Small field proton irradiation for in vivo studies: Potential and limitations when adapting clinical infrastructure.

PURPOSE: To evaluate the dosimetric accuracy for small field proton irradiation relevant for pre-clinical in vivo studies using clinical infrastructure and technology. In this context additional beam collimation and range reduction was implemented. METHODS AND MATERIALS: The clinical proton beam line employing pencil beam scanning (PBS) was adapted for the irradiation of small fields at shallow depths. Cylindrical collimators with apertures of 15, 12, 7 and 5mm as well as two different range shifter types, placed at different distances relative to the target, were tested: a bolus range shifter (BRS) attached to the collimator and a clinical nozzle mounted range shifter (CRS) placed at a distance of 72cm from the collimator. The Monte Carlo (MC) based dose calculation engine implemented in the clinical treatment planning system (TPS) was commissioned for these two additional hardware components. The study was conducted with a phantom and cylindrical target sizes between 2 and 25mm in diameter following a dosimetric end-to-end test concept. RESULTS: The setup with the CRS provided a uniform dose distribution across the target. An agreement of better than5% between the planned dose and the measurements was obtained for a target with 3mm diameter (collimator 5mm). A 2mm difference between the collimator and the target diameter (target being 2 mm smaller than the collimator) sufficed to cover the whole target with the planned dose in the setup with CRS. Using the BRS setup (target 8mm, collimator 12mm) resulted in non-homogeneous dose distributions, with a dose discrepancy of up to 10% between the planned and measured doses. CONCLUSION: The clinical proton infrastructure with adequate beam line adaptations and a state-of-the-art TPS based on MC dose calculations enables small animal irradiations with a high dosimetric precision and accuracy for target sizes down to 3mm.

Dose calculation accuracy in particle therapy: Comparing carbon ions with protons.

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 cm3 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.

RBE variation in prostate carcinoma cells in active scanning proton beams: In-vitro measurements in comparison with phenomenological models.

PURPOSE: In-vitro radiobiological studies are essential for modelling the relative biological effectiveness (RBE) in proton therapy. The purpose of this study was to experimentally determine the RBE values in proton beams along the beam path for human prostate carcinoma cells (Du-145). RBE-dose and RBE-LETd (dose-averaged linear energy transfer) dependencies were investigated and three phenomenological RBE models, i.e. McNamara, Rørvik and Wilkens were benchmarked for this cell line. METHODS: Cells were placed at multiple positions along the beam path, employing an in-house developed solid phantom. The experimental setup reflected the clinical prostate treatment scenario in terms of field size, depth, and required proton energies (127.2-180.1 MeV) and the physical doses from 0.5 to 6 Gy were delivered. The reference irradiation was performed with 200 kV X-ray beams. Respective (α/ß) values were determined using the linear quadratic model and LETd was derived from the treatment planning system at the exact location of cells. RESULTS AND CONCLUSION: Independent of the cell survival level, all experimental RBE values were consistently higher in the target than the generic clinical RBE value of 1.1; with the lowest RBE value of 1.28 obtained at the beginning of the SOBP. A systematic RBE decrease with increasing dose was observed for the investigated dose range. The RBE values from all three applied models were considerably smaller than the experimental values. A clear increase of experimental RBE values with LETd parameter suggests that proton LET must be taken into consideration for this low (α/ß) tissue.

Experimental benchmarking of RayStation proton dose calculation algorithms inside and outside the target region in heterogeneous phantom geometries.

PURPOSE: 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.

Investigating the impact of alpha/beta and LETd on relative biological effectiveness in scanned proton beams: An in vitro study based on human cell lines.

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 (LETd ) and the sensitivity factor (α/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 (α/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. LETd 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 % (RBE90 ) and 10 % (RBE10 ) of cell survival, and survival after a 0.5 Gy dose (RBE0.5Gy ), 2 Gy dose (RBE2Gy ), and 6 Gy dose (RBE6Gy ). RESULTS: LETd 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 (α/ß)X ratios (FaDu, HaCat), the LETd did not impact on the RBE. For low (α/ß)X cell lines (Du145, SKMel), LQ-derived survival curves indicated a clear correlation of LETd and RBE. RBE90 values up to 2.9 and RBE10 values between 1.4 and 1.8 were obtained. Model-derived RBE predictions slightly overestimated the RBE for the high (α/ß)X cell lines, although all models except the Jones model provided RBE values within the experimental uncertainty. For low (α/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 (α/ß)X was observed to be a major influencing factor for the RBE of protons and its sensitivity toward LETd changes. RBE prediction models are applicable for high (α/ß)X cell lines but do not estimate RBE values with sufficient accuracy in low (α/ß)X cell lines.

Phantom design and dosimetric characterization for multiple simultaneous cell irradiations with active pencil beam scanning.

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.