Department of Physics, Ionizing Radiation Research Group (GRRI), Universitat Autònoma de Barcelona, Campus UAB, Avinguda de l'Eix Central, Edicifi C, Cerdanyola del Vallès, 08193, Barcelona, Spain.
Laboratoire d'Imagerie et Modélisation en Neurobiologie et Cancérologie (IMNC), Centre National de la Recherche Scientifique (CNRS), Campus universitaire, Bât. 440, 1er étage - 15 rue Georges Clemenceau, 91406, Orsay cedex, France.
Med Phys. 2017 Oct;44(10):5378-5383. doi: 10.1002/mp.12485. Epub 2017 Aug 22.
Spatially fractionated radiotherapy is a strategy to overcome the main limitation of radiotherapy, i.e., the restrained normal tissue tolerances. A well-known example is Grid Therapy, which is currently performed at some hospitals using megavoltage photon beams delivered by Linacs. Grid Therapy has been successfully used in the management of bulky abdominal tumors with low toxicity. The aim of this work was to evaluate whether an improvement in therapeutic index in Grid Therapy can be obtained by implementing it in a flattening filter-free (FFF) Linac. The rationale behind is that the removal of the flattening filter shifts the beam energy spectrum towards lower energies and increase the photon fluence. Lower energies result in a reduction of lateral scattering and thus, to higher peak-to-valley dose ratios (PVDR) in normal tissues. In addition, the gain in fluence might allow using smaller beams leading a more efficient exploitation of dose-volume effects, and consequently, a better normal tissue sparing.
Monte Carlo simulations were used to evaluate realistic dose distributions considering a 6 MV FFF photon beam from a standard medical Linac and a cerrobend mechanical collimator in different configurations: grid sizes of 0.3 × 0.3 cm , 0.5 × 0.5 cm , and 1 × 1 cm and a corresponding center-to-center (ctc) distance of 0.6, 1, and 2 cm, respectively (total field size of 10 × 10 cm ). As figure of merit, peak doses in depth, PVDR, output factors (OF), and penumbra values were assessed.
Dose at the entrance is slightly higher than in conventional Grid Therapy. However, it is compensated by the large PVDR obtained at the entrance, reaching a maximum of 35 for a grid size of 1 × 1 cm . Indeed, this grid size leads to very high PVDR values at all depths (≥ 10), which are much higher than in standard Grid Therapy. This may be beneficial for normal tissues but detrimental for tumor control, where a lower PVDR might be requested. In that case, higher valley doses in the tumor could be achieved by using an interlaced approach and/or adapting the ctc distance. The smallest grid size (0.3 × 0.3 cm ) leads to low PVDR at all depths, comparable to standard Grid Therapy. However, the use of very thin beams might increase the normal tissue tolerances with respect to the grid size commonly used (1 × 1 cm ). The gain in fluence provided by FFF implies that the important OF reduction (0.6) will not increase treatment time. Finally, the intermediate configuration (0.5 × 0.5 cm ) provides high PVDR in the first 5 cm, and comparable PVDR to previous Grid Therapy works at depth. Therefore, this configuration might allow increasing the normal tissue tolerances with respect to Grid Therapy thanks to the higher PVDR and thinner beams, while a similar tumor control could be expected.
The implementation of Grid Therapy in an FFF photon beam from medical Linac might lead to an improvement of the therapeutic index. Among the cases evaluated, a grid size of 0.5 × 0.5 cm (1-cm-ctc) is the most advantageous configuration from the physics point of view. Radiobiological experiments are needed to fully explore this new avenue and to confirm our results.
分次放射治疗是克服放射治疗主要限制的策略,即限制正常组织耐受量。一个众所周知的例子是网格治疗,目前一些医院使用直线加速器提供的兆伏光子束在进行网格治疗。网格治疗已成功用于治疗大体积腹部肿瘤,毒性低。本研究的目的是评估在没有滤过板的直线加速器(FFF)中实施网格治疗是否可以提高治疗指数。其背后的基本原理是,去除滤过板会使光束能谱向更低的能量转移,并增加光子通量。较低的能量会导致横向散射减少,因此在正常组织中峰谷剂量比(PVDR)更高。此外,剂量的增加可能允许使用更小的射束,从而更有效地利用剂量体积效应,从而更好地保护正常组织。
使用蒙特卡罗模拟来评估在不同配置下使用标准医用直线加速器的 6 MV FFF 光子束和 Cerrobend 机械准直器的实际剂量分布:网格尺寸分别为 0.3×0.3 cm、0.5×0.5 cm 和 1×1 cm,相应的中心到中心(ctc)距离分别为 0.6、1 和 2 cm,总射野尺寸为 10×10 cm。以峰值剂量、PVDR、输出因子(OF)和半影值为评价指标。
入口处的剂量略高于传统的网格治疗。然而,它被入口处获得的大 PVDR所补偿,最大可达 35,对于 1×1 cm 的网格尺寸。事实上,这种网格尺寸在所有深度(≥10)都能产生非常高的 PVDR 值,比标准的网格治疗高得多。这可能对正常组织有益,但对肿瘤控制不利,肿瘤控制可能需要较低的 PVDR。在这种情况下,通过使用交错方法和/或调整 ctc 距离,可以实现肿瘤内更高的谷底剂量。最小的网格尺寸(0.3×0.3 cm)在所有深度都产生较低的 PVDR,与标准的网格治疗相当。然而,使用非常薄的射束可能会增加相对于常用网格尺寸(1×1 cm)的正常组织耐受量。FFF 提供的剂量增加意味着重要的 OF 降低(0.6)不会增加治疗时间。最后,中间配置(0.5×0.5 cm)在最初的 5 cm 内提供高 PVDR,并且在深度处与以前的网格治疗工作具有可比的 PVDR。因此,与网格治疗相比,这种配置可能通过更高的 PVDR 和更薄的射束来提高正常组织的耐受量,同时可以预期类似的肿瘤控制。
在医用直线加速器的 FFF 光子束中实施网格治疗可能会提高治疗指数。在所评估的病例中,从物理角度来看,0.5×0.5 cm(1 cm-ctc)的网格尺寸是最有利的配置。需要进行放射生物学实验来充分探索这一新途径并验证我们的结果。