Witte Marnix G, Sonke Jan-Jakob, Siebers Jeffrey, Deasy Joseph O, van Herk Marcel
The Netherlands Cancer Institute, Amsterdam, Netherlands.
Phys Med Biol. 2017 Sep 20;62(19):7874-7888. doi: 10.1088/1361-6560/aa87fe.
In the past, hypothetical spherical target volumes and ideally conformal dose distributions were analyzed to establish the safety of planning target volume (PTV) margins. In this work we extended these models to estimate how alternative methods of shaping dose distributions could lead to clinical improvements. Based on a spherical clinical target volume (CTV) and Gaussian distributions of systematic and random geometrical uncertainties, idealized 3D dose distributions were optimized to exhibit specific stochastic properties. A nearby spherical organ at risk (OAR) was introduced to explore the benefit of non-spherical dose distributions. Optimizing for the same minimum dose safety criterion as implied by the generally accepted use of a PTV, the extent of the high dose region in one direction could be reduced by half provided that dose in other directions is sufficiently compensated. Further reduction of this unilateral dosimetric margin decreased the target dose confidence, however the actual minimum CTV dose at 90% confidence typically exceeded the minimum PTV dose by 20% of prescription. Incorporation of smooth dose-effect relations within the optimization led to more concentrated dose distributions compared to the use of a PTV, with an improved balance between the probability of tumor cell kill and the risk of geometrical miss, and lower dose to surrounding tissues. Tumor control rate improvements in excess of 20% were found to be common for equal integral dose, while at the same time evading a nearby OAR. These results were robust against uncertainties in dose-effect relations and target heterogeneity, and did not depend on 'shoulders' or 'horns' in the dose distributions.
过去，人们通过分析假设的球形靶区体积和理想的适形剂量分布来确定计划靶区（PTV）边界的安全性。在这项工作中，我们扩展了这些模型，以估计剂量分布塑形的替代方法如何能带来临床改善。基于球形临床靶区体积（CTV）以及系统和随机几何不确定性的高斯分布，对理想化的三维剂量分布进行优化，使其呈现特定的随机特性。引入一个附近的球形危及器官（OAR）来探索非球形剂量分布的益处。在与普遍接受的PTV使用所隐含的相同最小剂量安全标准下进行优化，如果其他方向的剂量得到充分补偿，那么高剂量区在一个方向上的范围可以减少一半。进一步减小这种单侧剂量边界会降低靶区剂量的可信度，然而在90%可信度下实际的最小CTV剂量通常比最小PTV剂量超出处方剂量的20%。与使用PTV相比，在优化过程中纳入平滑的剂量效应关系会导致剂量分布更加集中，在肿瘤细胞杀伤概率和几何误差风险之间实现更好的平衡，并且对周围组织的剂量更低。发现在相同积分剂量下，肿瘤控制率提高超过20%是常见的，同时避开附近的OAR。这些结果对于剂量效应关系和靶区异质性的不确定性具有鲁棒性，并且不依赖于剂量分布中的“肩部”或“角部”。
