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Aims Proton beam therapy (PBT) has increasingly been applied for the treatment of young children when radiotherapy is needed. The treatment requires intensive multimodality care and is logistically demanding. In this analysis, we evaluated our experiences in treating infants with tumours of the central nervous system with PBT. Materials and methods Children younger than 2 years of age treated with PBT for central nervous system tumours enrolled in the prospective registry study KiProReg were retrospectively analysed. Information on patient characteristics, treatment, toxicities and outcome were evaluated. Adverse events were classified according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE V4.0) before, during and after PBT. Results Between September 2013 and June 2018, 51 infants were eligible. The median age was 19 months (range 11–23 months) at the time of PBT. Tumour entities were ependymoma (51.0%), atypical teratoid rhabdoid tumour (39.0%), high-grade glioma (6.0%), pineoblastoma (2.0%) and medulloblastoma (2.0%). The prescribed median total dose was 54.0 Gy (range 45.0–59.4 Gy). Most received local radiotherapy. In four patients, craniospinal irradiation followed by a boost to the local tumour bed was applied. The median follow-up time was 42.0 months (range 7.3–86.2 months). The estimated 3-year local control, progression-free survival and overall survival rates for all patients were 62.7, 47.1 and 76.5%, respectively. During radiotherapy, 24 events of higher-grade (CTCAE ≥ °III) toxicities were reported. Interruption of radiotherapy for more than 2 days was due to infection (n = 3) or shunt complication (n = 2). Unexpected hospitalisation during radiotherapy affected 12 patients. Late adverse events attributable to radiotherapy included endocrinopathy (CTCAE °II; 7.8%), new onset of hearing loss (CTCAE °III; 5.8%) and visual impairment (CTCAE °IV; 1.9%). Transient radiation-induced imaging changes occurred in five patients (9.8%). Conclusions Our study indicates that PBT is feasible for very young children with central nervous system tumours, at least in the short term. However, it requires challenging interdisciplinary medical care and high logistical effort. For evaluation of late effects, longer follow-up and evaluation of neurocognitive outcome are desirable. More data have to be gathered to further define the role of radiotherapy in infants over time.

Survivors of pediatric brain tumors are susceptible to neurovascular disease after radiotherapy, with dose to the chiasm or Circle of Willis (CW) as risk factors. The aims of this study were to develop a delineation atlas of neurovascular structures, to investigate the doses to these structures in relation to tumor location and to investigate potential dose surrogates for the CW dose. An atlas of the CW, the large intracranial arteries and the suprasellar cistern (SC) was developed and validated. Thirty proton plans from previously treated pediatric brain tumor patients were retrieved and grouped according to tumor site: 10 central, 10 lateralized, and 10 posterior fossa tumors. Based on the atlas, neurovascular structures were delineated and dose metrics (mean dose (Dmean) and maximal dose (Dmax)) to these structures and the already delineated chiasm were evaluated. The agreement between dose metrics to the CW vs. chiasm/SC was investigated. The minimal Hausdorff distance (HDmin) between the target and SC was correlated with the SC Dmean. The median Dmean/Dmax to the CW were 53 Gy(RBE)/55 Gy(RBE) in the central tumors, 18 Gy(RBE)/25 Gy(RBE) in the lateralized tumors and 30 Gy(RBE)/49 Gy(RBE) in the posterior fossa tumors. There was a good agreement between the Dmax/Dmean to the CW and the SC for all cases (R2=0.99), while in the posterior fossa group, the CW Dmax was underestimated when using the chiasm as surrogate (R2=0.76). Across all patients, cases with HDmin < 10 mm between the target and the SC received the highest SC Dmean. The pattern of dose to neurovascular structures varied with the tumor location. For all locations, SC doses could be used as a surrogate for CW doses. A minimal distance larger than 10 mm between the target and the SC indicated a potential for neurovascular dose sparing.

