Publications by authors named "Dietmar Georg"

205 Publications

Early morbidity and dose-volume effects in definitive radiochemotherapy for locally advanced cervical cancer: a prospective cohort study covering modern treatment techniques.

Strahlenther Onkol 2021 Apr 30. Epub 2021 Apr 30.

Department of Radiation Oncology, Comprehensive Cancer Center, Medical University of Vienna/AKH Wien, Währinger Gürtel 18-20, 1090, Vienna, Austria.

Purpose: Predicting morbidity for patients with locally advanced cervix cancer after external beam radiotherapy (EBRT) based on dose-volume parameters remains an unresolved issue in definitive radiochemotherapy. The aim of this prospective study was to correlate patient characteristics and dose-volume parameters to various early morbidity endpoints for different EBRT techniques, including volumetric modulated arc therapy (VMAT) and adaptive radiotherapy (ART).

Methods And Materials: The study population consisted of 48 patients diagnosed with locally advanced cervix cancer, treated with definitive radiochemotherapy including image-guided adaptive brachytherapy (IGABT). Multiple questionnaires (CTCAE 4.03, QLQ-C30 and EORTC QLQ-CX24) were assessed prospectively for patients treated with different EBRT techniques, including online adaptive VMAT. Contouring and treatment planning was based on the EMBRACE protocols. Acute toxicity, classified as general, gastrointestinal (GI) or genitourinary (GU) and their corresponding dose-volume histograms (DVHs) were first correlated by applying least absolute shrinkage and selection operator (LASSO) and subsequently evaluated by multiple logistic binomial regression.

Results: The treated EBRT volumes varied for the different techniques with ~2500 cm for 3D conformal radiotherapy (3D-CRT), ~2000 cm for EMBRACE‑I VMAT, and ~1800 cm for EMBRACE-II VMAT and ART. In general, a worsening of symptoms during the first 5 treatment weeks and recovery afterwards was observed. Dose-volume parameters significantly correlating with stool urgency, rectal and urinary incontinence were as follows: bowel V < 250 cm, rectum V < 80% and bladder V < 80-90%.

Conclusion: This prospective study demonstrated the impact of EBRT treatment techniques in combination with chemotherapy on early morbidity. Dose-volume effects for dysuria, urinary incontinence, stool urgency, diarrhea, rectal bleeding, rectal incontinence and weight loss were found.
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http://dx.doi.org/10.1007/s00066-021-01781-6DOI Listing
April 2021

Effects of a combined therapy of bortezomib and ionizing radiation on chondrosarcoma three-dimensional spheroid cultures.

Oncol Lett 2021 Jun 30;21(6):428. Epub 2021 Mar 30.

Department of Radiation Oncology, Medical University of Vienna, A-1090 Vienna, Austria.

Chondrosarcomas represent a heterogeneous group of primary bone cancers that are characterized by hyaline cartilaginous neoplastic tissue and are predominantly resistant to radiation and chemotherapy. However, adjuvant radiotherapy is often recommended in inoperable cases or after incomplete resections. To improve the efficiency of treatment, the present study tested a combination therapy with ionizing radiation (IR) and the proteasome inhibitor bortezomib. Using a three-dimensional (3D) spheroid model, 0-20 Gy of IR was applied to chondrosarcoma cells and healthy human chondrocytes. Following combined treatment with IR and bortezomib, the cell cycle distribution, apoptotic induction, the survivin pathway, autophagy and DNA damage were evaluated. Both cell types exhibited a slight decrease in viability following increasing doses of IR; the chondrosarcoma cells demonstrated a significant dose-dependent increase in the expression levels of the DNA damage marker histone H2AX phosphorylation at serine 139 (γH2AX). The combination treatment with bortezomib significantly decreased the cell viability after 48 h compared with that in irradiated cells. High-dose IR induced a G/M phase arrest, which was accompanied by a decrease in the number of cells at the G and S phase. Co-treatment with bortezomib changed the distribution of the cell cycle phases. The mRNA expression levels of the proapoptotic genes Bcl-2-associated X protein (Bax) and Bak were significantly increased by bortezomib treatment and combination therapy with IR. In addition, the combination therapy resulted in a synergistic decrease of the expression levels of survivin and its corresponding downstream pathway molecules, including heat shock protein 90, X-linked inhibitor of apoptosis protein, smad 2 and smad 3. Comparative analyses of γH2AX at 1 and 24 h post-IR revealed efficient DNA repair in human chondrosarcoma cells. Therefore, additional bortezomib treatment may only temporarily improve the radiation sensitivity of chondrosarcoma cells. However, the inhibition of the survivin pathway by the combined treatment with IR and bortezomib, observed in the present study, revealed a novel aspect in the tumor biology of chondrosarcoma 3D spheroid cultures and may represent a potential target for therapy.
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http://dx.doi.org/10.3892/ol.2021.12689DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045153PMC
June 2021

First application of the GPU-based software framework TIGRE for proton CT image reconstruction.

