Lee Eva K, Fox Tim, Crocker Ian
Center for Operations Research in Medicine, School of Industrial and Systems Engineering, Georgia Institute of Technology, Atlanta, GA 30332-0205, USA.
Int J Radiat Oncol Biol Phys. 2006 Jan 1;64(1):301-20. doi: 10.1016/j.ijrobp.2005.08.023. Epub 2005 Nov 14.
In current intensity-modulated radiation therapy (IMRT) plan optimization, the focus is on either finding optimal beam angles (or other beam delivery parameters such as field segments, couch angles, gantry angles) or optimal beam intensities. In this article we offer a mixed integer programming (MIP) approach for simultaneously determining an optimal intensity map and optimal beam angles for IMRT delivery. Using this approach, we pursue an experimental study designed to (a) gauge differences in plan quality metrics with respect to different tumor sites and different MIP treatment planning models, and (b) test the concept of critical-normal-tissue-ring--a tissue ring of 5 mm thickness drawn around the planning target volume (PTV)--and its use for designing conformal plans.
Our treatment planning models use two classes of decision variables to capture the beam configuration and intensities simultaneously. Binary (0/1) variables are used to capture "on" or "off" or "yes" or "no" decisions for each field, and nonnegative continuous variables are used to represent intensities of beamlets. Binary and continuous variables are also used for each voxel to capture dose level and dose deviation from target bounds. Treatment planning models were designed to explicitly incorporate the following planning constraints: (a) upper/lower/mean dose-based constraints, (b) dose-volume and equivalent-uniform-dose (EUD) constraints for critical structures, (c) homogeneity constraints (underdose/overdose) for PTV, (d) coverage constraints for PTV, and (e) maximum number of beams allowed. Within this constrained solution space, five optimization strategies involving clinical objectives were analyzed: optimize total intensity to PTV, optimize total intensity and then optimize conformity, optimize total intensity and then optimize homogeneity, minimize total dose to critical structures, minimize total dose to critical structures and optimize conformity simultaneously. We emphasize that the objectives that include optimizing conformity make use of the critical-normal-tissue-ring. Three tumor sites: head-and-neck, pediatric brain, and prostate are used for comparison.
The critical-normal-tissue-ring acts as a good device for enforcing conformity. Trends in the characteristics and quality of plans resulting from each model were observed. Attempts to reduce dose to critical structures tend to worsen PTV conformity (1.542 to 3.092) and homogeneity (1.223 to 1.984), depending on the relative size and spatial distance of the critical structures to the PTV. When the critical structures are relatively small compared with the PTV (as in the case for the pediatric brain tumor, where each is less than 15% in volume), dose reduction to critical structures is accompanied by much worse scores in conformity (2.482) and homogeneity (1.984). When the critical structures are larger, as in the case of head-and-neck (approximately 50%), the conformity and homogeneity deterioration is less significant (1.542 and 1.239, respectively). There is a clear tradeoff between homogeneity, conformity, and minimum dose to organs at risk (OARs). For head-and-neck and pediatric brain tumor, the model that minimizes total dose to critical structures and optimizes conformity simultaneously offers a compromise among these factors, resulting in reduced critical structure dose with conformal and homogeneous plans. In the prostate case, the tumor is smaller than the two large nearby critical structures, and all models provide very homogeneous PTV dose distribution. However, minimizing dose to critical structures worsens conformity, as it spreads the radiation to the area surrounding the PTV. The maximum dose to the critical structures also increases slightly. Compared with plans used in the clinic which generally have uniformly spaced beam angles, the optimal clinically acceptable plans obtained via the methods herein do not have equispaced beams. The optimal beam angles returned appear to be nonintuitive, and depend on PTV size and geometry and the spatial relationship between the tumor and critical structures.
The MIP model described allows simultaneous optimization over the space of beamlet fluence weights and beam and couch angles. Based on experiments with tumor data, this approach can return good plans that are clinically acceptable and practical. This work distinguishes itself from recent IMRT research in several ways. First, in previous methods beam angles are selected before intensity map optimization. Herein, we employ 0/1 variables to model the set of candidate beams, and thereby allow the optimization process itself to select optimal beams. Second, instead of incorporating dose-volume criteria within the objective function as in previous work, herein, a combination of discrete and continuous variables associated with each voxel provides a mechanism to strictly enforce dose-volume criteria within the constraints. Third, using the construct of critical-normal-tissue-ring within the objective function can enhance the achievement of conformal plans. Based on the three tumor sites considered, it appears that volume and spatial geometry with respect to the PTV are important factors to consider when selecting objectives to optimize, and in estimating how well suited a particular model is for achieving a specified goal.
