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Background In order to locate an arteriovenous malformation, typically, a digital subtraction angiography (DSA) is carried out. To use the DSA for target definition an accurate image registration between CT and DSA is required. Carrying out a non-invasive, frameless procedure, registration of the 2D-DSA images with the CT is critical. A new software prototype is enabling this frameless procedure. The aim of this work was to evaluate the prototype in terms of targeting accuracy and reliability based on phantom measurements as well as with the aid of patient data. In addition, the user’s ability to recognize registration mismatches and quality was assessed. Methods Targeting accuracy was measured with a simple cubic, as well as with an anthropomorphic head phantom. Clearly defined academic targets within the phantoms were contoured on the CT. These reference structures were compared with the structures generated within the prototype. A similar approach was used with patient data, where the clinically contoured target served as the reference structure. An important error source decreasing the target accuracy comes from registration errors between CT and 2D-DSA. For that reason, the tools in BC provided to the user to check these registrations are very important. In order to check if the user is able to recognize registration errors, a set of different registration errors was introduced to the correctly registered CT and 2D-DSA image data sets of three different patients. Each of six different users rated the whole set of registrations within the prototype. Results The target accuracy of the prototype was found to be below 0.04 cm for the cubic phantom and below 0.05 cm for the anthropomorphic head phantom. The mean target accuracy for the 15 patient cases was found to be below 0.3 cm. In the registration verification part, almost all introduced registration errors above 1° or 0.1 cm were detected by the six users. Nevertheless, in order to quantify and categorize the possibility to detect mismatches in the registration process more data needs to be evaluated. Conclusion Our study shows, that the prototype is a useful tool that has the potential to fill the gap towards a frameless procedure when treating AVMs with the aid of 2D-DSA images in radiosurgery. The target accuracy of the prototype is similar to other systems already established in clinical routine.

Purpose The objectives of the work presented in this paper were to (1) implement a robust-optimization method for deliverable mixed-beam radiotherapy (MBRT) plans within a previously developed MBRT planning framework; (2) perform an experimental validation of the delivery of robust-optimized MBRT plans; and (3) compare PTV-based and robust-optimized MBRT plans in terms of target dose robustness and organs at risk (OAR) sparing for clinical head and neck and brain patient cases. Methods A robust-optimization method, which accounts for translational setup errors, was implemented within a previously developed treatment planning framework for MBRT. The framework uses a hybrid direct aperture optimization method combining column generation and simulated annealing. A robust plan was developed and then delivered to an anthropomorphic head phantom using the Developer Mode of a TrueBeam linac. Planar dose distributions were measured and compared to the planned dose. Robust-optimized and PTV-based plans were developed for three clinical patient cases consisting of two head and neck cases and one brain case. The plans were compared in terms of the robustness to 5 mm shifts of the target volume dose as well as in terms of OAR sparing. Results Using a gamma criterion of 3%/2 mm and a dose threshold of 10%, the agreement between film measurements and dose calculations was better than 97.7% for the total plan and better than 95.5% for the electron component of the plan. For the two head and neck patient cases, the average clinical target volume (CTV) dose homogeneity index (V95%–V107%) over all the considered setup error scenarios was on average 19% lower for the PTV-based plans and it had a larger standard deviation. The robust-optimized plans achieved, on average, a 20% reduction in the OAR doses compared to the PTV-based plans. For the brain patient case, the CTV dose homogeneity index was similar for the two plans, while the OAR doses were 22% lower, on average, for the robust-optimized plan. No clear trend in terms of electron contributions was found across the three patient cases, although robust-optimized plans tended toward higher electron beam energies. Conclusions A framework for robust optimization of deliverable MBRT plans has been developed and validated. PTV-based MBRT were found to not be robust to setup errors, while the dose delivered by the robust-optimized plans were clinically acceptable for all considered error scenarios and had better OAR sparing. This study shows that the robust optimization is a promising alternative to conventional PTV margins for MBRT., Medical Physics, 48 (11), ISSN:0094-2405, ISSN:2473-4209, ISSN:1522-8541

Highlight • Dosimetric study suggests cognition sparing optimization with PBS-PT > IMRT > VMAT. • If available, PBS-PT is recommended for WV-RT in intracranial germ cell tumors. • IMRT is dosimetrically superior than VMAT regarding neurofunctional OAR sparing., Background Whole-ventricular radiotherapy (WV-RT) followed by a boost to the tumor bed (WV-RT/TB) is recommended for intracranial germ cell tumors (IGCT). As the critical brain areas are mainly in the target volume vicinity, it is unclear if protons indeed substantially spare neurofunctional organs at risk (NOAR). Therefore, a dosimetric comparison study of WV-RT/TB was conducted to assess whether proton or photon radiotherapy achieves better NOAR sparing. Methods Eleven children with GCT received 24 Gy(RBE) WV-RT and a boost up to 40 Gy(RBE) in 25 fractions of 1.6 Gy(RBE) with pencil beam scanning proton therapy (PBS-PT). Intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) plans were generated for these patients. NOAR were delineated and treatment plans were compared for target volume coverage (TVC), homogeneity index (HI), inhomogeneity coefficient (IC) and (N)OAR sparing. Results TVC was comparable for all three modalities. Compared to IMRT and VMAT, PBS-PT showed statistically significant optimized IC, as well as dose reduction, among others, in mean and integral dose to the: normal brain (−35.2%, −32.7%; −35.2%, −33.0%, respectively), cerebellum (−53.7%, −33.1%; −53.6%, −32.7%) and right temporal lobe (−14.5%, −31.9%; −14.7%, −29.9%). The Willis’ circle was better protected with PBS-PT than IMRT (−7.1%; −7.8%). The left hippocampus sparing was higher with IMRT. Compared to VMAT, the dose to the hippocampi, amygdalae and temporal lobes was significantly decreased in the IMRT plans. Conclusions Dosimetric comparison of WV-RT/TB in IGCT suggests PBS-PT's advantage over photons in conformality and NOAR sparing, whereas IMRT’s superiority over VMAT, thus potentially minimizing long-term sequelae.

Background Stereotactic radiosurgery (SRS) has been recognized as a first-line treatment option for small to moderate sized vestibular schwannoma (VS). Our aim is to evaluate the impact of SRS doses and other patient and disease characteristics on vestibular function in patients with VS. Methods Data on VS patients treated with single-fraction SRS to 12 Gy were retrospectively reviewed. No dose constraints were given to the vestibule during optimization in treatment planning. Patient and tumor characteristics, pre- and post-SRS vestibular examination results and patient-reported dizziness were assessed from patient records. Results Fifty-three patients were analyzed. Median follow-up was 32 months (range, 6–79). The median minimum, mean and maximum vestibular doses were 2.6 ± 1.6 Gy, 6.7 ± 2.8 Gy, and 11 ± 3.6 Gy, respectively. On univariate analysis, Koos grade (p = 0.04; OR: 3.45; 95% CI 1.01–11.81), tumor volume (median 6.1 cm3; range, 0.8–38; p = 0.01; OR: 4.85; 95% CI 1.43–16.49), presence of pre-SRS dizziness (p = 0.02; OR: 3.98; 95% CI 1.19–13.24) and minimum vestibular dose (p = 0.033; OR: 1.55; 95% CI 1.03–2.32) showed a significant association with patient-reported dizziness. On multivariate analysis, minimum vestibular dose remained significant (p = 0.02; OR: 1.75; 95% CI 1.05–2.89). Patients with improved caloric function had received significantly lower mean (1.5 ± 0.7 Gy, p = 0.01) and maximum doses (4 ± 1.5 Gy, p = 0.01) to the vestibule. Conclusions Our results reveal that 5 Gy and above minimum vestibular doses significantly worsened dizziness. Additionally, mean and maximum doses received by the vestibule were significantly lower in patients who had improved caloric function. Further investigations are needed to determine dose-volume parameters and their effects on vestibular toxicity.

