Department of Radiation Oncology, Eastern Virginia Medical School, Norfolk, Virginia 23507, USA.
Radiat Res. 2013 Jan;179(1):21-8. doi: 10.1667/RR2737.1. Epub 2012 Nov 13.
Considerable evidence now exists to show that that the relative biological effectiveness (RBE) changes considerably along the proton depth-dose distribution, with progressively higher RBE values at the distal part of the modulated, or spread out Bragg peak (SOBP) and in the distal dose fall-off (DDF). However, the highly variable nature of the existing studies (with regards to cell lines, and to the physical properties and dosimetry of the various proton beams) precludes any consensus regarding the RBE weighting factor at any position in the depth-dose profile. We have thus conducted a systematic study on the variation in RBE for cell killing for two clinical modulated proton beams at Indiana University and have determined the relationship between the RBE and the dose-averaged linear energy transfer (LETd) of the protons at various positions along the depth-dose profiles. Clonogenic assays were performed on human Hep2 laryngeal cancer cells and V79 cells at various positions along the SOBPs of beams with incident energies of 87 and 200 MeV. There was a marked variation in the radiosensitivity of both cell lines along the SOBP depth-dose profile of the 87 MeV proton beam. Using Hep2 cells, the D(0.1) isoeffect dose RBE values (normalized against (60)Co) were 1.46 at the middle of SOBP, 2.1 at the distal end of the SOBP and 2.3 in the DDF. For V79 cells, the D(0.1) isoeffect RBE for the 87 MEV beam were 1.23 for the proximal end of the SOBP: 1.46 for the distal SOBP and 1.78 for the DDF. Similar D(0.1) isoeffect RBE values were found for Hep2 cells irradiated at various positions along the depth-dose profile of the 200 MeV beam. Our experimentally derived RBE values were significantly correlated (P = 0.001) with the mean LETd of the protons at the various depths, which confirmed that proton RBE is highly dependent on LETd. These in vitro data suggest that the RBE of the proton beam at certain depths is greater than 1.1, a value currently used in most treatment planning algorithms. Thus, the potential for increased cell killing and normal tissue damage in the distal regions of the proton SOBP may be greater than originally thought.
现在有相当多的证据表明，质子深度剂量分布中的相对生物效应（RBE）变化相当大，在调制或扩展布拉格峰（SOBP）的远端部分和在远端剂量下降（DDF）处具有逐渐更高的 RBE 值。然而，由于细胞系以及各种质子束的物理性质和剂量学方面存在的高度可变性质，使得任何关于深度剂量分布中任何位置的 RBE 加权因子的共识都无法达成。因此，我们在印第安纳大学对两种临床调制质子束的细胞杀伤 RBE 进行了系统研究，并确定了 RBE 与沿深度剂量分布的质子的剂量平均线性能量传递（LETd）之间的关系。在两种入射能量为 87 MeV 和 200 MeV 的质子束的 SOBP 上，对人喉癌细胞 Hep2 和 V79 细胞进行了集落形成试验。在 87 MeV 质子束的 SOBP 深度剂量分布上，两种细胞系的放射敏感性都有明显变化。使用 Hep2 细胞，与（60）Co 相比，归一化的 D（0.1）等效应剂量 RBE 值在 SOBP 中部为 1.46，在 SOBP 远端为 2.1，在 DDF 中为 2.3。对于 V79 细胞，87 MeV 束的 D（0.1）等效应 RBE 值在 SOBP 近端为 1.23，在 SOBP 远端为 1.46，在 DDF 中为 1.78。在 200 MeV 束的深度剂量分布上，在各个位置照射的 Hep2 细胞也得到了类似的 D（0.1）等效应 RBE 值。我们从实验中得出的 RBE 值与各深度质子的平均 LETd 显著相关（P = 0.001），这证实了质子 RBE 高度依赖于 LETd。这些体外数据表明，质子束在某些深度的 RBE 值大于 1.1，这是目前大多数治疗计划算法中使用的值。因此，质子 SOBP 远端区域的细胞杀伤和正常组织损伤的潜在风险可能比最初想象的要大。
