Université Paris-Saclay, CNRS/IN2P3, IJCLab, Orsay, France.
Université de Paris, IJCLab, Orsay, France.
Med Phys. 2023 Jan;50(1):570-581. doi: 10.1002/mp.15945. Epub 2022 Sep 19.
Empirical data in proton therapy indicate that relative biological effectiveness (RBE) is not constant, and it is directly related to the linear energy transfer (LET). The experimental assessment of LET with high resolution would be a powerful tool for minimizing the LET hot spots in intensity-modulated proton therapy, RBE- or LET-guided evaluation and optimization to achieve biologically optimized proton plans, verifying the theoretical predictions of variable proton RBE models, and so on. This could impact clinical outcomes by reducing toxicities in organs at risk.
The present work shows the first 2D LET maps obtained at a proton therapy facility using the double scattering delivery mode in clinical conditions by means of new silicon 3D-cylindrical microdetectors.
The device consists of a matrix of 121 independent silicon-based detectors that have 3D-cylindrical electrodes of 25-µm diameter and 20-µm depth, resulting each one of them in a well-defined micrometric radiation sensitive volume etched inside the silicon. They have been specifically designed for a hadron therapy, improving the performance of current silicon-based microdosimeters. Microdosimetry spectra were obtained at different positions of the Bragg curve by using a water-equivalent phantom along an 89-MeV pristine proton beam generated in the Y1 proton passive scattering beamline of the Orsay Proton Therapy Centre (Institut Curie, France).
Microdosimetry 2D-maps showing the variation of the lineal energy with depth in the three dimensions were obtained in situ during irradiation at clinical fluence rates (∼10 s cm ) for the first time with a spatial resolution of 200 µm, the highest achieved in the transverse plane so far. The experimental results were cross-checked with Monte Carlo simulations and a good agreement between the spectra shapes was found. The experimental frequency-mean lineal energy values in silicon were 1.858 ± 0.019 keV µm at the entrance, 2.61 ± 0.03 keV µm at the proximal distance, 4.97 ± 0.05 keV µm close to the Bragg peak, and 8.6 ± 0.1 keV µm at the distal edge. They are in good agreement with the expected trends in the literature in clinical proton beams.
We present the first 2D microdosimetry maps obtained in situ during irradiation at clinical fluence rates in proton therapy. Our results show that the arrays of 3D-cylindrical microdetectors are a reliable microdosimeter to evaluate LET maps not only in the longitudinal axis of the beam, but also in the transverse plane allowing for LET characterization in three dimensions. This work is a proof of principle showing the capacity of our system to deliver LET 2D maps. This kind of experimental data is needed to validate variable proton RBE models and to optimize LET-guided plans.
质子治疗的实证数据表明,相对生物效应(RBE)并非恒定不变,而是与线性能量传递(LET)直接相关。利用高分辨率评估 LET 将成为一种强大的工具,可用于最大限度地减少调强质子治疗中的 LET 热点、实现 RBE 或 LET 引导的评估和优化以达到生物学优化的质子计划、验证可变质子 RBE 模型的理论预测等。这可以通过降低危及器官的毒性来改善临床结果。
本研究通过使用新的硅 3D 圆柱形微探测器,在临床条件下,首次展示了在质子治疗设施中使用双散射输送模式获得的二维 LET 图谱。
该设备由 121 个独立的硅基探测器组成,这些探测器具有 25-µm 直径和 20-µm 深度的 3D 圆柱形电极,每个探测器在硅内部都有一个明确界定的微辐射敏感体积。它们专门用于强子治疗,提高了当前硅基微剂量计的性能。通过在奥赛质子治疗中心(法国居里研究所)的 Y1 质子被动散射束线中生成的 89-MeV 原始质子束,在布拉格曲线的不同位置使用水当量幻像,获得了微剂量学谱。
首次在临床通量率(约 10 s cm )下,在原位获得了具有 200 µm 空间分辨率的三维中随深度变化的线性能量微剂量学 2D 图谱,这是目前在横截面上实现的最高分辨率。实验结果与蒙特卡罗模拟进行了交叉检查,发现谱形之间存在良好的一致性。在硅中,实验频率平均线性能量值在入口处为 1.858 ± 0.019 keV µm,在近端距离处为 2.61 ± 0.03 keV µm,在布拉格峰附近为 4.97 ± 0.05 keV µm,在远端边缘处为 8.6 ± 0.1 keV µm。它们与临床质子束中文献中预期的趋势一致。
我们展示了在质子治疗的临床通量率下,首次在原位获得的二维微剂量学图谱。我们的结果表明,3D 圆柱形微探测器阵列不仅是评估束轴纵向 LET 图谱的可靠微剂量计,而且还可以在横截面上进行评估,从而实现三维 LET 特性描述。这项工作是一个原理验证,展示了我们的系统提供 LET 2D 图谱的能力。这种实验数据对于验证可变质子 RBE 模型和优化 LET 引导的计划是必要的。