Background Fully automatic medical image segmentation has been a long pursuit in radiotherapy (RT). Recent developments involving deep learning show promising results yielding consistent and time efficient contours. In order to train and validate these systems, several geometric based metrics, such as Dice Similarity Coefficient (DSC), Hausdorff, and other related metrics are currently the standard in automated medical image segmentation challenges. However, the relevance of these metrics in RT is questionable. The quality of automated segmentation results needs to reflect clinical relevant treatment outcomes, such as dosimetry and related tumor control and toxicity. In this study, we present results investigating the correlation between popular geometric segmentation metrics and dose parameters for Organs-At-Risk (OAR) in brain tumor patients, and investigate properties that might be predictive for dose changes in brain radiotherapy. Methods A retrospective database of glioblastoma multiforme patients was stratified for planning difficulty, from which 12 cases were selected and reference sets of OARs and radiation targets were defined. In order to assess the relation between segmentation quality -as measured by standard segmentation assessment metrics- and quality of RT plans, clinically realistic, yet alternative contours for each OAR of the selected cases were obtained through three methods: (i) Manual contours by two additional human raters. (ii) Realistic manual manipulations of reference contours. (iii) Through deep learning based segmentation results. On the reference structure set a reference plan was generated that was re-optimized for each corresponding alternative contour set. The correlation between segmentation metrics, and dosimetric changes was obtained and analyzed for each OAR, by means of the mean dose and maximum dose to 1% of the volume (Dmax 1%). Furthermore, we conducted specific experiments to investigate the dosimetric effect of alternative OAR contours with respect to the proximity to the target, size, particular shape and relative location to the target. Results We found a low correlation between the DSC, reflecting the alternative OAR contours, and dosimetric changes. The Pearson correlation coefficient between the mean OAR dose effect and the Dice was -0.11. For Dmax 1%, we found a correlation of -0.13. Similar low correlations were found for 22 other segmentation metrics. The organ based analysis showed that there is a better correlation for the larger OARs (i.e. brainstem and eyes) as for the smaller OARs (i.e. optic nerves and chiasm). Furthermore, we found that proximity to the target does not make contour variations more susceptible to the dose effect. However, the direction of the contour variation with respect to the relative location of the target seems to have a strong correlation with the dose effect. Conclusions This study shows a low correlation between segmentation metrics and dosimetric changes for OARs in brain tumor patients. Results suggest that the current metrics for image segmentation in RT, as well as deep learning systems employing such metrics, need to be revisited towards clinically oriented metrics that better reflect how segmentation quality affects dose distribution and related tumor control and toxicity.

Purpose. To develop a novel treatment planning process (TPP) with simultaneous optimization of modulated photon, electron and proton beams for improved treatment plan quality in radiotherapy. Methods. A framework for fluence map optimization of Monte Carlo (MC) calculated beamlet dose distributions is developed to generate treatment plans consisting of photon, electron and spot scanning proton fields. Initially, in-house intensity modulated proton therapy (IMPT) plans are compared to proton plans created by a commercial treatment planning system (TPS). A triple beam radiotherapy (TriB-RT) plan is generated for an exemplary academic case and the dose contributions of the three particle types are investigated. To investigate the dosimetric potential, a TriB-RT plan is compared to an in-house IMPT plan for two clinically motivated cases. Benefits of TriB-RT for a fixed proton beam line with a single proton field are investigated. Results. In-house optimized IMPT are of at least equal or better quality than TPS-generated proton plans, and MC-based optimization shows dosimetric advantages for inhomogeneous situations. Concerning TriB-RT, for the academic case, the resulting plan shows substantial contribution of all particle types. For the clinically motivated case, improved sparing of organs at risk close to the target volume is achieved compared to IMPT (e.g. myelon and brainstem D m a x −37%) at cost of an increased low dose bath (healthy tissue V 10% +22%). In the scenario of a fixed proton beam line, TriB-RT plans are able to compensate the loss in degrees of freedom to substantially improve plan quality compared to a single field proton plan. Conclusion. A novel TPP which simultaneously optimizes photon, electron and proton beams was successfully developed. TriB-RT shows the potential for improved treatment plan quality and is especially promising for cost-effective single-room proton solutions with a fixed beamline in combination with a conventional linac delivering photon and electron fields.

Background Automated brain tumor segmentation methods are computational algorithms that yield tumor delineation from, in this case, multimodal magnetic resonance imaging (MRI). We present an automated segmentation method and its results for resection cavity (RC) in glioblastoma multiforme (GBM) patients using deep learning (DL) technologies. Methods Post-operative, T1w with and without contrast, T2w and fluid attenuated inversion recovery MRI studies of 30 GBM patients were included. Three radiation oncologists manually delineated the RC to obtain a reference segmentation. We developed a DL cavity segmentation method, which utilizes all four MRI sequences and the reference segmentation to learn to perform RC delineations. We evaluated the segmentation method in terms of Dice coefficient (DC) and estimated volume measurements. Results Median DC of the three radiation oncologist were 0.85 (interquartile range [IQR]: 0.08), 0.84 (IQR: 0.07), and 0.86 (IQR: 0.07). The results of the automatic segmentation compared to the three different raters were 0.83 (IQR: 0.14), 0.81 (IQR: 0.12), and 0.81 (IQR: 0.13) which was significantly lower compared to the DC among raters (chi-square = 11.63, p = 0.04). We did not detect a statistically significant difference of the measured RC volumes for the different raters and the automated method (Kruskal-Wallis test: chi-square = 1.46, p = 0.69). The main sources of error were due to signal inhomogeneity and similar intensity patterns between cavity and brain tissues. Conclusions The proposed DL approach yields promising results for automated RC segmentation in this proof of concept study. Compared to human experts, the DC are still subpar.

Purpose: In the current era of MRI-linac radiotherapy, dose optimization with arbitrary dose distributions is a reality. For the first time, we present new and targeted experiments and modeling to aid in evaluating the potential dose improvements offered with an electron beam mode during MRI-linac radiotherapy. Methods: Small collimated (1 cm diameter and 1.5 × 1.5 cm2 square) electron beams (6, 12 and 20 MeV) from a clinical linear accelerator (Varian Clinac 2100C) are incident perpendicular and parallel to the strong and localized magnetic fields (0–0.7 T) generated by a permanent magnet device. Gafchromic EBT3 film is placed inside a slab phantom to measure two-dimensional dose distributions. A benchmarked and comprehensive Monte Carlo model (Geant4) is established to directly compare with experiments. Results: With perpendicular fields a 5% narrowing of the beam FWHM and a 10 mm reduction in the 15% isodose penetration is seen for the 20 MeV beam. In the inline setup the penumbral width is reduced by up to 20%, and a local central dose enhancement of 100% is observed. Monte Carlo simulations are in agreement with the measured dose distributions (2% or 2 mm). Conclusion: A new range of experiments have been performed to offer insight into how an electron beam mode could offer additional choices in MRI-linac radiotherapy. The work extends on historic studies to bring a successful unified experimental and Monte Carlo modeling approach for studying small field electron beam dosimetry inside magnetic fields. The results suggest further work, particularly on the inline magnetic field scenario. © 2020 Associazione Italiana di Fisica Medica, Physica Medica, 78, ISSN:1120-1797, ISSN:1724-191X

Micro computed tomography (µCT) scanners are used to create high-resolution images and to quantify properties of the scanned objects. While modern µCT scanners benefit from the cone beam geometry, they are compromised by scatter radiation. This work aims to develop a Monte Carlo (MC) model of a µCT scanner in order to characterize the scatter radiation in the detector plane. The EGS++ framework with the MC code EGSnrc was used to simulate the particle transport through the main components of the XtremeCT (SCANCO Medical AG, Switzerland). The developed MC model was based on specific information of the manufacturer and was validated against measurements. The primary and the scatter radiation were analyzed and by implementing a dedicated tracing method, the scatter radiation was subdivided into different scatter components. The comparisons of measured and simulated transmission values for different absorber and filter combinations result in a mean difference of 0.2% ± 1.4%, with a maximal local difference of 3.4%. The reconstructed image of the phantom based on measurements agrees well with the image reconstructed using the MC model. The local contribution of scattered radiation is up to 10% of the total radiation in the detector plane and most of the scattered particles result from interactions in the scanned object. The MC simulations show that scatter radiation contains information about the structure of the object. In conclusion, a MC model for a µCT scanner was successfully validated and applied to analyze the characteristics of the scatter radiation for a µCT scanner.

The aim of this work is to develop and investigate an inverse treatment planning process (TPP) for mixed beam radiotherapy (MBRT) capable of performing simultaneous optimization of photon and electron apertures. A simulated annealing based direct aperture optimization (DAO) is implemented to perform simultaneous optimization of photon and electron apertures, both shaped with the photon multileaf collimator (pMLC). Validated beam models are used as input for Monte Carlo dose calculations. Consideration of photon pMLC transmission during DAO and a weight re-optimization of the apertures after deliverable dose calculation are utilized to efficiently reduce the differences between optimized and deliverable dose distributions. The TPP for MBRT is evaluated for an academic situation with a superficial and an enlarged PTV in the depth, a left chest wall case including the internal mammary chain and a squamous cell carcinoma case. Deliverable dose distributions of MBRT plans are compared to those of modulated electron radiotherapy (MERT), photon IMRT and if available to those of clinical VMAT plans. The generated MBRT plans dosimetrically outperform the MERT, photon IMRT and VMAT plans for all investigated situations. For the clinical cases of the left chest wall and the squamous cell carcinoma, the MBRT plans cover the PTV similarly or more homogeneously than the VMAT plans, while OARs are spared considerably better with average reductions of the mean dose to parallel OARs and D 2% to serial OARs by 54% and 26%, respectively. Moreover, the low dose bath expressed as V 10% to normal tissue is substantially reduced by up to 45% compared to the VMAT plans. A TPP for MBRT including simultaneous optimization is successfully implemented and the dosimetric superiority of MBRT plans over MERT, photon IMRT and VMAT plans is demonstrated for academic and clinical situations including superficial targets with and without deep-seated part.