在当前的调强放射治疗(IMRT)计划优化中,重点要么是找到最佳射束角度(或其他射束传输参数,如射野分段、治疗床角度、机架角度),要么是找到最佳射束强度。在本文中,我们提供了一种混合整数规划(MIP)方法,用于同时确定IMRT传输的最佳强度图和最佳射束角度。使用这种方法,我们进行了一项实验研究,旨在(a)评估不同肿瘤部位和不同MIP治疗计划模型在计划质量指标方面的差异,以及(b)测试关键正常组织环的概念——在计划靶区(PTV)周围绘制的厚度为5mm的组织环——及其在设计适形计划中的应用。
我们的治疗计划模型使用两类决策变量来同时捕获射束配置和强度。二元(0/1)变量用于捕获每个射野的“开”或“关”或“是”或“否”决策,非负连续变量用于表示子射束的强度。二元和连续变量也用于每个体素,以捕获剂量水平和与靶区边界的剂量偏差。治疗计划模型被设计为明确纳入以下计划约束:(a)基于剂量上限/下限/平均值的约束,(b)关键结构的剂量体积和等效均匀剂量(EUD)约束,(c)PTV的均匀性约束(剂量不足/过量),(d)PTV的覆盖约束,以及(e)允许的最大射束数量。在这个受限的解空间内,分析了五种涉及临床目标的优化策略:优化PTV的总强度、优化总强度然后优化适形度、优化总强度然后优化均匀性、最小化关键结构的总剂量、最小化关键结构的总剂量并同时优化适形度。我们强调,包括优化适形度的目标利用了关键正常组织环。使用三个肿瘤部位:头颈、小儿脑和前列腺进行比较。
关键正常组织环是增强适形性的良好工具。观察到每个模型产生的计划在特征和质量方面的趋势。试图降低关键结构的剂量往往会使PTV的适形性(从1.542到3.092)和均匀性(从1.223到1.984)变差,这取决于关键结构与PTV的相对大小和空间距离。当关键结构与PTV相比相对较小时(如小儿脑肿瘤的情况,每个结构的体积小于15%),降低关键结构的剂量会伴随着适形性(2.482)和均匀性(1.984)得分更差。当关键结构较大时,如头颈的情况(约50%),适形性和均匀性的恶化不太显著(分别为1.542和1.239)。在均匀性、适形性和危及器官(OAR)的最小剂量之间存在明显的权衡。对于头颈和小儿脑肿瘤,同时最小化关键结构的总剂量并优化适形性的模型在这些因素之间提供了一种折衷,从而在适形且均匀的计划中降低了关键结构的剂量。在前列腺的情况下,肿瘤比附近的两个大关键结构小,并且所有模型都提供非常均匀的PTV剂量分布。然而,最小化关键结构的剂量会使适形性变差,因为它将辐射扩散到PTV周围的区域。关键结构的最大剂量也略有增加。与临床中通常具有均匀间隔射束角度的计划相比,通过本文方法获得的最佳临床可接受计划不具有等间隔射束。返回的最佳射束角度似乎不符合直觉,并且取决于PTV的大小和几何形状以及肿瘤与关键结构之间的空间关系。
所描述的MIP模型允许在子射束注量权重以及射束和治疗床角度的空间上进行同时优化。基于对肿瘤数据的实验,这种方法可以返回临床上可接受且实用的良好计划。这项工作在几个方面与最近的IMRT研究有所不同。首先,在以前的方法中,射束角度是在强度图优化之前选择的。在这里,我们使用0/1变量对候选射束集进行建模,从而允许优化过程本身选择最佳射束。其次,与以前的工作不同,本文不是在目标函数中纳入剂量体积标准,而是与每个体素相关联的离散和连续变量的组合提供了一种在约束内严格执行剂量体积标准的机制。第三,在目标函数中使用关键正常组织环的结构可以增强适形计划的实现。基于所考虑的三个肿瘤部位,似乎相对于PTV的体积和空间几何形状是选择优化目标以及估计特定模型实现指定目标的适合程度时要考虑的重要因素。