Abstract：
Objectives. (1) To examine to what extent the cell- and exposure- specific information neglected in the phenomenological proton relative biological effectiveness (RBE) models could influence the computed RBE in proton therapy. (2) To explore similarities and differences in the formalism and the results between the linear energy transfer (LET)-based phenomenological proton RBE models and the microdosimetry-based Mayo Clinic Florida microdosimetric kinetic model (MCF MKM). (3) To investigate how the relationship between the RBE and the dose-mean proton LET is affected by the proton energy spectrum and the secondary fragments.Approach. We systematically compared six selected phenomenological proton RBE models with the MCF MKM in track-segment simulations, monoenergetic proton beams in a water phantom, and two spread-out Bragg peaks. A representative comparison within vitrodata for human glioblastoma cells (U87 cell line) is also included.Main results. Marked differences were observed between the results of the phenomenological proton RBE models, as reported in previous studies. The dispersion of these models\' results was found to be comparable to the spread in the MCF MKM results obtained by varying the cell-specific parameters neglected in the phenomenological models. Furthermore, while single cell-specific correlation between RBE and the dose-mean proton LET seems reasonable above 2 keVμm-1, caution is necessary at lower LET values due to the relevant contribution of secondary fragments. The comparison within vitrodata demonstrates comparable agreement between the MCF MKM predictions and the results of the phenomenological models.Significance. The study highlights the importance of considering cell-specific characteristics and detailed radiation quality information for accurate RBE calculations in proton therapy. Furthermore, these results provide confidence in the use of the MCF MKM for clonogenic survival RBE calculations in proton therapy, offering a more mechanistic approach compared to phenomenological models.
摘要：
Objectives.（1）检查在现象学质子相对生物有效性（RBE）模型中忽略的细胞和暴露特异性信息在多大程度上影响质子治疗中的计算RBE。（2）探讨基于线性能量转移（LET）的现象学质子RBE模型与基于微剂量学的梅奥诊所佛罗里达微剂量学动力学模型（MCFMKM）之间的形式主义和结果的异同。(3)研究RBE和剂量平均质子LET之间的关系如何受到质子能谱和次级碎片的影响。方法。我们在轨道段模拟中系统地比较了六个选定的现象学质子RBE模型与MCFMKM，水中的单能质子束，和两个展开的布拉格峰。还包括人胶质母细胞瘤细胞(U87细胞系)的体外数据内的代表性比较。主要结果。在现象学质子RBE模型的结果之间观察到明显的差异，正如以前的研究报道的那样。发现这些模型结果的分散与通过改变现象学模型中忽略的细胞特异性参数而获得的MCFMKM结果的分散相当。此外，虽然RBE与剂量平均质子LET之间的单细胞特异性相关性在2keVμm-1以上似乎是合理的，但由于次级片段的相关贡献，在较低的LET值下需要谨慎。体外数据中的比较表明，MCFMKM预测与现象学模型的结果之间具有可比性。意义。该研究强调了在质子治疗中考虑细胞特异性特征和详细辐射质量信息以进行准确RBE计算的重要性。此外，这些结果为在质子治疗中使用MCFMKM进行克隆生存RBE计算提供了信心，与现象学模型相比，提供了一种更机械的方法。
