Paganetti Harald
a Department of Radiation Oncology , Massachusetts General Hospital & Harvard Medical School , Boston , MA , USA.
Acta Oncol. 2017 Nov;56(11):1379-1386. doi: 10.1080/0284186X.2017.1371325. Epub 2017 Sep 18.
Proton therapy uses a constant relative biological effectiveness (RBE) of 1.1. The use of variable RBE values has been suggested but is currently not feasible due to uncertainties. The impact of variable RBE has solely been studied using dosimetric indices. This work elucidates the impact of RBE variations on tumor control and normal tissue complication probabilities (TCP/NTCP).
Models to estimate TCP and NTCP were used in combination with an empirical proton RBE model. Variations in outcome as a function of linear-quadratic model parameters for cellular radiosensitivity were determined for TCP in prostate and ependymoma. In addition, NTCP analysis was done for brainstem necrosis.
Considering a variable proton RBE as a dose-modifying factor for prescription doses and dose constraints is misleading, as TCP/NTCP do not simply scale with RBE. The dependency of RBE on α/β cannot be interpreted independent of TCP/NTCP because variations in radiosensitivity affect both photon and proton treatments. Assuming interpatient variability in radiosensitivity results in lower TCP for patients with low α/β. In proton therapy, the magnitude of TCP variations is reduced due to an RBE increase as α/β decreases. The TCP in proton therapy is less affected by interpatient variability in α/β. On the other hand, patients with a lower α/β would have a lower complication probability, which is counteracted by an increase in RBE as α/β decreases. Toxicities in proton therapy would be more affected by α/β variations compared to photon therapy.
Assessment of variable RBE in proton therapy should be based on TCP and NTCP. Potential interpatient variability in radiosensitivity causes a smaller variance in TCP but a larger variance in NTCP for proton patients. The relative TCP as a function of α/β was found to be higher than the RBE, whereas the relative NTCP was lower than a calculated RBE.
质子治疗采用恒定的相对生物效应（RBE）值1.1。有人建议使用可变的RBE值，但由于存在不确定性，目前尚不切实可行。可变RBE的影响仅通过剂量学指标进行了研究。本研究阐明了RBE变化对肿瘤控制和正常组织并发症概率（TCP/NTCP）的影响。
将估计TCP和NTCP的模型与经验质子RBE模型结合使用。针对前列腺癌和室管膜瘤的TCP，确定了作为细胞放射敏感性线性二次模型参数函数的结果变化。此外，对脑干坏死进行了NTCP分析。
将可变质子RBE视为处方剂量和剂量限制的剂量修正因子会产生误导，因为TCP/NTCP并非简单地随RBE成比例变化。RBE对α/β的依赖性不能独立于TCP/NTCP进行解释，因为放射敏感性的变化会影响光子和质子治疗。假设患者间放射敏感性存在差异，会导致α/β较低的患者TCP降低。在质子治疗中，随着α/β降低，RBE增加，TCP变化幅度减小。质子治疗中的TCP受患者间α/β差异的影响较小。另一方面，α/β较低的患者并发症概率较低，但随着α/β降低，RBE增加会抵消这一影响。与光子治疗相比，质子治疗中的毒性受α/β变化的影响更大。
质子治疗中可变RBE的评估应基于TCP和NTCP。质子治疗患者中，潜在的患者间放射敏感性差异导致TCP的方差较小，但NTCP的方差较大。发现作为α/β函数的相对TCP高于RBE，而相对NTCP低于计算得出的RBE。
