Integrating prompt gamma range verification and relative biological effectiveness in multicriterial proton treatment planning

将即时伽玛范围验证和相对生物有效性整合到多标准质子治疗计划中

• 批准号: 441208898
• 负责人: Professor Dr. Karl-Heinz Küfer
• 金额: --
• 依托单位: Fraunhofer-Institut für Techno- und Wirtschaftsmathematik (ITWM)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/441208898?language=en
• 关键词: Integrating; prompt; gamma; range; verification

Proton radiotherapy is becoming an increasingly widespread treatment option against cancer which allows to tightly confine the high dose area to the tumor target volume and spare organs at risk, because the dose maximum is deposited at the end of the range, the so-called Bragg peak. Two aspects however make the planning and delivery for proton therapy challenging: 1) The Bragg peak position is sensitive to anatomical variations and uncertainties in the knowledge of the tissue stopping properties, and 2) the relative biological effectiveness (RBE) of protons is variable. The issue of Bragg peak positioning is currently addressed in clinical practice by avoiding beam directions that would place the sharp distal dose fall-off directly in front of critical structures, by adding safety margins, and by robust optimization approaches, at the cost of sacrificing some dose conformity. Moreover, in research settings prompt gamma (PG) emissions induced by the irradiation are used for in-vivo range verification, enabling a monitoring of the dose delivery ideally in real-time. The variable RBE is currently disregarded in clinical practice by assuming a constant value of 1.1, but possible implications of a variable RBE scheme are subject of increasing attention. The overarching goal of this project is to develop models and algorithms which incorporate PG range verification and biological effectiveness in terms of linear energy transfer (LET) and RBE as new criteria in a research proton planning system based on multicriteria optimization (MCO). This MCO system is ideally suited to study the trade-offs of conflicting planning goals, and it will be used to gain novel insights into the clinical potential of adding PG range verification and LET/RBE considerations to standard dose metrics of target coverage and normal tissue sparing. Optimization of PG monitoring includes the identification and boosting of the most suited pencil beam spots, and predicting the final PG image quality including the response models of several PG cameras currently under development. Objective functions for PG monitoring and LET/RBE quantification will be integrated in an MCO solver, and the Pareto front will be approximated by generating a database of plans. The Pareto front will be explored by using a graphical user interface including, if necessary, non-convex navigation. Local LET/RBE variations will be modeled, and tools to specifically increase or decrease the LET/RBE of subareas will be developed. Finally, in a planning study the new system is used for investigating the trade-offs between tumor dose, organ at risk sparing, LET/RBE variations, and suitability for PG monitoring, which ultimately aims at better utilization of the advantageous properties of proton radiotherapy to improve the clinical outcomes for cancer patients.

质子放射治疗正在成为一种越来越广泛的癌症治疗选择，它可以将高剂量区域严格限制在肿瘤靶体积和备用危险器官，因为剂量最大值沉积在范围的末端，即所谓的布拉格峰。然而，两个方面使得质子治疗的规划和递送具有挑战性：1）布拉格峰位置对组织停止特性的知识中的解剖变化和不确定性敏感，以及2）质子的相对生物有效性（RBE）是可变的。布拉格峰定位的问题目前在临床实践中通过避免将急剧的远端剂量下降直接放置在关键结构前面的射束方向、通过增加安全裕度以及通过稳健的优化方法来解决，代价是牺牲一些剂量一致性。此外，在研究环境中，由辐照引起的瞬发伽马（PG）发射用于体内范围验证，从而能够理想地实时监测剂量递送。变量RBE目前在临床实践中被忽略，假设恒定值为1.1，但变量RBE计划的可能影响越来越受到关注。该项目的总体目标是开发模型和算法，将PG范围验证和生物学有效性的线性能量转移（LET）和RBE作为新的标准，在研究质子规划系统的基础上多准则优化（MCO）。该MCO系统非常适合研究相互冲突的计划目标的权衡，并且将用于获得对将PG范围验证和LET/RBE考虑因素添加到目标覆盖和正常组织保留的标准剂量度量的临床潜力的新见解。PG监控的优化包括识别和增强最合适的笔形波束点，并预测最终的PG图像质量，包括目前正在开发的几个PG相机的响应模型。PG监测和LET/RBE量化的目标函数将被集成到MCO求解器中，帕累托前沿将通过生成计划数据库来近似。帕累托前沿将通过使用图形用户界面进行探索，如有必要，包括非凸导航。将对局部LET/RBE变化进行建模，并开发专门增加或减少分区LET/RBE的工具。最后，在一项计划研究中，新系统用于调查肿瘤剂量、危险器官保留、LET/RBE变化和PG监测的适用性之间的权衡，其最终目的是更好地利用质子放射治疗的有利特性来改善癌症患者的临床结局。