IMNC-UMR 8165, CNRS; Paris 11 Universities, 15 rue Georges Clemenceau, 91406, Orsay Cedex, France.
Med Phys. 2017 May;44(5):1921-1929. doi: 10.1002/mp.12175. Epub 2017 Mar 30.
Charged particles have several advantages over x-ray radiations, both in terms of physics and radiobiology. The combination of these advantages with those of minibeam radiation therapy (MBRT) could help enhancing the therapeutic index for some cancers with poor prognosis. Among the different ions explored for therapy, carbon ions are considered to provide the optimum physical and biological characteristics. Oxygen could be advantageous due to a reduced oxygen enhancement ratio along with a still moderate biological entrance dose. The aforementioned reasons justified an in-depth evaluation of the dosimetric features of carbon and oxygen minibeam radiation therapy to establish the interest of further explorations of this avenue.
The GATE/Geant4 6.2 Monte Carlo simulation platform was employed to simulate arrays of rectangular carbon and oxygen minibeams (600 μm × 2 cm) at a water phantom entrance. They were assumed to be generated by means of a magnetic focusing. The irradiations were performed with a 2-cm-long spread-out Bragg peak (SOBP) centered at 7-cm-depth. Several center-to-center (c-t-c) distances were considered. Peak and valley doses, as well as peak-to-valley dose ratio (PVDR) and the relative contribution of nuclear fragments and electromagnetic processes were assessed. In addition, the type and proportion of the secondary nuclear fragments were evaluated in both peak and valley regions.
Carbon and oxygen MBRT lead to very similar dose distributions. No significant advantage of oxygen over carbon ions was observed from physical point of view. Favorable dosimetric features were observed for both ions. Thanks to the reduced lateral scattering, the standard shape of the depth dose curves (in the peaks) is maintained even for submillimetric beam sizes. When a narrow c-t-c is considered (910-980 μm), a (quasi) homogenization of the dose can be obtained at the target, while a spatial fractionation of the dose is maintained in the proximal normal tissues with low PVDR. In contrast when a larger c-t-c is used (3500 μm) extremely high PVDR (≥ 50) are obtained in normal tissues, corresponding to very low valley doses. This suggests that carbon and oxygen MBRT might lead to a significant reduction of normal tissue complication probability. The main participant to the valley doses are secondary nuclear products at all depths. Among them the highest yield in normal tissues corresponds to the lightest fragments, neutrons and protons. Heavier fragments are dominant in the valleys only at the target position, which might favor tumor control.
The computed dose distributions suggest that a spatial fractionation of the dose combined to the use of submillimetric field sizes might allow profiting from the high efficiency of carbon and oxygen ions for the treatment of radioresistant tumors, while preserving normal tissues. Only biological experiments could confirm the shifting of the normal tissue complication probability curves. The authors' results support the further exploration of this avenue.
与 X 射线辐射相比，带电粒子在物理和放射生物学方面都具有多种优势。将这些优势与微束放射治疗（MBRT）相结合，可能有助于提高某些预后不良癌症的治疗指数。在探索用于治疗的各种离子中，碳离子被认为提供了最佳的物理和生物学特性。由于氧增强比降低以及生物学入口剂量仍适中，因此氧可能具有优势。鉴于上述原因，我们对碳和氧微束辐射治疗的剂量学特征进行了深入评估，以确定进一步探索这一途径的意义。
使用 GATE/Geant4 6.2 蒙特卡罗模拟平台模拟水模入口处的矩形碳和氧微束（600 μm×2 cm）阵列。假设它们是通过磁聚焦产生的。辐照是在 7 cm 深度的中心扩展布拉格峰（SOBP）上进行的。考虑了几个中心到中心（c-t-c）距离。评估了峰值和谷值剂量以及峰值到谷值剂量比（PVDR）和核碎片和电磁过程的相对贡献。此外，还评估了峰区和谷区的次级核碎片的类型和比例。
碳和氧 MBRT 导致非常相似的剂量分布。从物理角度来看，氧离子没有明显优于碳离子的优势。两种离子都具有良好的剂量学特征。由于横向散射减少，即使对于亚毫米束尺寸，峰值处的深度剂量曲线（标准形状）也得以保持。当考虑较窄的 c-t-c（910-980 μm）时，在靶区可以获得剂量的（准）均匀化，而在近端正常组织中保持剂量的空间分割，具有较低的 PVDR。相比之下，当使用较大的 c-t-c（3500 μm）时，在正常组织中会获得极高的 PVDR（≥50），对应的谷值剂量非常低。这表明碳和氧 MBRT 可能会显著降低正常组织并发症的概率。在所有深度处，次级核产物是谷值剂量的主要参与者。其中，在正常组织中最高的产额对应于最轻的碎片、中子和质子。较重的碎片仅在靶区处于主导地位，这可能有利于肿瘤控制。
计算出的剂量分布表明，剂量的空间分割与亚毫米场尺寸的使用相结合，可能使碳和氧离子治疗抗辐射肿瘤的高效率受益，同时保护正常组织。只有生物学实验才能证实正常组织并发症概率曲线的转移。作者的结果支持进一步探索这一途径。
