Paganetti H, Olko P, Kobus H, Becker R, Schmitz T, Waligorski M P, Filges D, Müller-Gärtner H W
Institute of Medicine IME, Forschungszentrum Jülich GmbH, Germany.
Int J Radiat Oncol Biol Phys. 1997 Feb 1;37(3):719-29. doi: 10.1016/s0360-3016(96)00540-8.
The microdosimetric weighting function approach is used widely for beam comparison studies. The suitability of this model to predict the relative biological effectiveness (RBE) of therapeutic proton beams was studied. The RBE(alpha) (i.e., linear approximation) dependence on the type of biological end point, initial proton energy, energy spread of the input proton beam, and depth of beam penetration was investigated.
Proton transport calculations for a proton energy range from 70 to 250 MeV were performed to obtain proton energy spectra at a given depth. The corresponding microdosimetric distributions of lineal energy were calculated. To these distributions the biological response function approach was applied to calculate RBE(alpha) the biological effectiveness based on a linear dose-response relationship. The early intestinal tolerance assessed by crypt regeneration in mice and the inactivation of V79 cells were taken as biological end points.
The RBE(alpha) values approach about 1 in the plateau region and gradually increase with the proton penetration depth. In the center of the Bragg peak, at the maximum dose delivery, the values of RBE(alpha) range from 1.1 (250-MeV beam, early intestinal tolerance in mice) to 1.9 (70-MeV beam, Chinese hamster V79 cells in G1/S phase). Distal to the Bragg peak, where only a small fraction of dose is delivered, the RBE(alpha) was found to be even higher. For modulated proton beams we found an increasing RBE(alpha) with depth in the spread-out Bragg peak (SOBP). Values up to 1.37 at the distal end of the SOBP plateau (155-MeV beam, SOBP between 5.3 and 13.2 cm) were obtained.
More experimental work on the determination of microdosimetric weighting functions is needed. The results of the presented calculations indicate that for therapy planning it may be necessary to account for a depth dependence on proton RBE, especially for lower energy.
微剂量加权函数方法广泛用于射束比较研究。本研究探讨了该模型预测治疗性质子束相对生物效应（RBE）的适用性。研究了RBE(α)（即线性近似）对生物终点类型、初始质子能量、输入质子束的能量展宽以及束流穿透深度的依赖性。
对70至250 MeV的质子能量范围进行质子输运计算，以获得给定深度处的质子能谱。计算了相应的线性能量微剂量分布。对这些分布应用生物响应函数方法，基于线性剂量反应关系计算RBE(α)即生物效应。以小鼠隐窝再生评估的早期肠道耐受性和V79细胞失活作为生物终点。
RBE(α)值在坪区接近1，并随着质子穿透深度逐渐增加。在布拉格峰中心，即最大剂量传递处，RBE(α)值范围为1.1（250 MeV束流，小鼠早期肠道耐受性）至1.9（70 MeV束流，处于G1/S期的中国仓鼠V79细胞）。在布拉格峰远端，此处仅传递一小部分剂量，发现RBE(α)甚至更高。对于调制质子束，我们发现在扩展布拉格峰（SOBP）中RBE(α)随深度增加。在SOBP坪区远端（155 MeV束流，SOBP在5.3至13.2 cm之间）获得的值高达1.37。
需要开展更多关于确定微剂量加权函数的实验工作。本计算结果表明，对于治疗计划，可能有必要考虑质子RBE的深度依赖性，尤其是对于较低能量。
