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The aim of the presented study was to complement existing literature on benchmarking proton dose by comparing dose calculations with experimental measurements in heterogeneous phantom. Points of interest inside and outside the target were considered to quantify the magnitude of calculation uncertainties in current and previous proton therapy practice that might especially have an impact on the dose in organs at risk (OARs). Methods: The RayStation treatment planning system (RaySearch Laboratories), offering two dose calculation algorithms for pencil beam scanning in proton therapy, i.e., Pencil Beam (PB) and Monte Carlo (MC), was utilized. Treatment plans for a target located behind the interface of the heterogeneous tissues were generated. Dose measurements within and behind the target were performed in a water phantom with embedded slabs of various tissue equivalent materials and 24 PinPoint ionization chambers (PTW). In total 12 test configurations encompassing two different target depths, oblique beam incidence of 30 degrees and range shifter, were considered. Results: PB and MC calculated doses agreed equally well with the measurements for all test geometries within the target, including the range shifter (mean dose differences ± 3%). Outside the target, the maximum dose difference of 9% (19%) was observed for MC (PB) for the oblique beam incidence and inserted range shifter. Conclusion:The accuracy of MC dose algorithm was superior compared to the PB algorithm, especially outside the target volumes. MC based dose calculation should therefore be preferred in treatment scenarios with heterogeneities, especially to reduce clinically relevant uncertainties for OARs.

Purpose: A relative biological effectiveness (RBE) of 1.1 is commonly used in clinical proton therapy, irrespective of tissue type and depth. This in vitro study was conducted to quantify the RBE of scanned protons as a function of the dose-averaged linear energy transfer (LET d) and the sensitivity factor (a/ß) X. Additionally, three phenomenological models (McNamara, Rørvik, and Jones) and one mechanistic model (repair-misrepair-fixation, RMF) were applied to the experimentally derived data. Methods: Four human cell lines (FaDu, HaCat, Du145, SKMel) with differential (a/ß) X ratios were irradiated in a custom-designed irradiation setup with doses between 0 and 6 Gy at proximal, central, and distal positions of a 80 mm spread-out Bragg peak (SOBP) centered at 80 mm (setup A: proton energies 66.5-135.6 MeV) and 155 mm (setup B: proton energies 127.2-185.9 MeV) depth, respectively. LET d values at the respective cell positions were derived from Monte Carlo simulations performed with the treatment planning system (TPS, RayStation). Dosimetric measurements were conducted to verify dose homogeneity and dose delivery accuracy. RBE values were derived for doses that resulted in 90 % (RBE 90) and 10 % (RBE 10) of cell survival, and survival after a 0.5 Gy dose (RBE 0.5Gy), 2 Gy dose (RBE 2Gy), and 6 Gy dose (RBE 6Gy). Results: LET d values at sample positions were 1.9, 2.1, 2.5, 2.8, 4.1, and 4.5 keV/µm. For the cell lines with high (a/ß) X ratios (FaDu, HaCat), the LET d did not impact on the RBE. For low (a/ß) X cell lines (Du145, SKMel), LQ-derived survival curves indicated a clear correlation of LET d and RBE. RBE 90 values up to 2.9 and RBE 10 values between 1.4 and 1.8 were obtained. Model-derived RBE predictions slightly overestimated the RBE for the high (a/ß) X cell lines, although all models except the Jones model provided RBE values within the experimental uncertainty. For low (a/ß) X cell lines, no agreement was found between experiments and model predictions, that is, all models underestimated the measured RBE. Conclusions: The sensitivity parameter (a/ß) X was observed to be a major influencing factor for the RBE of protons and its sensitivity toward LET d changes. RBE prediction models are applicable for high (a/ß) X cell lines but do not estimate RBE values with sufficient accuracy in low (a/ß) X cell lines.

A new phantom was designed for in vitro studies on cell lines in horizontal particle beams. The phantom enables simultaneous irradiation at multiple positions along the beam path. The main purpose of this study was the detailed dosimetric characterization of the phantom which consists of various heterogeneous structures. The dosimetric measurements described here were performed under non-reference conditions. The experiment involved a CT scan of the phantom, dose calculations performed with the treatment planning system (TPS) RayStation employing both the Pencil Beam (PB) and Monte Carlo (MC) algorithms, and proton beam delivery. Two treatment plans reflecting the typical target location for head and neck cancer and prostate cancer treatment were created. Absorbed dose to water and dose homogeneity were experimentally assessed within the phantom along the Bragg curve with ionization chambers (ICs) and EBT3 films. LETd distributions were obtained from the TPS. Measured depth dose distributions were in good agreement with the Monte Carlo-based TPS data. Absorbed dose calculated with the PB algorithm was 4% higher than the absorbed dose measured with ICs at the deepest measurement point along the spread-out Bragg peak. Results of experiments using melanoma (SKMel) cell line are also presented. The study suggested a pronounced correlation between the relative biological effectiveness (RBE) and LETd, where higher LETd leads to elevated cell death and cell inactivation. Obtained RBE values ranged from 1.4 to 1.8 at the survival level of 10% (RBE10). It is concluded that dosimetric characterization of a phantom before its use for RBE experiments is essential, since a high dosimetric accuracy contributes to reliable RBE data and allows for a clearer differentiation between physical and biological uncertainties.

Purpose: This work presents the validation of an analytical pencil beam dose calculation algorithm in a commercial treatment planning system (TPS) for carbon ions by measurements of dose distributions in heterogeneous phantom geometries. Additionally, a comparison study of carbon ions versus protons is performed considering current best solutions in commercial TPS. Methods: All treatment plans were optimized and calculated using the RayStation TPS (RaySearch, Sweden). The dose distributions calculated with the TPS were compared with measurements using a 24-pinpoint ionization chamber array (T31015, PTW, Germany). Tissue-like inhomogeneities (bone, lung, and soft tissue) were embedded in water, while a target volume of 4 x 4 x 4 cm 3 was defined at two different depths behind the heterogeneities. In total, 10 different test cases, with and without range shifter as well as different air gaps, were investigated. Dose distributions inside as well as behind the target volume were evaluated. Results: Inside the target volume, the mean dose difference between calculations and measurements, averaged over all test cases, was 1.6% for carbon ions. This compares well to the final agreement of 1.5% obtained in water at the commissioning stage of the TPS for carbon ions and is also within the clinically acceptable interval of 3%. The mean dose difference and maximal dose difference obtained outside the target area were 1.8% and 13.4%, respectively. The agreement of dose distributions for carbon ions in the target volumes was comparable or better to that between Monte Carlo (MC) dose calculations and measurements for protons. Percentage dose differences of more than 10% were present outside the target area behind bone-lung structures, where the carbon ion calculations systematically over predicted the dose. MC dose calculations for protons were superior to carbon ion beams outside the target volumes. Conclusion:The pencil beam dose calculations for carbon ions in RayStation were found to be in good agreement with dosimetric measurements in heterogeneous geometries for points of interest located within the target. Large local discrepancies behind the target may contribute to incorrect dose predictions for organs at risk.