Phys Med 2021 Apr 10;84:56-64. Epub 2021 Apr 10.

Institute of High Energy Physics, Austrian Academy of Sciences, Vienna, Austria.

In proton therapy, the knowledge of the proton stopping power, i.e. the energy deposition per unit length within human tissue, is essential for accurate treatment planning. One suitable method to directly measure the stopping power is proton computed tomography (pCT). Due to the proton interaction mechanisms in matter, pCT image reconstruction faces some challenges: the unique path of each proton has to be considered separately in the reconstruction process adding complexity to the reconstruction problem. This study shows that the GPU-based open-source software toolkit TIGRE, which was initially intended for X-ray CT reconstruction, can be applied to the pCT image reconstruction problem using a straight line approach for the proton path. This simplified approach allows for reconstructions within seconds. To validate the applicability of TIGRE to pCT, several Monte Carlo simulations modeling a pCT setup with two Catphan® modules as phantoms were performed. Ordered-Subset Simultaneous Algebraic Reconstruction Technique (OS-SART) and Adaptive-Steepest-Descent Projection Onto Convex Sets (ASD-POCS) were used for image reconstruction. Since the accuracy of the approach is limited by the straight line approximation of the proton path, requirements for further improvement of TIGRE for pCT are addressed.
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http://dx.doi.org/10.1016/j.ejmp.2021.03.006DOI Listing
April 2021

Comparing the efficacy of γ- and electron-irradiation of PBMCs to promote secretion of paracrine, regenerative factors.

Mol Ther Methods Clin Dev 2021 Jun 24;21:14-27. Epub 2021 Feb 24.

Department of Thoracic Surgery, Medical University of Vienna, 1090 Vienna, Austria.

Cell-free secretomes represent a promising new therapeutic avenue in regenerative medicine, and γ-irradiation of human peripheral blood mononuclear cells (PBMCs) has been shown to promote the release of paracrine factors with high regenerative potential. Recently, the use of alternative irradiation sources, such as artificially generated β- or electron-irradiation, is encouraged by authorities. Since the effect of the less hazardous electron-radiation on the production and functions of paracrine factors has not been tested so far, we compared the effects of γ- and electron-irradiation on PBMCs and determined the efficacy of both radiation sources for producing regenerative secretomes. Exposure to 60 Gy γ-rays from a radioactive nuclide and 60 Gy electron-irradiation provided by a linear accelerator comparably induced cell death and DNA damage. The transcriptional landscapes of PBMCs exposed to either radiation source shared a high degree of similarity. Secretion patterns of proteins, lipids, and extracellular vesicles displayed similar profiles after γ- and electron-irradiation. Lastly, we detected comparable biological activities in functional assays reflecting the regenerative potential of the secretomes. Taken together, we were able to demonstrate that electron-irradiation is an effective, alternative radiation source for producing therapeutic, cell-free secretomes. Our study paves the way for future clinical trials employing secretomes generated with electron-irradiation in tissue-regenerative medicine.
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http://dx.doi.org/10.1016/j.omtm.2021.02.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7960502PMC
June 2021

An MR-only acquisition and artificial intelligence based image-processing protocol for photon and proton therapy using a low field MR.

Z Med Phys 2021 Feb 15;31(1):78-88. Epub 2021 Jan 15.

Division of Medical Radiation Physics, Department of Radiation Oncology, Medical University of Vienna, Vienna, Austria.

Objective: Recent developments on synthetically generated CTs (sCT), hybrid MRI linacs and MR-only simulations underlined the clinical feasibility and acceptance of MR guided radiation therapy. However, considering clinical application of open and low field MR with a limited field of view can result in truncation of the patient's anatomy which further affects the MR to sCT conversion. In this study an acquisition protocol and subsequent MR image stitching is proposed to overcome the limited field of view restriction of open MR scanners, for MR-only photon and proton therapy.

