Dose- rather than fluence-averaged LET should be used as a single-parameter descriptor of proton beam quality for radiochromic film dosimetry.

The dose response of Gafchromic EBT3 films exposed to proton beams depends on the dose, and additionally on the beam quality, which is often quantified with the linear energy transfer (LET) and, hence, also referred to as LET quenching. Fundamentally different methods to determine correction factors for this LET quenching effect have been reported in literature and a new method using the local proton fluence distribution differential in LET is presented. This method was exploited to investigate whether a more practical correction based on the dose- or fluence-averaged LET is feasible in a variety of clinically possible beam arrangements. The relative effectiveness (RE) was characterized within a high LET spread-out Bragg peak (SOBP) in water made up by the six lowest available energies (62.4-67.5 MeV, configuration " b 1 ") resulting in one of the highest clinically feasible dose-averaged LET distributions. Additionally, two beams were measured where a low LET proton beam (252.7 MeV) was superimposed on " b 1 ", which contributed either 50% of the initial particle fluence or 50% of the dose in the SOBP, referred to as configuration " b 2 " and " b 3 ," respectively. The proton LET spectrum was simulated with GATE/Geant4 at all measurement positions. The net optical density change differential in LET was integrated over the local proton spectrum to calculate the net optical density and therefrom the beam quality correction factor. The LET dependence of the film response was accounted for by an LET dependence of one of the three parameters in the calibration function and was determined from inverse optimization using measurement " b 1 ." This method was then validated on the measurements of " b 2 " and " b 3 " and subsequently used to calculate the RE at 900 positions in nine clinically relevant beams. The extrapolated RE set was used to derive a simple linear correction function based on dose-averaged LET ( L d ) and verify the validity in all points of the comprehensive RE set. The uncorrected film dose deviated up to 26% from the reference dose, whereas the corrected film dose agreed within 3% in all three beams in water (" b 1 ", " b 2 " and " b 3 "). The LET dependence of the calibration function started to strongly increase around 5 keV/μm and flatten out around 30 keV/μm. All REs calculated from the proton fluence in the nine simulated beams could be approximated with a linear function of dose-averaged LET (RE = 1.0258-0.0211 μm/keV L d ). However, no functional relationship of RE- and fluence-averaged LET could be found encompassing all beam energies and modulations. The film quenching was found to be nonlinear as a function of proton LET as well as of the dose-averaged LET. However, the linear relation of RE on dose-averaged LET was a good approximation in all cases. In contrast to dose-averaged LET, fluence-averaged LET could not describe the RE when multiple beams were applied.

Resch AF ，Heyes PD ，Fuchs H ，Bassler N ，Georg D ，Palmans H ... -  《-》

Benchmarking a GATE/Geant4 Monte Carlo model for proton beams in magnetic fields.

Magnetic resonance guidance in proton therapy (MRPT) is expected to improve its current performance. The combination of magnetic fields with clinical proton beam lines poses several challenges for dosimetry, treatment planning and dose delivery. Proton beams are deflected by magnetic fields causing considerable changes in beam trajectories and also a retraction of the Bragg peak positions. A proper prediction and compensation of these effects is essential to ensure accurate dose calculations. This work aims to develop and benchmark a Monte Carlo (MC) beam model for dose calculation of MRPT for static magnetic fields up to 1 T. Proton beam interactions with magnetic fields were simulated using the GATE/Geant4 toolkit. The transport of charged particle in custom 3D magnetic field maps was implemented for the first time in GATE. Validation experiments were done using a horizontal proton pencil beam scanning system with energies between 62.4 and 252.7 MeV and a large gap dipole magnet (B = 0-1 T), positioned at the isocenter and creating magnetic fields transverse to the beam direction. Dose was measured with Gafchromic EBT3 films within a homogeneous PMMA phantom without and with bone and tissue equivalent material slab inserts. Linear energy transfer (LET) quenching of EBT3 films was corrected using a linear model on dose-averaged LET method to ensure a realistic dosimetric comparison between simulations and experiments. Planar dose distributions were measured with the films in two different configurations: parallel and transverse to the beam direction using single energy fields and spread-out Bragg peaks. The MC model was benchmarked against lateral deflections and spot sizes in air of single beams measured with a Lynx PT detector, as well as dose distributions using EBT3 films. Experimental and calculated dose distributions were compared to test the accuracy of the model. Measured proton beam deflections in air at distances of 465, 665, and 1155 mm behind the isocenter after passing the magnetic field region agreed with MC-predicted values within 4 mm. Differences between calculated and measured beam full width at half maximum (FWHM) were lower than 2 mm. For the homogeneous phantom, measured and simulated in-depth dose profiles showed range and average dose differences below 0.2 mm and 1.2%, respectively. Simulated central beam positions and widths differed <1 mm to the measurements with films. For both heterogenous phantoms, differences within 1 mm between measured and simulated central beam positions and widths were obtained, confirming a good agreement of the MC model. A GATE/Geant4 beam model for protons interacting with magnetic fields up to 1 T was developed and benchmarked to experimental data. For the first time, the GATE/Geant4 model was successfully validated not only for single energy beams, but for SOBP, in homogeneous and heterogeneous phantoms. EBT3 film dosimetry demonstrated to be a powerful dosimetric tool, once the film response function is LET corrected, for measurements in-line and transverse to the beam direction in magnetic fields. The proposed MC beam model is foreseen to support treatment planning and quality assurance (QA) activities toward MRPT.