Purpose To provide fast and accurate dose calculation in voxelized geometries for proton radiation therapy by implementing an adaptive step size algorithm in the proton macro Monte Carlo (pMMC) method. Methods The in-house developed local-to-global MMC method for proton dose calculation is extended with an adaptive step size algorithm for efficient proton transport through a voxelized geometry by sampling transport parameters from a pre-simulated database. Adaptive choice of an adequate slab size in dependence of material interfaces in the proton’s longitudinal and lateral vicinity is investigated. The dose calculation algorithm is validated against the non-adaptive pMMC and full MC simulation for pencil and broad beams with various energies impinging on academic phantoms as well as a head and neck patient CT. Results For material interfaces perpendicular to a proton’s direction, choice of nearest neighbor slab thickness shows best trade-off between dosimetric accuracy and calculation efficiency. Adaptive reduction of chosen slab size is shown to be required for material interfaces closer than 0.5 mm in lateral direction. For the academic phantoms, dose differences of within 1% or 1 mm compared to full Geant4 MC simulation are found, while achieving an efficiency gain of up to a factor of 5.6 compared to the non-adaptive algorithm and 284 compared to Geant4. For the head and neck patient CT, dose differences are within 1% or 1 mm with an efficiency gain factor of up to 3.4 compared to the non-adaptive algorithm and 145 compared to Geant4. Conclusion An adaptive step size algorithm for proton macro Monte Carlo was implemented and evaluated. The dose calculation provides the accuracy of full MC simulations, while achieving an efficiency gain factor of three compared to the non-adaptive algorithm and two orders of magnitude compared to full MC for a complex patient CT., Radiation Oncology, 14 (1)

Background Vendor-independent Monte Carlo (MC) dose calculation (IDC) for patient-specific quality assurance of multi-leaf collimator (MLC) based CyberKnife treatments is used to benchmark and validate the commercial MC dose calculation engine for MLC based treatments built into the CyberKnife treatment planning system (Precision MC). Methods The benchmark included dose profiles in water in 15 mm depth and depth dose curves of rectangular MLC shaped fields ranging from 7.6 mm × 7.7 mm to 115.0 mm × 100.1 mm, which were compared between IDC, Precision MC and measurements in terms of dose difference and distance to agreement. Dose distributions of three phantom cases and seven clinical lung cases were calculated using both IDC and Precision MC. The lung PTVs ranged from 14 cm3 to 93 cm3. Quantitative comparison of these dose distributions was performed using dose-volume parameters and 3D gamma analysis with 2% global dose difference and 1 mm distance criteria and a global 10% dose threshold. Time to calculate dose distributions was recorded and efficiency was assessed. Results Absolute dose profiles in 15 mm depth in water showed agreement between Precision MC and IDC within 3.1% or 1 mm. Depth dose curves agreed within 2.3% / 1 mm. For the phantom and clinical lung cases, mean PTV doses differed from − 1.0 to + 2.3% between IDC and Precision MC and gamma passing rates were > =98.1% for all multiple beam treatment plans. For the lung cases, lung V20 agreed within ±1.5%. Calculation times ranged from 2.2 min (for 39 cm3 PTV at 1.0 × 1.0 × 2.5 mm3 native CT resolution) to 8.1 min (93 cm3 at 1.1 × 1.1 × 1.0 mm3), at 2% uncertainty for Precision MC for the 7 examined lung cases and 4–6 h for IDC, which, however, is not optimized for efficiency but used as a gold standard for accuracy. Conclusions Both accuracy and efficiency of Precision MC in the context of MLC based planning for the CyberKnife M6 system were benchmarked against MC based IDC framework. Precision MC is used in clinical practice at our institute.

Dose rate is an essential factor in radiobiology. As modern radiotherapy delivery techniques such as volumetric modulated arc therapy (VMAT) introduce dynamic modulation of the dose rate, it is important to assess the changes in dose rate. Both the rate of monitor units per minute (MU rate) and collimation are varied over the course of a fraction, leading to different dose rates in every voxel of the calculation volume at any point in time during dose delivery. Given the radiotherapy plan and machine specific limitations, a VMAT treatment plan can be split into arc sectors between Digital Imaging and Communications in Medicine control points (CPs) of constant and known MU rate. By calculating dose distributions in each of these arc sectors independently and multiplying them with the MU rate, the dose rate in every single voxel at every time point during the fraction can be calculated. Independently calculated and then summed dose distributions per arc sector were compared to the whole arc dose calculation for validation. Dose measurements and video analysis were performed to validate the calculated datasets. A clinical head and neck, cranial and liver case were analyzed using the tool developed. Measurement validation of synthetic test cases showed linac agreement to precalculated arc sector times within ±0.4 s and doses ±0.1 MU (one standard deviation). Two methods for the visualization of dose rate datasets were developed: the first method plots a two-dimensional (2D) histogram of the number of voxels receiving a given dose rate over the course of the arc treatment delivery. In similarity to treatment planning system display of dose, the second method displays the dose rate as color wash on top of the corresponding computed tomography image, allowing the user to scroll through the variation over time. Examining clinical cases showed dose rates spread over a continuous spectrum, with mean dose rates hardly exceeding 100 cGy min(-1) for conventional fractionation. A tool to analyze dose rate distributions in VMAT plans with sub-second accuracy was successfully developed and validated. Dose rates encountered in clinical VMAT test cases show a continuous spectrum with a mean less than or near 100 cGy min(-1) for conventional fractionation.

