FRoG: An independent dose and LET_d prediction tool for proton therapy at ProBeam® facilities

Abstract

Particle therapy is becoming increasingly available worldwide for precise tumor targeting, its favorable depth dose deposition, and increased biological damage to tumor tissue compared to conventional photon therapy. As demand increases for improved robustness and conformality, nextgeneration secondary dose calculation engines are needed to verify treatment plans independently and provide estimates for clinical decision-making factors, such as dose-averaged linear energy transfer (LET d) and relative biological effectiveness (RBE). Method: FRoG (Fast dose Recalculation on GPU) has been installed and commissioned at the Danish Centre for Particle Therapy (DCPT). FRoG was developed for synchrotron-based facilities and has previously demonstrated good agreement with gold-standard Monte Carlo simulations and measurements. In this work, additions and modifications to FRoG's pencil beam algorithm to support the ion beam delivery with cyclotron-based technology as used at the DCPT, range shifter (RS) implementation, and robustness analysis methods are presented. FRoG dose predictions are compared to measurements and predictions of the clinical treatment planning system (TPS) Eclipse (Varian Medical Systems, Palo Alto, United States of America, CA, v.13.7.16) in both homogenous and heterogeneous scenarios using a solid-water/water and a half-head anthropomorphic phantom, respectively. Additional capabilities of FRoG are explored by performing a plan robustness analysis, analyzing dose and LET d for ten patients. Results: Mid-target measurements in spread-out Bragg Peaks (SOBP) were on average within −0.19% AE 0.30% and ≤0.5% of FRoG predictions for irradiations without and with RS, respectively. Average 3%/2mm 3D γ-analysis passing rates were 99.1% for~200 patient plan QA comparisons. Measurement with an anthropomorphic head-phantom yielded a γ-passing rate >98%. Overall, maximum target differences in D 02% of <2% between the TPS and FRoG were observed for patient plans. The robustness analysis study accounting for range, delivery, and positioning uncertainties revealed small differences in target dose and a maximum LET d VH 02% (LET d received by 2% of the volume having dose larger than 1% of maximum dose) values below 10.1 keV/µm to the brain stem. Conclusion: We demonstrate that auxiliary dose calculation systems like FRoG can yield excellent agreement to measurements comparable to clinical beam models. Through this work, application of FRoG as a secondary engine at third party cyclotron-based particle treatment facilities is now established for dose verification as well as providing further insight on LET d and variable RBE distributions for protons, currently absent from the standard clinical TPS.

A systematic review on the usage of averaged LET in radiation biology for particle therapy

“…• Only the primary protons [5,[117][118][119][120][121][122][123][124][125][126][127][128] • Primary and secondary protons 3 [14, • any particle with z = 1 (meaning also deuterons and tritons) [152] as described in [24] • all secondary particles (most noteworthy also He-3 and He-4) [27,[153][154][155][156], also covered by [24].…”

Development and Benchmarking of a Monte Carlo Dose Engine for Proton Radiation Therapy

“…In order to overcome these limitations, FRoG (Fast dose* Recalculation on GPU) has been introduced, an advanced analytical code capable of calculating dose, LET d (dose-weighted Linear Energy Transfer) and biological dose for the four particle beams available at HIT [19][20][21] and which is in use at other PT facilities in Europe (Centro Nazionale di Adroterapia Oncologica [21], Danish Centre for Particle Therapy [22]. High levels of agreement within 1-2% [19,21,23] were found comparing FLUKA and FRoG recalculated dose-volume-histograms (DVH) of proton and other light ion patient plans even for complex cases such as lung irradiation [23].…”

RBE for proton radiation therapy – a Nordic view in the international perspective

“…Limitations of analytical algorithms for proton dose calculations have started to be recognised [40] and Monte Carlo algorithms are increasingly recommended for better accuracy. These are indeed more demanding in terms of computational capacity, but the conditions improve by the increased implementation of faster calculations [23]. Similarly, uncertainties in calculating LET have also been shown to lead to rather large differences in reported values [38].…”

“…As a tool to compare different planning approaches and to estimate the possible risk for different field orientations, LET d calculations constitute a valuable addition to a strict dose calculation. Possibilities for LET d calculations are getting increasingly available both in commercial TPS and in dedicated software packages such as FRoG [23].…”

“…For tumours close to the brainstem and treated to prescribed doses at or above 54 Gy, the distal edge in the brainstem is only allowed for one out of the minimum three fields. In selected cases, the distribution of proton LET d values at the voxel level is calculated using FRoG [23] and the presence of elevated LET d in critical normal tissue is evaluated. If it is obvious that there is more than one beam having a distal edge in the brainstem, a correction of the beam arrangement would be considered by adjusting beam angles to avoid several beams having the distal edge in the same area according to recommendations from the National Cancer Institute Workshop on Proton Therapy for Children [24].…”