LET-modifying joint optimization for mixed-modality photon-proton treatment planning

As depth increases, linear energy transfer (LET) rises toward the distal edge of the Bragg peak, boosting the radiobiological effectiveness (RBE). To manage the biological variation and limit normal-tissue damage, LET-modifying objective functions on, e.g., dose-weighted LET or dirty dose and/or usage of variable RBE models were introduced. Because shaping LET by proton irradiation alone has its limits, this work proposes to jointly optimize mixed-modality proton-photon treatments based on directly LET-modifying objective functions. The investigated objective functions rely on either dose-weighted LET or dirty dose concepts. To formulate a consistent combined optimization problem, the contribution of secondary electron LET in photon treatments is considered (and discussed) as well. Combined dose/LET calculation and optimization are realized in the open source toolkit matRad. Phantom plans as well as a patient plans are optimized for analysis on the method, combining five proton fractions with 25 photon fractions. Dose-optimized combined plans are used as a reference. The reference plan shows that protons are, in general, dosimetrically superior and thus preferred, with photons aiding in achieving conformity. The introduction of LET modified objectives locally modifies the proton contribution in the targeted regions of interest. Especially at the distal edge, the photon contribution increases to move high-LET/dirty dose out of the OARs. Dirty dose objectives seem to allow a more comprehensive steering of the high-LET regions compared to LETxDose. Incorporating LET-based objectives into a jointly optimized proton-photon system allows for improved dose conformity and reduced high-LET exposure in critical regions in proximity to the distal proton edge. This approach enables the utilization of modality-specific strengths and can contribute to safer, more effective treatment plans.