Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Department of Medical Physics and Biomedical Engineering, University College London, London, UK.
Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
Int J Radiat Oncol Biol Phys. 2018 Jul 15;101(4):809-819. doi: 10.1016/j.ijrobp.2018.03.037. Epub 2018 Apr 17.
Clinical practice assumes a fixed proton relative biological effectiveness (RBE) of 1.1, but in vitro experiments demonstrate higher RBEs at the distal edge of the proton spread-out Bragg peak, that is, in a region that falls within the lung for chest-wall patients. We performed retrospective qualitative and quantitative analyses of lung-density changes-indicative of asymptomatic fibrosis-for chest-wall patients treated with protons or photons. Our null hypothesis was that, assuming a fixed RBE of 1.1, these changes would be the same for the 2 cohorts, supporting current RBE practice. Our alternative hypothesis was that radiographic abnormalities would be greater for the proton cohort, suggesting an RBE > 1.1.
We analyzed follow-up computed tomography (CT) scans for 20 proton and photon patients. All were prescribed 50.4 Gy (RBE) in 28 fractions, assuming a fixed RBE of 1.1 for protons and 1 for photons. Deformable registrations enabled us to calculate density changes in the normal lung, specifically (1) median Hounsfield unit (HU) values among posttreatment CT scans and (2) changes in median HU values between pretreatment and posttreatment CT scans, both as a function of grays (RBE). In addition, qualitative abnormality grading was performed by a radiologist.
Proton patients exhibited higher values of HU/Gy (RBE) (endpoint 1) and ΔHU/Gy (RBE) (endpoint 2): P = .049 and P = .00019, respectively, were obtained (likelihood ratio tests of full linear mixed-effects models against models without "modality"). Furthermore, qualitative radiologic scoring indicated a significant difference between the cohorts (Wilcoxon P = .018; median score, 3 of 9 for protons and 1.5 of 9 for photons).
Our data support the hypothesis that the proton RBE for lung-density changes exceeds 1.1. This RBE elevation could be attributable to (1) the late, normal tissue endpoint that we consider or (2) end-of-range proton linear energy transfer elevation-or a combination of the two. Regardless, our results suggest that variations in proton RBE prove important in vivo as well as in vitro.
临床实践假设质子相对生物学效应（RBE）为 1.1，但体外实验表明在质子扩展布拉格峰的远端边缘存在更高的 RBE，即在胸部壁患者的肺部范围内。我们对接受质子或光子治疗的胸部壁患者的肺密度变化（无症状纤维化的指标）进行了回顾性定性和定量分析。我们的零假设是，假设 RBE 为 1.1 不变，这两个队列的变化将相同，支持当前的 RBE 实践。我们的替代假设是，对于质子队列，放射性异常会更大，表明 RBE>1.1。
我们分析了 20 名质子和光子患者的随访 CT 扫描。所有患者均接受了 50.4Gy（RBE）的治疗，分为 28 个分次，假设质子的固定 RBE 为 1.1，光子的 RBE 为 1。变形配准使我们能够计算正常肺中的密度变化，具体为（1）治疗后 CT 扫描中中位数的 Hounsfield 单位（HU）值，以及（2）治疗前和治疗后 CT 扫描之间中位数 HU 值的变化，均为灰度（RBE）的函数。此外，还由放射科医生进行了定性异常分级。
质子患者表现出更高的 HU/Gy（RBE）（终点 1）和ΔHU/Gy（RBE）（终点 2）值：P=0.049 和 P=0.00019（对全线性混合效应模型的似然比检验，对不包含“模态”的模型）。此外，两组之间的定性放射学评分存在显著差异（Wilcoxon P=0.018；中位数评分，质子为 9 分中的 3 分，光子为 9 分中的 1.5 分）。
我们的数据支持质子对肺密度变化的 RBE 超过 1.1 的假设。这种 RBE 升高可能归因于（1）我们考虑的晚期正常组织终点，或（2）质子线性能量传递末端升高，或两者的组合。无论如何，我们的结果表明，质子 RBE 的变化在体内和体外都很重要。
