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

• Applicants: Professor Dr. Karl-Heinz Küfer; Professorin Dr. Katia Parodi; Privatdozent Dr. Christian Thieke
• Subject Area: Medical Physics, Biomedical Technology
• Term: since 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 441208898

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.

• DFG Programme: Research Grants