OBJECTIVE In this study, the "Progressive Resolution Optimizer PRO3" (Varian Medical Systems) is compared to the previous version "PRO2" with respect to its potential to improve dose sparing to the organs at risk (OAR) and dose coverage of the PTV for head and neck cancer patients. MATERIALS AND METHODS For eight head and neck cancer patients, volumetric modulated arc therapy (VMAT) treatment plans were generated in this study. All cases have 2-3 phases and the total prescribed dose (PD) was 60-72Gy in the PTV. The study is mainly focused on the phase 1 plans, which all have an identical PD of 54Gy, and complex PTV structures with an overlap to the parotids. Optimization was performed based on planning objectives for the PTV according to ICRU83, and with minimal dose to spinal cord, and parotids outside PTV. In order to assess the quality of the optimization algorithms, an identical set of constraints was used for both, PRO2 and PRO3. The resulting treatment plans were investigated with respect to dose distribution based on the analysis of the dose volume histograms. RESULTS For the phase 1 plans (PD=54Gy) the near maximum dose D2% of the spinal cord, could be minimized to 22±5 Gy with PRO3, as compared to 32±12Gy with PRO2, averaged for all patients. The mean dose to the parotids was also lower in PRO3 plans compared to PRO2, but the differences were less pronounced. A PTV coverage of V95%=97±1% could be reached with PRO3, as compared to 86±5% with PRO2. In clinical routine, these PRO2 plans would require modifications to obtain better PTV coverage at the cost of higher OAR doses. CONCLUSION A comparison between PRO3 and PRO2 optimization algorithms was performed for eight head and neck cancer patients. In general, the quality of VMAT plans for head and neck patients are improved with PRO3 as compared to PRO2. The dose to OARs can be reduced significantly, especially for the spinal cord. These reductions are achieved with better PTV coverage as compared to PRO2. The improved spinal cord sparing offers new opportunities for all types of paraspinal tumors and for re-irradiation of recurrent tumors or second malignancies., Zielsetzung In dieser Studie wird der „Progressive Resolution Optimizer PRO3“ (Varian Medical Systems) mit der Vorgängerversion „PRO2“ gezielt auf sein Potential bei Kopf-Hals-Tumoren untersucht. Im Vordergrund stehen die Dosisabdeckung des PTV und die Schonung der Risikoorgane (OAR). Methoden Für acht Patienten wurden VMAT-Pläne mit beiden Algorithmen erstellt. Die Gesamtdosis im PTV von 60-72 Gy ist in allen Fällen auf 2-3 Phasen verteilt, die nacheinander abgestrahlt werden. Die Studie ist fokussiert auf die erste Bestrahlungsphase, die in allen Fällen eine komplexe PTV-Struktur mit Planungsdosis von 54 Gy hatte und teilweise mit den Parotiden überlappte. Grundlage für die Optimierung sind die ICRU83-Richtlinien für das PTV und das Planungsziel, das Rückenmark und die Parotiden außerhalb des PTV maximal zu schonen. In einem ersten Schritt wurde durch interaktive Planung mit PRO3 ein möglichst optimaler Plan generiert. Die dabei gewählten Grenzwerte („dose constraints“) für PTV und Risikoorgane wurden in einem zweiten Schritt für den Vergleich der Optimierungsalgorithmen verwendet. Die Optimierung wurde also für diese nun fest vorgegebenen Dosisgrenzwerte sowohl mit PRO3 wiederholt als auch mit PRO2 durchgeführt, ohne zusätzliche Interaktion des Planers. Die resultierenden beiden Bestrahlungspläne wurden anhand der Dosis-Volumen-Histogramme verglichen. Ergebnisse Ein markanter Unterschied in Planqualität ergibt sich aus dem Vergleich der Rückenmarkdosis in der ersten Bestrahlungsphase mit 54 Gy Dosis im PTV. Die maximum-nahe Dosis D2% im Rückenmark konnte mit PRO3 auf 22±5 Gy reduziert werden, während die Optimierung mit identischen Randbedingungen bei PRO2 eine Dosis D2% von 32±12 Gy ergab. Auch die mittlere Dosis für die Parotiden war kleiner mit PRO3, allerdings mit einem weniger großen Unterschied. Eine PTV-Abdeckung von V95% = 97±1% konnte mit PRO3 erreicht werden. Mit PRO2 lag diese Abdeckung dagegen nur bei V95% = 86±5%. Die Mehrzahl der so generierten PRO2-Pläne würde in klinischer Routine nicht akzeptiert und müsste durch die Anpassung der Randbedingungen modifiziert werden, so dass die Dosis auf die Risikoorgane entsprechend höher wird. Schlussfolgerung Ein Vergleich der Optimierungsalgorithmen PRO2 und PRO3 wurde bei acht Patienten mit Kopf-Hals-Tumoren durchgeführt. Hierbei wurde mit dem Algorithmus PRO3 eine deutlich bessere Planqualität erzielt als mit PRO2. Die Verbesserung führt zu einer tieferen Belastung der Risikoorgane, mit dem deutlichsten Unterschied beim Rückenmark. Diese Schonung geht nicht zu Lasten der PTV-Abdeckung. Vielmehr wurde bei allen PRO3-Plänen eine bessere PTV-Abdeckung erzielt als mit PRO2. Die verbesserte Möglichkeit der Rückenmarkschonung, auch für komplexe PTV, eröffnet neue Möglichkeiten der Bestrahlung paraspinaler Tumore. Durch die Schonung des Rückenmarks ist zudem eine erneute Bestrahlung bei wiederauftretenden Tumoren möglich.

PURPOSE The purpose of this study was to develop a treatment technique for dynamic mixed beam radiotherapy (DYMBER) utilizing increased degrees of freedom (DoF) of a conventional treatment unit including different particle types (photons and electrons), intensity and energy modulation and dynamic gantry, table, and collimator rotations. METHODS A treatment planning process has been developed to create DYMBER plans combining photon dynamic trajectories (DTs) and step and shoot electron apertures collimated with the photon multileaf collimator (pMLC). A gantry-table path is determined for the photon DTs with minimized overlap of the organs at risk (OARs) with the target. In addition, an associated dynamic collimator rotation is established with minimized area between the pMLC leaves and the target contour. pMLC sequences of photon DTs and electron pMLC apertures are then simultaneously optimized using direct aperture optimization (DAO). Subsequently, the final dose distribution of the electron pMLC apertures is calculated using the Swiss Monte Carlo Plan (SMCP). The pMLC sequences of the photon DTs are then re-optimized with a finer control point resolution and with the final electron dose distribution taken into account. Afterwards, the final photon dose distribution is calculated also using the SMCP and summed together with the one of the electrons. This process is applied for a brain and two head and neck cases. The resulting DYMBER dose distributions are compared to those of dynamic trajectory radiotherapy (DTRT) plans consisting only of photon DTs and clinically applied VMAT plans. Furthermore, the deliverability of the DYMBER plans is verified in terms of dosimetric accuracy, delivery time and collision avoidance. For this purpose, The DYMBER plans are delivered to Gafchromic EBT3 films placed in an anthropomorphic head phantom on a Varian TrueBeam linear accelerator. RESULTS For each case, the dose homogeneity in the target is similar or better for DYMBER compared to DTRT and VMAT. Averaged over all three cases, the mean dose to the parallel OARs is 16% and 28% lower, D to the serial OARs is 17% and 37% lower and V to normal tissue is 12% and 4% lower for the DYMBER plans compared to the DTRT and VMAT plans, respectively. The DYMBER plans are delivered without collision and with a 4-5 min longer delivery time than the VMAT plans. The absolute dose measurements are compared to calculation by gamma analysis using 2% (global)/2 mm criteria with passing rates of at least 99%. CONCLUSIONS A treatment technique for DYMBER has been successfully developed and verified for its deliverability. The dosimetric superiority of DYMBER over DTRT and VMAT indicates utilizing increased DoF to be the key to improve brain and head and neck radiation treatments in future.

For patients with inoperable liver metastases, intra-operative liver high dose-rate brachytherapy (HDR-BT) is a promising technology enabling delivery of a high radiation dose to the tumor, while sparing healthy tissue. Liver brachytherapy has been described in the literature as safe and effective for the treatment of primary or secondary hepatic malignancies. It is preferred over other ablative techniques for lesions that are either larger than 4 cm or located in close proximity to large vessels or the common bile duct. In contrast to external beam radiation techniques, organ movements do not affect the size of the irradiated volume in intra-operative HDR-BT and new technical solutions exist to support image guidance for intra-operative HDR-BT. We have retrospectively analyzed anonymized CT datasets of 5 patients who underwent open liver surgery (resection and/or ablation) in order to test whether the accuracy of a new image-guidance method specifically adapted for intra-operative HDR-BT is high enough to use it in similar situations and whether patients could potentially benefit from navigation-guided intra-operative needle placement for liver HDR-BT.

Compared to a conventional linear accelerator, the Cyberknife (CK) is a unique system with respect to radiation protection shielding and the variety and number of non-coplanar beams are two key components regarding this aspect. In this work, a framework to assess the direction distribution and modulation factor (MF) of clinically applied treatment beams of a CyberKnife M6 is developed. Database filtering options allow studying the influence of different parameters such as collimator types, treatment sites or different bunker sizes. A distribution of monitor units (MU) is generated by projecting treatment beams onto the walls, floor and ceiling of the CyberKnife bunker. This distribution is found to be highly heterogeneous and depending, among other parameters, on the bunker size. For our bunker design, 10%–13% of the MUs are delivered to the right and left wall, each. The floor receives more than 64% of the applied MUs, while the wall behind the patient's head is not hit by primary treatment beams. Between 0% and 5% of the total MUs are delivered to the wall at the patient's feet. This number highly depends on the treatment site, e.g., for extracranial patients no beams hit that wall. Collimator choice was found to have minor influence on the distribution of MUs. On the other hand, the MF depends on the collimator type as well as on the treatment site. The MFs (delivered MU/prescribed dose) for all treatments, all MLC treatments, cranial and extracranial treatments are 8.3, 6.4, 7.7, and 9.9 MU/cGy, respectively. The developed framework allows assessing and monitoring important parameters regarding radiation protection of a CK-M6 using the actually applied treatment beams. Furthermore, it enables evaluating different clinical and constructional situations using the filtering options., Journal of Applied Clinical Medical Physics, 19 (1), ISSN:1526-9914

The impact of several physical quantities on the spatial resolution of an X-ray scintillating pixel detector for a micro cone beam CT (µCBCT) is investigated and discussed. The XtremeCT from SCANCO Medical AG was simulated using the EGSnrc/EGS++ Monte Carlo (MC) framework and extensively benchmarked in a previous work. The resolution of the detector was determined by simulating a titanium knife-edge to obtain the edge spread function (ESF) and the modulation transfer function (MTF). Propagation of the scintillation light through the scintillator and its coupling into the fiber optics system was taken into account. The contribution of particles scattered in the main scanner components to the detector signal is very low and does not affect the spatial resolution of the detector. The resolution obtained from the energy deposition in the scintillator without any blurring due to the propagation of the scintillation light into the fiber optics array was 31 µm. By assuming isotropic light propagation in the scintillator, the resolution degraded to 360 µm. A simple light propagation model taking into account the impact of the scintillator's columnar microstructures was developed and compared with the MANTIS Monte Carlo simulation package. By reducing the width of the model's light propagation kernel by a factor of 2 compared to the isotropic case, the detector resolution can be improved to 83 µm, which corresponds well to the measured resolution of 86 µm. The resolution of the detector is limited mainly by the propagation of the scintillation light through the scintillator layer. It offers the greatest potential to improve the resolution of the µCBCT imaging system.