Purpose/objective: Quantification of surface dose within the first few hundred water equivalent µm is challenging. Nevertheless, it is of large interest for the proton therapy community to study dose effects in the skin. The experimental determination is affected by the detector properties, such as the detector volume and material. The International Commission on Radiation Units and Measurements in its report 39 recommends assessing the skin dose at a depth of 0.07 mm. The aim of this study is the estimation of the absorbed dose at and around a depth of 70 µm. We used various dosimetric approaches in conjunction with proton pencil beam scanning delivery to determine the skin dose in a clinical setting. Material/methods: Five different detectors were tested for determining the surface dose in water: EBT3 and HD-V2 GAFCHROMIC™ radiochromic film, LiF:Mg,Ti thermoluminescent dosimeter, IBA PPC05 plane-parallel ionization chamber, and PTW 23391 extrapolation chamber. The irradiation setup consisted of quasi-monoenergetic scanned proton pencil beams with kinetic energies of 100, 150, and 226.7 MeV, respectively. Radiochromic films were placed within a vertical stack and in wedge geometry and were analyzed with FilmQA Pro™ adopting triple channel dosimetry. The extrapolation chamber PTW 23391, which served as a reference in the current work, was used in a conventional ionization chamber setup with a fixed electrode gap of 2 mm. Three Kapton® entrance windows with thicknesses of 25, 50, and 75 µm were employed. Thermoluminescent dosimeters were provided as powder and were pressed onto a sheet of aluminum. Furthermore, the Monte Carlo code TOol for PArticle Simulation (TOPAS) in version 3.1.p2 was used to model an IBA pencil beam scanning nozzle and score dose to water in a water phantom. Results: The resulting depth dose curves were normalized to their 100% dose at the reference depth of 3 cm. We obtained the skin doses with the extrapolation chamber and with TOPAS. For the experimental approach this resulted in 79.7 ± 0.3%, 86.0 ± 0.6%, and 87.1 ± 0.1% for the proton energies 100, 150, and 226.7 MeV, respectively. The results for TOPAS were 80.1 ± 0.2% (100 MeV), 87.1 ± 0.5% (150 MeV), and 86.9 ± 0.4% (226.7 MeV), respectively. Based on the experimental results of the skin dose, we provided a clinically relevant surface extrapolation factor for the common measurement methods. This allows the result of the first measurement depth of a detector to be scaled to the dose at the skin depth. Most practical would be the use of the surface extrapolation factor for the PPC05 chamber, due to its direct reading, the wide availability in clinics and the low uncertainties. The calculated factors were 0.986 ± 0.004 for 100 MeV, 0.961 ± 0.008 for 150 MeV, and 0.963 ± 0.003 for 226.7 MeV. Conclusions: In this study, dissimilar experimental approaches were evaluated with respect to measurements at depths close to the surface. The experimental depth dose curves are in good agreement with the simulation with TOPAS Monte Carlo. To the author's knowledge this was the first experimental determination of the skin dose according to the International Commission on Radiation Units and Measurements 39 definition in proton pencil beam scanning.

Some clinical indications require small fields with sharp lateral dose gradients, which is technically challenging in proton beam therapy. This holds especially true for low-range fields applied with the spot scanning technique, where large beam profiles entering from the beam-line or the insertion of range shifting blocks lead to large lateral gradients. We regard the latter case and solve it by shifting the range shifting block far upstream in conjunction with a collimating aperture close to the patient. The experiments of the current work are based on a commercial proton therapy treatment head designed for several delivery modes. In a research environment of the spot-scanning delivery mode a range shifter is inserted downstream of the scanning magnets in a slot which is usually employed only in a scattering delivery mode. This configuration is motivated by equations assuming a simple model of proton transport. In the experiments lateral dose planes are acquired with a scintillation screen and radiochromic films. Dose distributions are calculated with the Monte Carlo dose engine of the RayStation treatment planning system. We demonstrate that proton fields with 80%–20% lateral dose fall-off values between 1.4 mm and 4.0 mm can be achieved for water equivalent depths between 0 cm and 10 cm. The simulated lateral dose profiles agree with the experimental dose profiles. The sharpening of the field edges is set off by a broadening of the proton spots towards the center of the fields. This limits the clinical application mainly to small fields for which the distal and proximal conformality is of minor importance.

To assess if apertures shall be mounted upstream or downstream of a range shifting block if these field-shaping devices are combined with the pencil-beam scanning delivery technique (PBS). The lateral dose fall-off served as a benchmark parameter. Both options realizing PBS-with-apertures were compared to the uniform scanning mode. We also evaluated the difference regarding the out-of-field dose caused by interactions of protons in beam-shaping devices. The potential benefit of the downstream configuration over the upstream configuration was estimated analytically. Guided by this theoretical evaluation a mechanical adapter was developed which transforms the upstream configuration provided by the proton machine vendor to a downstream configuration. Transversal dose profiles were calculated with the Monte-Carlo based dose engine of the commercial treatment planning system RayStation 6. Two-dimensional dose planes were measured with an ionization chamber array and a scintillation detector at different depths and compared to the calculation. Additionally, a clinical example for the irradiation of the orbit was compared for both PBS options and a uniform scanning treatment plan. Assuming the same air gap the lateral dose fall-off at the field edge at a few centimeter depth is 20% smaller for the aperture-downstream configuration than for the upstream one. For both options of PBS-with-apertures the dose fall-off is larger than in uniform scanning delivery mode if the minimum accelerator energy is 100 MeV. The RayStation treatment planning system calculated the width of the lateral dose fall-off with an accuracy of typically 0.1 mm-0.3 mm. Although experiments and calculations indicate a ranking of the three delivery options regarding lateral dose fall-off, there seems to be a limited impact on a multi-field treatment plan.

