Validation of the Quantum Physics Processes Underlying the Integrated Optimization of Proton FLASH Radiotherapy

Abstract

FLASH is a new treatment modality that requires optimization of dose, dose rate, and LET. Here we validate these three quantities under FLASH conditions, which includes the quantum uncertainty in the time-dependent instantaneous dose rate (IDR) curves and LET spectra that underlie the newly proposed integrated optimization framework. Measurements of dose, IDR, and LET were performed at the Emory Proton Therapy Center using a FLASH proton beam with a nominal energy of 250 MeV and a 3D printed ridge filter. Because 3D printing resin is made from a proprietary chemical formula, we developed a method for realistically characterizing and modeling the material in simulations. Absolute dose in 3D space was measured using a 2D MatriXX PT detector as well as by a novel 4D multi-layer strip ionization chamber (MLSIC), which also simultaneously measures IDR. Further timing data was measured in the secondary beam by detecting prompt gammas using a Minipix Timepix3; a second detector, Advapix Timepix3, was used to measure LET. To account for the quantum mechanical nature of particle transport, we developed a technique for detecting individual protons within a high flux primary beam, which was necessary for properly measuring LET spectra. TOPAS simulations agreed with measurement, with absolute dose typically having a gamma passing rate of at least 95% (3 mm/3% criteria). Likewise, IDR and LET showed good agreement, with averaged IDR values agreeing within 0.3% with fluctuations on the order of 10%, and LET distributions overlapping by at least 85% and showing an increase in high LET components (greater than 4 keV/um) with increasing depth. As LET and FLASH optimization continues to grow in popularity, measuring IDR, LET, and dose will become even more important, and we expect that the methods described here will prove to be useful tools in radiotherapy treatment planning and QA.