This work aims to develop, implement and validate a Monte Carlo (MC)-based independent dose calculation (IDC) framework to perform patient-specific quality assurance (QA) for multi-leaf collimator (MLC)-based CyberKnife® (Accuray Inc., Sunnyvale, CA) treatment plans. The IDC framework uses an XML-format treatment plan as exported from the treatment planning system (TPS) and DICOM format patient CT data, an MC beam model using phase spaces, CyberKnife MLC beam modifier transport using the EGS++ class library, a beam sampling and coordinate transformation engine and dose scoring using DOSXYZnrc. The framework is validated against dose profiles and depth dose curves of single beams with varying field sizes in a water tank in units of cGy/Monitor Unit and against a 2D dose distribution of a full prostate treatment plan measured with Gafchromic EBT3 (Ashland Advanced Materials, Bridgewater, NJ) film in a homogeneous water-equivalent slab phantom. The film measurement is compared to IDC results by gamma analysis using 2% (global)/2 mm criteria. Further, the dose distribution of the clinical treatment plan in the patient CT is compared to TPS calculation by gamma analysis using the same criteria. Dose profiles from IDC calculation in a homogeneous water phantom agree within 2.3% of the global max dose or 1 mm distance to agreement to measurements for all except the smallest field size. Comparing the film measurement to calculated dose, 99.9% of all voxels pass gamma analysis, comparing dose calculated by the IDC framework to TPS calculated dose for the clinical prostate plan shows 99.0% passing rate. IDC calculated dose is found to be up to 5.6% lower than dose calculated by the TPS in this case near metal fiducial markers. An MC-based modular IDC framework was successfully developed, implemented and validated against measurements and is now available to perform patient-specific QA by IDC.

Standard electron treatments are currently still performed using standard or molded patient-specific cut-outs placed in the electron applicator. Replacing cut-outs and electron applicators with a photon multileaf collimator (pMLC) for electron beam collimation would make standard electron treatments more efficient and would facilitate advanced treatment techniques like modulated electron radiotherapy (MERT) and mixed beam radiotherapy (MBRT). In this work, a multiple source Monte Carlo beam model for pMLC shaped electron beams commissioned at a source-to-surface distance (SSD) of 70 cm is extended for SSDs of up to 100 cm and validated for several Varian treatment units with field sizes typically used for standard electron treatments. Measurements and dose calculations agree generally within 3% of the maximal dose or 2 mm distance to agreement. To evaluate the dosimetric consequences of using pMLC collimated electron beams for standard electron treatments, pMLC-based and cut-out-based treatment plans are created for a left and a right breast boost, a sternum, a testis and a parotid gland case. The treatment plans consist of a single electron field, either alone (1E) or in combination with two 3D conformal tangential photon fields (1E2X). For each case, a pMLC plan with similar treatment plan quality in terms of dose homogeneity to the target and absolute mean dose values to the organs at risk (OARs) compared to a cut-out plan is found. The absolute mean dose to an OAR is slightly increased for pMLC-based compared to cut-out-based 1E plans if the OAR is located laterally close to the target with respect to beam direction, or if a 6 MeV electron beam is used at an extended SSD. In conclusion, treatment plans using cut-out collimation can be replaced by plans of similar treatment plan quality using pMLC collimation with accurately calculated dose distributions.

Purpose: Advanced radiation therapy requires highly sophisticated dose calculation algorithms such as finite element based Boltzmann solvers or Monte Carlo(MC) methods. MC is commonly accepted as the golden standard method for dose calculation in high energy treatments and thus it is used for benchmarking other algorithms. In this work the quality of dose distribution calculated using the Boltzmann solver based AcurosXB algorithm within Eclipse (Varian Medical Systems) is investigated for volumetric modulated arc treatment (VMAT) plans involving the high definition MLC (HD120 MLC) by comparing doses with the validated Swiss Monte Carlo Plan (SMCP).Materials & Methods: Within SMCP and Eclipse using AcurosXB, 10 VMAT H&N patient plans and corresponding verification plans were recalculated using fixed MUs. In SMCP, radiation transport and dose calculation were performed using VMC++ with a statistical uncertainty of 1%. The voxel size was 2.5 mm for SMCP and AcurosXB and the same material composition data was used for CT conversion. Dose volume histograms (DVH) were used in order to quantify the difference between the dose distributions of the patient plans. In addition, calculated verification plans were compared with measurements carried out with the Delta4 system (Scandidos) by using the gamma evaluation with 3%/3 mm criteria of points having a dose larger than 20% of isocenter dose.Results: DVHs for the patient plans showed good agreement between SMCP and AcurosXB calculations. Overall AcurosXB lead to an underestimation of the median dose values by about 1%. For measured total dose distributions of the verification plans on average 98.6% and 99.0% of the points fullfil the gamma criteria for the dose calculated using AcurosXB and SMCP, respectively. Conclusions: Resulting AcurosXB dose distributions for VMAT H&N plans involving a HD120 MLC are in good agreement with calculated SMCP dose distributions. Conflict of Interest: This work was supported by Varian Medical Systems

Purpose: Micro CBCTscanners have a broad spectrum of applications in medicine and material science. However, CBCT suffers from scatter radiation and spectral effects such as beam hardening (BH). In this work an iterative BH‐ and scatter‐correction algorithm was developed using Monte Carlo(MC) methods. Methods: Two μCBCT scannermodels (XtremeCT and μCT100 from SCANCO Medical AG) were simulated using EGSnrc/EGS++. The scanner measures the attenuation of X‐rays passing through the phantom and interacting in a scintillating detector. The MC method is used to characterize the influence of the scattering and BH‐ effects. In addition, an analytical model is developed in order to correct for the scattering effect. For this purpose, by using MC methods, different scatter components were analyzed with respect to the number of scatter interactions within the given geometry. For the BH‐effect, after assessing the detector response for an equivalent mono‐energetic and scatter‐free system using MC methods, an analytical correction model was developed. Both correction methods were implemented as an iterative reconstruction correction algorithm and were tested for various phantoms. Results:MC simulations show that the amounts of correction for the scattering and BH‐ effects are in the same order of magnitude. The correction term for scattering effects is a function of the scatter to primary ratio only and is mainly due to single scattered particles. The contribution of multiple scattered particles to the total scatter signal is small and can be approximated by a constant. In all cases tested, the reconstructed linear attenuation coefficients converge to the mono‐energetic reference values after 2–3 iteration steps with a deviation of about 1%. Conclusions: By using an iterative correction algorithm using single scatter approximation, BH‐ and scatter correction can be performed accurately for μCBCT scanners. This work was supported by CTI‐10629.1 and SCANCO Medical AG.