Respiratory induced organ motion poses a major challenge for high-precision radiotherapy such as pencil beam scanning proton therapy (PBS). In order to employ PBS for target regions affected by respiratory motion, the implementation of dedicated motion mitigation techniques should be considered and residual uncertainties need to be assessed. For the latter purpose, a routine simulating the delivery of a scanned proton beam to a moving target was developed and implemented in the commercial treatment planning system RayStation. The time structure of the beam delivery was extracted from electronic irradiation protocols of the delivery system. Alternatively to electronic irradiation protocols, an empirical time model of the beam delivery was created to allow for prospective estimations of interplay effects between target motion and pencil beam scanning. The experimental validation of the routine was performed using a two-dimensional ionization chamber array and a dynamic phantom. A 4D CT data set, including 10 respiratory phases, provided the spatial temporal information about the phantom motion. The dosimetric comparison of the measured and the calculated dose distribution yielded gamma pass rates above 96% using a 3% dose difference and a 3mm distance to agreement criterion. Thus, a tool for the evaluation of interplay effects is available in a clinical software environment and patient-specific quality assurance can be extended to dynamic treatment scenarios.

Purpose To commission the treatment planning system (TPS) RayStation for proton therapy including beam models for spot scanning and for uniform scanning. Methods Tests consist of procedures from ESTRO booklet number 7, the German DIN for constancy checks of TPSs, and extra tests checking the dose perturbation function. The dose distributions within patients were verified in silico by a comparison of 65 clinical treatment plans with the TPS XiO. Dose-volume parameters, dose differences, and three-dimensional gamma-indices serve as measures of similarity. The monthly constancy checks of Raystation have been automatized with a script. Results The basic functionality of the software complies with ESTRO booklet number 7. For a few features minor enhancements are suggested. The dose distribution in RayStation agrees with the calculation in XiO. This is supported by a gamma-index (3 mm/3%) pass rate of >98.9% (median over 59 plans) for the volume within the 20% isodose line and a difference of V 95 of the PTV (median over 59 plans). If spot scanning is used together with a range shifter, the dose level calculated by RayStation can be off by a few percent. Conclusions RayStation can be used for the creation of clinical proton treatment plans. Compared to XiO RayStation has an improved modelling of the lateral dose fall-off in passively delivered fields. For spot scanning fields with range shifter blocks an empirical adjustment of monitor units is required. The computation of perturbed doses also allows the evaluation of the robustness of a treatment plan.

Purpose : In light-ion beam dosedelivery with the scanning technique the spacing between adjacent spots is an important parameter during treatment planning. In order to study the effect of spot spacing on dose conformity and robustness for single field uniform dose configurations, fundamental geometrical properties of placement of Gaussian beamlets are explored. In particular, the dependence of penumbra width and flatness on spot width and spot spacing is investigated. Methods : Infinitesimal calculus and analytical methods are used to derive simple expressions for the lateral penumbra and the flatness of one-dimensional dose profiles in continuous scanning and uniform discrete spot scanning. In the same way expressions for the fundamental modes of perturbation of the spot sequence are developed. A numerical, matrix-based approach is followed to optimize weights spot-by-spot. Results : Generally the lateral penumbra widths lie between 1.13 σ b and 1.68 σ b with σ b being the standard deviation of the beam spot profile. For regularly placed spots of equal weight with spot spacing λ the lateral penumbra is given by 1.68 σ ′ where σ ′ results from quadratic subtraction of λ / 12 from σ b . The quantization error is identified as additional parameter describing the lateral dose conformity. It’s variance is given by λ 2 / 12 for a bunch of spots with uniform weights. The matrix-based optimization of weights for a one-dimensional dose box results in a lateral penumbra of typically 1.4 σ b . This value reduces to about 1.3 σ b if also the positions of the beam spots are optimized for the considered field size. The analytical formulas for uniform discrete scanning can be used as rough approximations of the best-case scenarios for weight-optimized dose profiles if the spot spacing is defined as effective spot spacing. Conclusions : The trade-off between flatness, quantization error, and robustness on the one side and penumbra width on the other side can be described analytically for equally weighted spots. Treatment planning systems often perform a least-squares optimization of the individual spot weights which results in smaller lateral penumbras and smaller quantization errors than for uniform discrete scanning. However, the benefit of this weight optimization decreases with increasing λ (in the regime λ > σ b ). The spot spacing, which is obtained from the scenario that the optimization objective is met by uniform discrete scanning, poses a sharp upper limit for the spot spacing λ in weight optimization methods.

