  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.