Purpose Most dose calculations for HDR brachytherapy treatments are based on the AAPM-TG43 formalism. Because patient's anatomy, heterogeneities and applicator shielding are not considered, the dose calculation based on this formalism is inaccurate in some cases. Alternatively, Collapsed Cone (CC) methods as well as Monte Carlo (MC) algorithms belong to the model based dose calculation algorithms, which are expected to improve the accuracy of calculated dose distributions. In this work, the performance of a CC algorithm, ACE in Oncentra Brachy 4.5 (ACE 4.5), has been investigated by comparing the calculated dose distributions to the AAPM-TG43 and MC calculations for 10 HDR brachytherapy accelerated partial breast irradiation treatments (APBI). Comparisons were also performed with a corrected version of ACE 4.5 (ACE 4.5/corr). Methods The brachytherapy source microSelectron mHDR-v2 (Elekta Brachytherapy) has been implemented in a MC environment and validated by comparing MC dose distributions simulated in a water phantom of 80 cm in diameter with dose distributions calculated with the AAPM-TG43 algorithm. Dose distributions calculated with ACE 4.5, ACE 4.5/corr, AAPM-TG43 formalism and MC for 10 APBI patients plans have then been computed and compared using HU scaled densities. In addition, individual dose components have been computed using ACE 4.5, ACE 4.5/corr and MC and compared individually. Results Local differences between MC and AAPM-TG43 calculated dose distributions in a large water phantom are

Background The aim was to evaluate the geometric and corresponding dosimetric differences between two delineation strategies for head and neck tumors neighboring air cavities. Methods Primary gross and clinical tumor volumes (GTV and CTV) of 14 patients with oropharynx or larynx tumors were contoured using a soft tissue window (S). In a second strategy, the same volumes were contoured with an extension to include the parts which became visible on lung window (L). For the calculation of Hausdorff-distances (HD) between contoured volumes of the two strategies, triangular meshes were exported. Two radiotherapy plans with identical goals and optimization parameters were generated for each case. Plan_S were optimized on CTV_S, and Plan_L on CTV_L. The dose coverages of CTV_L and CTV_Δ (CTV_L minus CTV_S) were evaluated in Plan_S. OAR doses were compared among Plan_S and Plan_L. Results Median three-dimensional HD for GTVs and CTVs were 5.7 (±2.6) and 9.3 (±2.8) mm, respectively. The median volume differences between structures contoured using L and S windows were 9% (±5%) and 9% (±4%) for GTV and CTV, respectively. In 13 out of 14 cases, Plan_S met the plan acceptance criteria for CTV_L. In 8 cases CTV_Δ was covered insufficiently in Plan_S. Mean and median differences in OAR dose-volume histogram parameters between Plan_S and Plan_L were within 3%. Conclusion For the current practice in radiotherapy planning for head and neck cancer, the delineation of L-based volumes seems unnecessary. However, in special settings, where smaller or no PTV margins are used, this approach may play an important role for local control. Electronic supplementary material The online version of this article (doi:10.1186/s13014-017-0838-4) contains supplementary material, which is available to authorized users.

Purpose: The aim of this work was a Monte Carlo (MC) based investigation of the impact of different radiation transport methods in collimators of a linear accelerator on photon beam characteristics, dose distributions, and efficiency. Thereby it is investigated if it is possible to use different simplifications in the radiation transport for some clinical situations in order to save calculation time. Methods: Within the Swiss Monte Carlo Plan, a GUI-based framework for photon MC treatment planning, different MC methods are available for the radiation transport through the collimators [secondary jaws and multileaf collimator (MLC)]: EGSnrc (reference), VMC++, and Pin (an in-house developed MC code). Additional nonfull transport methods were implemented in order to provide different complexity levels for the MC simulation: Considering collimator attenuation only, considering Compton scatter only or just the firstCompton process, and considering the collimators as totally absorbing. Furthermore, either a simple or an exact geometry of the collimators can be selected for the absorbing or attenuation method. Phasespaces directly above and dose distributions in a water phantom are analyzed for academic and clinical treatment fields using 6 and 15 MV beams, including intensity modulated radiation therapy with dynamic MLC. Results: For all MC transport methods, differencesmore » in the radial mean energy and radial energy fluence are within 1% inside the geometric field. Below the collimators, the energy fluence is underestimated for nonfull MC transport methods ranging from 5% for Compton to 100% for Absorbing. Gamma analysis using EGSnrc calculated doses as reference shows that the percentage of voxels fulfilling a 1% /1 mm criterion is at least 98% when using VMC++, Compton, or firstCompton transport methods. When using the methods Pin, Transmission, Flat-Transmission, Flat-Absorbing or Absorbing, the mean value of points fulfilling this criterion over all tested cases is 97%, 88%, 74%, 68%, or 65%, respectively. However, compared to EGSnrc calculations, the gain in efficiency is a factor of up to 10 for VMC++ and up to 48 for the absorbing method. Conclusions: The results of this investigation suggest that it is an option to use a simple transport technique in the initial treatment planning process and use more accurate transport methods for the final dose calculation accepting longer calculation times.« less

The aim of this work is to investigate to what extent it is possible to use the secondary collimator jaws to reduce the transmitted radiation through the multileaf collimator (MLC) during an intensity modulated radiation therapy (IMRT). A method is developed and introduced where the jaws follow the open window of the MLC dynamically (dJAW method). With the aid of three academic cases (Closed MLC, Sliding-gap, and Chair) and two clinical cases (prostate and head and neck) the feasibility of the dJAW method and the influence of this method on the applied dose distributions are investigated. For this purpose the treatment planning system Eclipse and the Research-Toolbox were used as well as measurements within a solid water phantom were performed. The transmitted radiation through the closed MLC leads to an inhomogeneous dose distribution. In this case, the measured dose within a plane perpendicular to the central axis differs up to 40% (referring to the maximum dose within this plane) for 6 and 15 MV. The calculated dose with Eclipse is clearly more homogeneous. For the Sliding-gap case this difference is still up to 9%. Among other things, these differences depend on the depth of the measurement within the solid water phantom and on the application method. In the Chair case, the dose in regions where no dose is desired is locally reduced by up to 50% using the dJAW method instead of the conventional method. The dose inside the chair-shaped region decreased up to 4% if the same number of monitor units (MU) as for the conventional method was applied. The undesired dose in the volume body minus the planning target volume in the clinical cases prostate and head and neck decreased up to 1.8% and 1.5%, while the number of the applied MU increased up to 3.1% and 2.8%, respectively. The new dJAW method has the potential to enhance the optimization of the conventional IMRT to a further step.

Describes the benefits of using robots to unload injection moulding machines and the various robot configurations that can be applied. The use of robots to assist in the manufacture of injection moulded loading doors for domestic washing machines is given as an example.

The electron Monte Carlo (eMC) dose calculation algorithm available in the Eclipse treatment planning system (Varian Medical Systems) is based on the macro MC method and uses a beam model applicable to Varian linear accelerators. This leads to limitations in accuracy if eMC is applied to non-Varian machines. In this work eMC is generalized to also allow accurate dose calculations for electron beams from Elekta and Siemens accelerators. First, changes made in the previous study to use eMC for low electron beam energies of Varian accelerators are applied. Then, a generalized beam model is developed using a main electron source and a main photon source representing electrons and photons from the scattering foil, respectively, an edge source of electrons, a transmission source of photons and a line source of electrons and photons representing the particles from the scrapers or inserts and head scatter radiation. Regarding the macro MC dose calculation algorithm, the transport code of the secondary particles is improved. The macro MC dose calculations are validated with corresponding dose calculations using EGSnrc in homogeneous and inhomogeneous phantoms. The validation of the generalized eMC is carried out by comparing calculated and measured dose distributions in water for Varian, Elekta and Siemens machines for a variety of beam energies, applicator sizes and SSDs. The comparisons are performed in units of cGy per MU. Overall, a general agreement between calculated and measured dose distributions for all machine types and all combinations of parameters investigated is found to be within 2% or 2 mm. The results of the dose comparisons suggest that the generalized eMC is now suitable to calculate dose distributions for Varian, Elekta and Siemens linear accelerators with sufficient accuracy in the range of the investigated combinations of beam energies, applicator sizes and SSDs.

Purpose The range of patient setup errors in six dimensions detected in clinical routine for cranial as well as for extracranial treatments, were analyzed while performing linear accelerator based stereotactic treatments with frameless patient setup systems. Additionally, the need for re-verification of the patient setup for situations where couch rotations are involved was analyzed for patients treated in the cranial region. Methods and Materials A total of 2185 initial (i.e. after pre-positioning the patient with the infrared system but before image guidance) patient setup errors (1705 in the cranial and 480 in the extracranial region) obtained by using ExacTrac (BrainLAB AG, Feldkirchen, Germany) were analyzed. Additionally, the patient setup errors as a function of the couch rotation angle were obtained by analyzing 242 setup errors in the cranial region. Before the couch was rotated, the patient setup error was corrected at couch rotation angle 0° with the aid of image guidance and the six degrees of freedom (6DoF) couch. For both situations attainment rates for two different tolerances (tolerance A: ±0.5 mm, ±0.5°; tolerance B: ±1.0 mm, ±1.0°) were calculated. Results The mean (± one standard deviation) initial patient setup errors for the cranial cases were -0.24 ± 1.21°, -0.23 ± 0.91° and -0.03 ± 1.07° for the pitch, roll and couch rotation axes and 0.10 ± 1.17 mm, 0.10 ± 1.62 mm and 0.11 ± 1.29 mm for the lateral, longitudinal and vertical axes, respectively. Attainment rate (all six axes simultaneously) for tolerance A was 0.6% and 13.1% for tolerance B, respectively. For the extracranial cases the corresponding values were -0.21 ± 0.95°, -0.05 ± 1.08° and -0.14 ± 1.02° for the pitch, roll and couch rotation axes and 0.15 ± 1.77 mm, 0.62 ± 1.94 mm and -0.40 ± 2.15 mm for the lateral, longitudinal and vertical axes. Attainment rate (all six axes simultaneously) for tolerance A was 0.0% and 3.1% for tolerance B, respectively. After initial setup correction and rotation of the couch to treatment position a re-correction has to be performed in 77.4% of all cases to fulfill tolerance A and in 15.6% of all cases to fulfill tolerance B. Conclusion The analysis of the data shows that all six axes of a 6DoF couch are used extensively for patient setup in clinical routine. In order to fulfill high patient setup accuracies (e.g. for stereotactic treatments), a 6DoF couch is recommended. Moreover, re-verification of the patient setup after rotating the couch is required in clinical routine.