Theoretical considerations predicted the feasibility of K-edge x-ray computed tomography (CT) imaging using energy discriminating detectors with more than two energy bins. This technique enables material-specific imaging in CT, which in combination with high-Z element based contrast agents, opens up possibilities for new medical applications. In this paper, we present a CT system with energy detection capabilities, which was used to demonstrate the feasibility of quantitative K-edge CT imaging experimentally. A phantom was imaged containing PMMA, calcium-hydroxyapatite, water and two contrast agents based on iodine and gadolinium, respectively. Separate images of the attenuation by photoelectric absorption and Compton scattering were reconstructed from energy-resolved projection data using maximum-likelihood basis-component decomposition. The data analysis further enabled the display of images of the individual contrast agents and their concentrations, separated from the anatomical background. Measured concentrations of iodine and gadolinium were in good agreement with the actual concentrations. Prior to the tomographic measurements, the detector response functions for monochromatic illumination using synchrotron radiation were determined in the energy range 25 keV-60 keV. These data were used to calibrate the detector and derive a phenomenological model for the detector response and the energy bin sensitivities.

A counting-mode line detector has been evaluated at a synchrotron radiation source in order to assess its performance for imaging applications. The x-ray detector is based on 3 mm thick CdZnTe arrays with 1 mm pixel pitch and multi-threshold counting electronics. Data readout has been performed in threshold scan mode to provide maximum energy dispersion. The acquired energy spectra are interpreted regarding the characteristics of a periodic source and pulse pile-up in the detector. In particular, energy response and rate behavior of single-photon and double-photon events are investigated. Count rate dynamics are studied up to incident rates of . A further subject of the investigation is the variance of the observed counting rate. Linearity in the energy domain is tested between 40 keV and 140 keV.

Proton therapy for non-ocular tumours in children is a relatively new development in Europe. Main arguments for proton therapy are the reduced risk for secondary cancers as well as a more precise sparing of organs at risk (OAR). Due to interdisciplinary advances more children survive their childhood cancer and have to deal with late effects of their primary cancer treatment. Children are by about a factor of ten more sensitive to radiation-induced malignancies than adults. Due to a smaller body volume, the scattering is more significant than in the (larger) body of an adult. At the West German Proton Therapy Centre (WPE) 276 children were treated between 06/2013 and 05/2016. 190 patients were 0–10 years, 86 were 11–18 years old. 154 patients needed anaesthesia. The most frequent malignancies treated were CNS tumours (145) and sarcomas (107). Very precise radiation volumes can be achieved e.g. in retroperitoneal malignancies, cranio-spinal axes, ENT and CNS tumours. Sparing of OAR, such as brain stem, hippocampus, pituitary gland, cochlea, chiasma, lacrimal and salivary glands is very important to reduce late side-effects and preserve quality of life. A main challenge of proton therapy remains the prolonged time for treatment planning. Metal or breathing movements in the irradiated volume pose additional challenges and sometimes develop into a pitfall during treatment planning. Similar problems occur, if density changes happen (e.g. growing or shrinking of cysts in the PTV, air inclusions). An adhoc adaption of the treatment plan is not simply arranged, but takes time.

