Manem Venkata S K, Kohandel Mohammad, Hodgson David C, Sharpe Michael B, Sivaloganathan Siv
Department of Applied Mathematics, University of Waterloo , Waterloo, Ontario , Canada.
Int J Radiat Biol. 2015 Mar;91(3):209-17. doi: 10.3109/09553002.2014.980466. Epub 2015 Jan 24.
Abstract Purpose: Numerous studies have implicated elevated second cancer risks as a result of radiation therapy. Our aim in this paper was to contribute to an understanding of the effects of radiation quality on second cancer risks. In particular, we developed a biologically motivated model to study the effects of linear energy transfer (LET) of charged particles (including protons, alpha particles and heavy ions Carbon and Neon) on the risk of second cancer.
A widely used approach to estimate the risk uses the so-called initiation-inactivation-repopulation model. Based on the available experimental data for the LET dependence of radiobiological parameters and mutation rate, we generalized this formulation to include the effects of radiation quality. We evaluated the secondary cancer risks for protons in the clinical range of LET, i.e., around 4-10 (KeV/μm), which lies in the plateau region of the Bragg peak.
For protons, at a fixed radiation dose, we showed that the increase in second cancer risks correlated directly with increasing values of LET to a certain point, and then decreased. Interestingly, we obtained a higher risk for proton LET of 10 KeV/μm compared to the lower LET of 4 KeV/μm in the low dose region. In the case of heavy ions, the risk was higher for Carbon ions than Neon ions (even though they have almost the same LET). We also compared protons and alpha particles with the same LET, and it was interesting to note that the second cancer risks were higher for protons compared to alpha particles in the low-dose region.
Overall, this study demonstrated the importance of including LET dependence in the estimation of second cancer risk. Our theoretical risk predictions were noticeably high; however, the biological end points should be tested experimentally for multiple treatment fields and to improve theoretical predictions.
摘要目的:众多研究表明放射治疗会导致二次癌症风险升高。本文的目的是促进对辐射质量对二次癌症风险影响的理解。具体而言,我们开发了一个基于生物学原理的模型,以研究带电粒子(包括质子、α粒子以及重离子碳和氖)的线能量转移(LET)对二次癌症风险的影响。
一种广泛用于估计风险的方法是使用所谓的启动 - 失活 - 再增殖模型。基于现有的关于放射生物学参数和突变率的LET依赖性的实验数据,我们对该公式进行了推广,以纳入辐射质量的影响。我们评估了临床LET范围内质子的二次癌症风险,即约4 - 10(keV/μm),这处于布拉格峰的平台区域。
对于质子,在固定辐射剂量下,我们表明二次癌症风险的增加与LET值的增加直接相关,直至某一点,然后下降。有趣的是,在低剂量区域,与4 keV/μm的较低LET相比,我们发现质子LET为10 keV/μm时风险更高。在重离子的情况下,碳离子的风险高于氖离子(尽管它们的LET几乎相同)。我们还比较了具有相同LET的质子和α粒子,值得注意的是,在低剂量区域,质子的二次癌症风险高于α粒子。
总体而言,本研究证明了在估计二次癌症风险时纳入LET依赖性的重要性。我们的理论风险预测明显偏高;然而,生物终点应在多个治疗领域进行实验测试,以改进理论预测。