Purpose Different international target volume delineation guidelines exist and different treatment techniques are available for salvage radiation therapy (RT) for recurrent prostate cancer, but less is known regarding their respective applicability in clinical practice. Methods and Materials A randomized phase III trial testing 64 Gy vs 70 Gy salvage RT was accompanied by an intense quality assurance program including a site-specific and study-specific questionnaire and a dummy run (DR). Target volume delineation was performed according to the European Organisation for the Research and Treatment of Cancer guidelines, and a DR-based treatment plan was established for 70 Gy. Major and minor protocol deviations were noted, interobserver agreement of delineated target contours was assessed, and dose-volume histogram (DVH) parameters of different treatment techniques were compared. Results Thirty European centers participated, 43% of which were using 3-dimensional conformal RT (3D-CRT), with the remaining centers using intensity modulated RT (IMRT) or volumetric modulated arc technique (VMAT). The first submitted version of the DR contained major deviations in 21 of 30 (70%) centers, mostly caused by inappropriately defined or lack of prostate bed (PB). All but 5 centers completed the DR successfully with their second submitted version. The interobserver agreement of the PB was moderate and was improved by the DR review, as indicated by an increased κ value (0.59 vs 0.55), mean sensitivity (0.64 vs 0.58), volume of total agreement (3.9 vs 3.3 cm 3 ), and decrease in the union volume (79.3 vs 84.2 cm 3 ). Rectal and bladder wall DVH parameters of IMRT and VMAT vs 3D-CRT plans were not significantly different. Conclusions The interobserver agreement of PB delineation was moderate but was improved by the DR. Major deviations could be identified for the majority of centers. The DR has improved the acquaintance of the participating centers with the trial protocol.

PURPOSE Radiation protection regulatory differentiates between primary and scatter radiation. Whereas for conventional clinical linear accelerators the solid angle for primary radiation is planar, the Cyberknife (Accuray Inc., Sunnyvale, CA) may point its beam in all spatial directions. In order to be able to judge on radiation protection calculations for a Cyberknife-M6 vault, the direction distribution for delivered plans was evaluated based on clinical experiences. METHODS The log-files of 121 delivered patient treatment plans were exported, divided into cranial and extra-cranial treatments and the delivered monitor units (MU) together with the corresponding beam directions were analyzed. This MU-weighted spatial distribution was then projected to a 9.5 × 5.9 × 3.9 m(3) vault, generating an "intensity map" using a binning of 50 × 50 cm(2) . The factor of direction (FOD) is reported as a fraction of the total applied MUs to the walls, ceiling and floor in the perspective of a patient lying in head-first-supine position on the couch. In this study, the term intFOD refers to the integral FOD and maxFOD refers to the maximal FOD for a single bin. RESULTS For all kind of treatments and collimators, intFOD and maxFOD for the wall behind the patient's head is 0.0. The intFOD for the floor varies between 0.65 and 0.74. For the ceiling, maxFOD is 0.002 and 0.0 for cranial and extra-cranial cases, respectively. The intFOD for the wall at the patient's feet, is 0.094 for cranial and 0.005 for extra-cranial cases. There is nearly no difference between the maxFOD of the right and left wall for cranial cases, whereas for extra-cranial cases these numbers differ by a factor of 1.75. CONCLUSION The varying FODs for the Cyberknife were quantified based on delivered treatment plans. These findings are helpful regarding the design of Cyberknife vaults.

Purpose: To create and test an accurate EPID-frame-based VMAT QA metric to detect gross dose errors in real-time and to provide information about the source of error. Methods: A Swiss cheese model was created for an EPID-based real-time QA process. The system compares a treatmentplan- based reference set of EPID images with images acquired over each 2° gantry angle interval. The metric utilizes a sequence of independent consecutively executed error detection Methods: a masking technique that verifies infield radiation delivery and ensures no out-of-field radiation; output normalization checks at two different stages; global image alignment to quantify rotation, scaling and translation; standard gamma evaluation (3%, 3 mm) and pixel intensity deviation checks including and excluding high dose gradient regions. Tolerances for each test were determined. For algorithm testing, twelve different types of errors were selected to modify the original plan. Corresponding predictions for each test case were generated, which included measurement-based noise. Each test case was run multiple times (with different noise per run) to assess the ability to detect introduced errors. Results: Averaged over five test runs, 99.1% of all plan variations that resulted in patient dose errors were detected within 2° and 100% within 4° (∼1% of patient dose delivery). Including cases that led to slightly modified but clinically equivalent plans, 91.5% were detected by the system within 2°. Based on the type of method that detected the error, determination of error sources was achieved. Conclusion: An EPID-based during-treatment error detection system for VMAT deliveries was successfully designed and tested. The system utilizes a sequence of methods to identify and prevent gross treatment delivery errors. The system was inspected for robustness with realistic noise variations, demonstrating that it has the potential to detect a large majority of errors in real-time and indicate the error source. J. V. Siebers receives funding support from Varian Medical Systems.

PURPOSE To estimate the dosimetric potential of mixed beam radiotherapy (MBRT) by using a single process optimizing the shape and weight of photon and electron apertures simultaneously based on Monte Carlo beamlet dose distributions. METHODS A simulated annealing based direct aperture optimization capable to perform simultaneous optimization was developed to generate treatment plans for MERT, photon-IMRT and MBRT. Both photon and electron apertures are collimated with the photon-MLC and are delivered in a segmented manner. For dosimetric comparison and for investigating the dependency on the number of apertures, photon-IMRT, MERT and MBRT plans were generated for an academic case consisting of a water phantom containing two shallow PTVs differing in the maximal depth of 5 and 7 cm, respectively and two OARs in distal and lateral direction to the PTVs. RESULTS For the superficial PTV, the dose homogeneity (V95%-V107%) and the mean dose (in percent of the prescribed dose) to the distal and the lateral OARs of the MBRT plan (94.9%, 16.9%, 17.8%) are superior or comparable to those for the MERT (74%, 18.4%, 15.4%) and the photon-IMRT plan (89.4%, 20.8%, 24.7%). For the enlarged PTV, the dosimetric superiority of MBRT compared to MERT and photon-IMRT is even more pronounced. Furthermore, an MBRT plan with 12 electron and 10 photon apertures lead to an objective function value 38% lower than that of a photon-IMRT plan with 40 apertures. CONCLUSION The results of simultaneous optimization for MBRT are promising with regards to further OAR sparing and improved dose coverage to the PTV compared to photon-IMRT and MERT. Especially superficial targets with deeper subparts (>5 cm) could substantially benefit. Moreover, MBRT seems to be a possible solution of two downsides of photon-IMRT, namely the extended low dose bath and the requirement of numerous apertures. This work was supported by Varian Medical Systems. This work was supported by Varian Medical Systems.

PURPOSE Performing pre-treatment quality assurance (QA) with the Delta4 system (ScandiDos Inc., Madison, WI) is well established for linac-based radiotherapy. This is not true when using a Cyberknife (Accuray Inc., Sunnyvale, CA) where, typically film-based QA is applied. The goal of this work was to test the feasibility to use the Delta4 system for pre-treatment QA for stereotactic body radiation therapy (SBRT) using a Cyberknife-M6 equipped with the InCise2 multileaf collimator (MLC). METHODS In order to perform measurements without accelerator pulse signal, the Tomotherapy option within the Delta4 software was used. Absolute calibration of the Delta4 phantom was performed using a 10×10 cm(2) field shaped by the InCise2 MLC of the Cyberknife-M6. Five fiducials were attached to the Delta4 phantom in order to be able to track the phantom before and during measurements. For eight SBRT treatment plans (two liver, two prostate, one lung, three bone metastases) additional verification plans were recalculated on the Delta4 phantom using MultiPlan. Dicom data was exported from MultiPlan and was adapted in order to be compatible with the Delta4 software. The measured and calculated dose distributions were compared using the gamma analysis of the Delta4 system. RESULTS All eight SBRT plans were successfully measured with the aid of the Delta4 system. In the mean, 98.0±1.9%, 95.8±4.1% and 88.40±11.4% of measured dose points passed the gamma analysis using a global dose deviation criterion of 3% (100% corresponds to the dose maximum) and a distance-to-agreement criterion of 3 mm, 2 mm and 1 mm, respectively, and a threshold of 20%. CONCLUSION Pre-treatment QA of SBRT plans using the Delta4 system on a Cyberknife-M6 is feasible. Measured dose distributions of SBRT plans showed clinically acceptable agreement with the corresponding calculated dose distributions.