Acquisition of quasi‐monoenergetic ("pristine") depth‐dose curves is an essential task in the frame of commissioning and quality assurance of a proton therapy treatment head. For pencil beam scanning delivery modes this is often accomplished by measuring the integral ionization in a plane perpendicular to the axis of an unscanned beam. We focus on the evaluation of three integral detectors: two of them are plane‐parallel ionization chambers with an effective radius of 4.1 cm and 6.0 cm, respectively, mounted in a scanning water phantom. The third integral detector is a 6.0 cm radius multilayer ionization chamber. The experimental results are compared with the corresponding measurements under broad field conditions, which are performed with a small radius plane‐parallel chamber and a small radius multilayer ionization chamber. We study how a measured depth‐dose curve of a pristine proton field depends on the detection device, by evaluating the shape of the depth‐dose curve, the relative charge collection efficiency, and intercomparing measured ranges. Our results show that increasing the radius of an integral chamber from 4.1 cm to 6.0 cm increases the collection efficiency by 0%–3.5% depending on beam energy and depth. Ranges can be determined by the large electrode multilayer ionization chamber with a typical uncertainty of 0.4 mm on a routine basis. The large electrode multilayer ionization chamber exhibits a small distortion in the Bragg Peak region. This prohibits its use for acquisition of base data, but is tolerable for quality assurance. The good range accuracy and the peak distortion are characteristics of the multilayer ionization chamber design, as shown by the direct comparison with the small electrode counterpart. PACS number: 87.55.Qr

We present here a novel method for using a single device in the daily quality assurance (QA) of pencil beam scanning (PBS) proton beams and an improved method for uniform scanning (US). The device can be used to measure the spot position, spot sigma, range, output, collinearity of the X‐ray system and proton beam, and to QA the first scatterers and a number of other imaging and mechanical checks. We have performed the daily QA according to this procedure for more than six months in both a PBS gantry and a US gantry. All of the tests were found to be sensitive and accurate enough to determine if the property being tested is within the tolerance. The output has remained within the ±2% tolerance, with the majority of measurements within ±1%, and the range was within ±0.5mm. The collinearity of the proton beam in both gantries is within the ±1mm tolerance in both X and Y directions for all measurements. A novel procedure to measure the functionality of the first scatterers in the US gantry is included in the QA procedure. It was found to be sensitive enough to pick up the thinnest scatterer of 0.6 mm in both possible failure methods — when it always remains in the beam or in the case when it never goes into the beam. The daily QA procedure presented here can be implemented at PBS or US proton therapy centers with a minimal outlay for equipment and setup time. The procedure can be performed in less than 30 min, and has been found to be accurate and reliable enough for the QA of a proton therapy gantry before patient treatment every day. PACS number: 87.55.Qr

A multichannel SigmaDelta-type analog-to-digital converter has been designed for data readout in CT scanners. A test-structure with a 4 times 4 photodetector array has been fabricated in a 0.8 mum CMOS process. Aiming at an integrated solution towards a 'digital pixel', each sensor element is formed by a photodiode and a third-order SigmaDelta-modulator. The switched-capacitor circuitry has been realized as a fully differential-path design. Test measurements have been carried out and analyzed in terms of dynamic range and noise. Simulations on layout level have been performed. A digital post-processing scheme has been devised for decimation and low-pass filtering of the modulator outputs

Purpose: To describe the design and initial testing of a large diameter multilayerionization chamber (MLIC) system for water equivalent range measurements of pristine proton fields. Method and Materials: The MLIC uses a large 120 mm physical diameter collecting cross‐section in a stacked vented parallel plate geometry of 180 layers spaced 0.8 mm apart. The plates are fabricated from printed circuit board material where copper traces have been etched to form the conductive elements for the ionization chambers. In addition a dedicated software package was developed to assist with device calibration data acquisition and analysis. Computer modeling of the MLIC was performed with the Monte Carlo (MC) code FLUKA. Radiological testing was performed in a dedicated proton pencil beam scanning (PBS) therapeutic delivery system. The energies tested varied from 100–230 MeV. A series of 10 pristine depth profiles were first acquired for reference within this energy range by longitudinally scanning a discrete parallel plate ionization chamber of 84 mm diameter in a water phantom. After a calibration routine was applied to the MLIC the same energies were tested with the MLIC and the results compared. Additional tests were performed at different fluence rates to evaluate changes in response to detector bias and charge quantum (QC) settings. Results: The analyzed data from the MC simulation and MLIC physical data compared within one mm to the water phantom reference data under the conditions tested. The MLIC results were not sensitive to bias setting but depended with fluence rate on the QC setting. Conclusion: The initial test of the new MLIC prototype provided satisfactory results with regard to water equivalent range accuracy in comparison to reference measurements from the PBS system. Some flexibility is provided with different fluence rates by adjusting the QC. The detailed results will be presented and discussed.

In the above titled paper (ibid., vol. 56, no. 4, pp. 1800-1809, Aug. 09), an error appeared in Table III. A corrected version of Table III is presented here.