Padilla-Cabal F ，Alejandro Fragoso J ，Franz Resch A ，Georg D ，Fuchs H ... -  《-》

LET response variability of Gafchromic TM EBT3 film from a 60 Co calibration in clinical proton beam qualities.

Smith BR ，Pankuch M ，Hammer CG ，DeWerd LA ，Culberson WS ... -  《-》

A linear relationship for the LET-dependence of Gafchromic EBT3 film in spot-scanning proton therapy.

Anderson SE ，Grams MP ，Wan Chan Tseung H ，Furutani KM ，Beltran CJ ... -  《-》

Segment-averaged LET concept and analytical calculation from microdosimetric quantities in proton radiation therapy.

This work introduces the concept of segment-averaged linear energy transfer (LET) as a new approach to average distributions of LET of proton beams based on a revisiting of microdosimetry theory. The concept of segment-averaged LET is then used to generate an analytical model from Monte Carlo simulations data to perform fast and accurate calculations of LET distributions for proton beams. The distribution of energy imparted by a proton beam into a representative biological structure or site is influenced by the distributions of (a) LET, (b) segment length, which is the section of the proton track in the site, and (c) energy straggling of the proton beam. The distribution of LET is thus generated by the LET of each component of the beam in the site. However, the situation when the LET of each single proton varies appreciably along its path in the site is not defined. Therefore, a new distribution can be obtained if the particle track segment is decomposed into smaller portions in which LET is roughly constant. We have called "segment distribution" of LET the one generated by the contribution of each portion. The average of that distribution is called segment-averaged LET. This quantity is obtained in the microdosimetry theory from the average and standard deviation of the distributions of energy imparted to the site, segment length, and energy imparted per collision. All this information is calculated for protons of clinically relevant energies by means of Geant4-DNA microdosimetric simulations. Finally, a set of analytical functions is proposed for each one of the previous quantities. The presented model functions are fitted to data from Geant4-DNA simulations for monoenergetic beams from 100 keV to 100 MeV and for spherical sites of 1, 5, and 10 μm in diameter. The average differences along the considered energy range between calculations based on our analytical models and MC for segment-averaged dose-averaged restricted LET are -0.2 ± 0.7 keV/μm for the 1 μm case, 0.0 ± 0.9 keV/μm for the 5 μm case, and -0.3 ± 1.1 keV/μm for the 10 μm case, respectively. All average differences are below the average standard deviation (1σ) of the MC calculations. A new way of averaging LET for a proton beam is performed to incorporate the effects produced by the variation of stopping power of each individual proton along microscopic biological structures. An analytical model based on MC simulations allows for fast and accurate calculations of segment-averaged dose-averaged restricted LET for proton beams, which otherwise would need to be calculated from exhaustive MC simulations of clinical plans.

Bertolet A ，Baratto-Roldán A ，Cortés-Giraldo MA ，Carabe-Fernandez A ... -  《-》