PURPOSE To assess dose rates in volumetric modulated arc therapy (VMAT) plans. METHODS For dose rate analysis, using Monte Carlo methods, dose distributions are calculated in sectors of consecutive DICOM control points and each multiplied with the MU-rate obtaining dose rate distributions for every voxel at every time-point during a treatment fraction. Dose rate distributions were calculated for a clinical head and neck, cranial (2 Gy fraction dose) and a SBRT liver treatment case (5 Gy per fraction). To assess optimizer influence on dose rate distributions, five conventionally fractionated head and neck cases were optimized using the progressive resolution optimizer (PRO) versions 2 and 3 (Varian Medical Systems, Palo Alto, CA). RESULTS Firstly, histograms of dose rates over the course of treatment delivery in volumes of interest were generated for the PTV and spine or brainstem of the clinical treatment plans. Secondly, dose rates were assessed as color wash overlay on top of CT slices, allowing the user to explore the dose rate variation over time. For the cases considered, dose rates were spread out over a continuous spectrum with a mean value in the lower half. PRO3 generated plans showed higher maximum dose rates compared to PRO2 (699.80 cGy/min vs. 543.46 cGy/min) and modulation of MU rates in blocks as opposed to gradual modulation. CONCLUSION Calculation and visualization of dose rate distributions in VMAT have been performed. Dose rates in clinical relevant VMAT cases are spread out over a continuous spectrum with a mean in the lower part for both conventional and SBRT test cases. Different optimization algorithms may lead to substantially different dose rate distributions in the same cases. The development of the Swiss Monte Carlo Plan framework has been partially supported by Varian Medical Systems.

PURPOSE The values in a PET image which represent activity concentrations of a radioactive tracer are influenced by a large number of parameters including patient conditions as well as image acquisition and reconstruction. This work investigates noise characteristics in PET images for various image acquisition and image reconstruction parameters. METHODS Different phantoms with homogeneous activity distributions were scanned using several acquisition parameters and reconstructed with numerous sets of reconstruction parameters. Images from six PET scanners from different vendors were analyzed and compared with respect to quantitative noise characteristics. Local noise metrics, which give rise to a threshold value defining the metric of hypoxic fraction, as well as global noise measures in terms of noise power spectra (NPS) were computed. In addition to variability due to different reconstruction parameters, spatial variability of activity distribution and its noise metrics were investigated. Patient data from clinical trials were mapped onto phantom scans to explore the impact of the scanner's intrinsic noise variability on quantitative clinical analysis. RESULTS Local noise metrics showed substantial variability up to an order of magnitude for different reconstruction parameters. Investigations of corresponding NPS revealed reconstruction dependent structural noise characteristics. For the acquisition parameters, noise metrics were guided by Poisson statistics. Large spatial non-uniformity of the noise was observed in both axial and radial direction of a PET image. In addition, activity concentrations in PET images of homogeneous phantom scans showed intriguing spatial fluctuations for most scanners. The clinical metric of the hypoxic fraction was shown to be considerably influenced by the PET scanner's spatial noise characteristics. CONCLUSION We showed that a hypoxic fraction metric based on noise characteristics requires careful consideration of the various dependencies in order to justify its quantitative validity. This work may result in recommendations for harmonizing QA of PET imaging for multi-institutional clinical trials.

Background To determine the outcome and patterns of failure in oral cavity cancer (OCC) patients after postoperative intensity modulated radiotherapy (IMRT) with concomitant systemic therapy. Methods All patients with locally advanced (AJCC stage III/IV) or high-risk OCC (AJCC stage II) who underwent postoperative IMRT at our institution between December 2006 and July 2010 were retrospectively analyzed. The primary endpoint was locoregional recurrence-free survival (LRRFS). Secondary endpoints included distant metastasis-free survival (DMFS), overall survival (OS), acute and late toxicities. Results Overall 53 patients were analyzed. Twenty-three patients (43%) underwent concomitant chemotherapy with cisplatin, two patients with carboplatin (4%) and four patients were treated with the monoclonal antibody cetuximab (8%). At a median follow-up of 2.3 (range, 1.1–4.6) years the 3-year LRRFS, DMFS and OS estimates were 79%, 90%, and 73% respectively. Twelve patients experienced a locoregional recurrence. Eight patients, 5 of which had both a flap reconstruction and extracapsular extension (ECE), showed an unusual multifocal pattern of recurrence. Ten locoregional recurrences occurred marginally or outside of the high-risk target volumes. Acute toxicity grades of 2 (27%) and 3 (66%) and late toxicity grades of 2 (34%) and 3 (11%) were observed. Conclusion LRRFS after postoperative IMRT is satisfying and toxicity is acceptable. The majority of locoregional recurrences occurred marginally or outside of the high-risk target volumes. Improvement of high-risk target volume definition especially in patients with flap reconstruction and ECE might transfer into better locoregional control.

Purpose: For shallow tumors, modulated electron radiotherapy (MERT) promises a reduction of dose to distal organs at risk. At our institution a framework was developed in order to create treatment plans for MERT employing both forward and inverse optimization. In this work, an efficient quality assurance (QA) process is established. Methods: Treatment plans for three different tumor sites were created using an inverse optimization. These plans consist of 6–12 segments and energies between 6 and 18 MeV. An already established QA process for photon IMRT plans is now extended to additionally handle MERT plans. First, the dose distributions are calculated in a homogenous water phantom. For this task a dedicated Monte Carlo (MC) framework for MERT is used. Second, the segments are applied on a stand-alone amorphous silicon electronic portal imaging device (EPID) using a source-to-surface distance of 70 cm. This device was calibrated for electron beams in a previous work. An in-house developed analysis software, is then utilized for comparisons and evaluation of the measured and calculated dose distributions. Results: For all three plans the calculated dose distributions agree well with the measured ones. Using a 2D gamma comparison (2% of dose max/2 mm and 10% dose threshold) passingmore » rates >98% are achieved.The dose calculation for each plan on the water phantom, using voxels of 0.2×0.2×0.2 cm{sup 3}, takes at maximum 30 min on a single core Pentium 2.66 GHz system with 6 GB RAM, to reach a statistical uncertainty of 2% (1 std. dev.). Conclusion: An already established QA procedure for IMRT photon plans was applied for MERT. The dedicated MC framework and the use of EPID measurements allow an efficient QA procedure in a clinical environment. This work was supported by Varian Medical Systems.« less

Purpose: : To report acute and late toxicity in prostate cancer patients treated by high-dose intensity-modulated radiation therapy (IMRT) with daily image-guidance. Patients and Methods: : From 06/2004-03/2008, 102 men were treated with 80 Gy IMRT with daily image-guidance. The risk groups were as follows: low, intermediate, and high risk in 21%, 27%, and 52% of patients, respectively. Hormone therapy was given to 65% of patients. Toxicity was scored according to the CTC scale version 3.0. Results: : Median age was 69 years and median follow-up was 39 months (range, 16-61 months). Acute and late grade 2 gastrointestinal (GI) toxicity occurred in 2% and 5% of patients, respectively, while acute and late grade 3 GI toxicity was absent. Grade 2 and 3 pretreatment genitourinary (GU) morbidity (PGUM) were 15% and 2%, respectively. Acute grade 2 and 3 GU toxicity were 43% and 5% and late grade 2 and 3 GU toxicity were 21% and 1%, respectively. After multiple Cox regression analysis, PGUM was an independent predictor of decreased late ≥ grade 2 GU toxicity-free survival (hazard ratio = 9.4 (95% confidence interval: 4.1, 22.0), p < 0.001). At the end of follow-up, the incidence of late grade 2 and 3 GU toxicity decreased to 7% and 1%, respectively. Conclusion: : GI toxicity rates after IMRT with daily image-guidance were excellent. GU toxicity rates were acceptable and strongly related to PGUM