Nuclear interactions in proton therapy: dose and relative biological effect distributions originating from primary and secondary particles
Nuclear interactions in proton therapy: dose and relative biological effect distributions originating from primary and secondary particles
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DOI：
10.1088/0031-9155/47/5/305
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发表时间：
2002-03-07
影响因子：
3.5
通讯作者：
Paganetti, H
中科院分区：
文献类型：
--
作者：
Paganetti, H
带电粒子治疗中的剂量分布是由一次粒子和二次粒子引起的。次生核起源于非弹性核相互作用，引起人们的兴趣有三个原因。首先，如果设想快速蒙特卡罗治疗计划，问题是是否所有核相互作用产品都对总剂量有重大贡献，因此需要跟踪。其次，由于低能量和/或重次级物质，可能会有增强的相对生物有效性(RBE)。从理论上研究了不同质子束能量下，不同核相互作用通道的粒子产额随质子穿透深度的变化规律。模拟了含和不含骨材料的160 MeV质子束的初级和次级粒子的三维剂量分布，以及水中3x3x3 cm(3)的扩展布拉格峰(SOBP)。在非调制质子束的布拉格峰附近，二次质子的释放量约占总剂量的10%，它们会影响SOBP的平坦度。此外，它们还由于核相互作用产生的次级粒子的前向发射而导致剂量积累。发现d、t、He-3和α粒子沉积的剂量不到总剂量的0.1%。在160-250 MeV的四种质子束能量范围内，研究了释放的中子引起的靶体远端剂量，发现对于3×3×3 cm(3)靶，其剂量低于规定靶剂量的0.05%(SOBP远端2厘米)。Bragg峰(100%剂量)附近的RBE受次级粒子(主要是质子和α粒子)的影响，具有很强的剂量依赖性，导致RBE值高达1.2(2GY；V79失活)。根据所考虑的终点，次级粒子在2Gy时会引起RBE最高8%的漂移。相反，Bragg峰的径向能量几乎完全由初级质子决定，因为次级粒子注量随深度递减。在Bragg峰远端1 cm处，RBE值最高可达1.3(2GyV79失活)。人皮肤成纤维细胞和小鼠淋巴瘤细胞的失活也被分析，并揭示了总RBE的组织依赖性。这项研究的结果表明，RBE值升高不仅发生在SOBP的远端边缘。虽然变化不大，而且在大多数情况下可能没有可观察到的临床效果，但在某些治疗情况下，可能必须考虑这些变化。使用辐射品质因数10来分析靶下游的生物效应。生物剂量被发现低于规定的目标剂量的0.5%(对于3x3x3 cm(3)SOBP)，但取决于SOBP的大小。该剂量对于晚期效应，如致癌作用，不应显著影响。
The dose distribution delivered in charged particle therapy is due to both primary and secondary particles. The secondaries, originating from nonelastic nuclear interactions, are of interest for three reasons. First, if fast Monte Carlo treatment planning is envisaged, the question arises whether all nuclear interaction products deliver a significant contribution to the total dose and, hence, need to be tracked. Second, there could be an enhanced relative biological effectiveness (RBE) due to low energy and/or heavy secondaries. Third, neutrons originating from nuclear interactions may deliver dose outside the target volume.The particle yield from different nuclear interaction channels as a function of proton penetration depth was studied theoretically for different proton beam energies. Three-dimensional dose distributions from primary and secondary particles were simulated for an unmodulated 160 MeV proton beam with and without including a slice of bone material and for a spread-out Bragg peak (SOBP) of 3 x 3 x 3 cm(3) in water. Secondary protons deliver up to approximate to10% of the total dose proximal to the Bragg peak of an unmodulated proton beam and they affect the flatness of the SOBP. Furthermore, they cause a dose build-up due to forward emission of secondary particles from nuclear interactions. The dose deposited by d, t, He-3 and alpha-particles was found to contribute less than 0.1% of the total dose. The dose distal to the target volume caused by liberated neutrons was studied for four proton beam energies in the range of 160-250 MeV and found to be below 0.05% (2 cm distal to SOBP) of the prescribed target dose for a 3 x 3 x 3 cm(3) target.RBE values relative to Co-60 were calculated proximal to and within the SOBP. The RBE proximal to the Bragg peak (100% dose) is influenced by secondary particles (mainly protons and alpha-particles) with a strong dose dependency resulting in RBE values up to 1.2 (2 Gy; inactivation of V79). Depending, on the endpoint considered, secondary particles cause a shift in RBE by up to 8% at 2 Gy. In contrast, the RBE in the Bragg peak is almost entirely determined by primary protons due to a decreasing secondary particle fluence with depth. RBE values up to 1.3 (2 Gy; inactivation of V79) at I cm distal to the Bragg peak maximum were found. The inactivations of human skin fibroblasts and mouse lymphoma cells were also analysed and reveal a substantial tissue dependency of the total RBE. The outcome of this study shows that elevated RBE values occur not only at the distal edge of the SOBP. Although the variations are modest, and in most cases might have no observable clinical effect, they might have to be considered in certain treatment situations.The biological effect downstream of the target caused by neutrons was analysed using a radiation quality factor of 10. The biological dose was found to be below 0.5% of the prescribed target dose (for a 3 x 3 x 3 cm(3) SOBP) but depends on the size of the SOBP. This dose should not be significant with respect to late effects, e.g. cancer induction.