1%AuNP 质量浓度下,平均模拟剂量增强比(DER)分别约为 2.1 和 1.1。

结论

与眼贴近距离放射治疗相比,所提出的聚焦千伏 X 射线技术是非侵入性的,在不牺牲肿瘤控制的情况下,对保护健康的关键器官具有很大的优势。即使在肿瘤中 NP 浓度较低的情况下,在我们提出的千伏范围内,NP 辐射剂量增强也相当可观,为关键结构保护提供了更好的保护,并为治疗计划提供了更大的灵活性。

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