Material And Methods: 12 prostate cancer patients scanned with an open 0.35T scanner were included. To obtain the full body contour an enhanced imaging protocol including two repeated scans after bilateral table movement was introduced. All required structures (patient contour, target and organ at risk) were delineated on a post-processed combined transversal image set (stitched MRI). The postprocessed MR was converted into a sCT by a pretrained neural network generator. Inversely planned photon and proton plans (VMAT and SFUD) were designed using the sCT and recalculated for rigidly and deformably registered CT images and compared based on D2%, D50%, V70Gy for organs at risk and based on D2%, D50%, D98% for the CTV and PTV. The stitched MRI and the untruncated MRI were compared to the CT, and the maximum surface distance was calculated. The sCT was evaluated with respect to delineation accuracy by comparing on stitched MRI and sCT using the DICE coefficient for femoral bones and the whole body.

Results: Maximum surface distance analysis revealed uncertainties in lateral direction of 1-3mm on average. DICE coefficient analysis confirms good performance of the sCT conversion, i.e. 92%, 93%, and 100% were obtained for femoral bone left and right and whole body. Dose comparison resulted in uncertainties below 1% between deformed CT and sCT and below 2% between rigidly registered CT and sCT in the CTV for photon and proton treatment plans.

Discussion: A newly developed acquisition protocol for open MR scanners and subsequent Sct generation revealed good acceptance for photon and proton therapy. Moreover, this protocol tackles the restriction of the limited FOVs and expands the capacities towards MR guided proton therapy with horizontal beam lines.
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http://dx.doi.org/10.1016/j.zemedi.2020.10.004DOI Listing
February 2021

Tribute to David Thwaites.

Radiother Oncol 2020 Dec;153:5-6

German Cancer Research Center (DKFZ), Heidelberg, Germany.

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http://dx.doi.org/10.1016/j.radonc.2020.11.005DOI Listing
December 2020

MR-guided proton therapy: Impact of magnetic fields on the detector response.

Med Phys 2020 Dec 16. Epub 2020 Dec 16.

Division of Medical Physics, Department of Radiation Oncology, Medical University of Vienna, 1090, Vienna, Austria.

Purpose: To investigate the response of detectors for proton dosimetry in the presence of magnetic fields.

Material And Methods: Four ionization chambers (ICs), two thimble-type and two plane-parallel-type, and a diamond detector were investigated. All detectors were irradiated with homogeneous single-energy-layer fields, using 252.7 MeV proton beams. A Farmer IC was additionally irradiated in the same geometrical configuration, but with a lower nominal energy of 97.4 MeV. The beams were subjected to magnetic field strengths of 0, 0.25, 0.5, 0.75, and 1 T produced by a research dipole magnet placed at the room's isocenter. Detectors were positioned at 2 cm water equivalent depth, with their stem perpendicular to both the magnetic field lines and the proton beam's central axis, in the direction of the Lorentz force. Normality and two sample statistical Student's t tests were performed to assess the influence of the magnetic field on the detectors' responses.

Results: For all detectors, a small but significant magnetic field-dependent change of their response was found. Observed differences compared to the no magnetic field case ranged from +0.5% to -0.7%. The magnetic field dependence was found to be nonlinear and highest between 0.25 and 0.5 T for 252.7 MeV proton beams. A different variation of the Farmer chamber response with magnetic field strength was observed for irradiations using lower energy (97.4 MeV) protons. The largest magnetic field effects were observed for plane-parallel ionization chambers.

Conclusion: Small magnetic field-dependent changes in the detector response were identified, which should be corrected for dosimetric applications.
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http://dx.doi.org/10.1002/mp.14660DOI Listing
December 2020

Computer-assisted beam modeling for particle therapy.

Med Phys 2021 Feb 25;48(2):841-851. Epub 2020 Dec 25.

Division of Medical Radiation Physics, Department of Radiation Oncology, Medical University of Vienna, Währinger Gürtel 18-20, Vienna, 1090, Austria.

Purpose: To develop a computer-driven and thus less user-dependent method, allowing for a simple and straightforward generation of a Monte Carlo (MC) beam model of a scanned proton and carbon ion beam delivery system.

Methods: In a first step, experimental measurements were performed for proton and carbon ion energies in the available energy ranges. Data included depth dose profiles measured in water and spot sizes in air at various isocenter distances. Using an automated regularization-based optimization process (AUTO-BEAM), GATE/Geant4 beam models of the respective beam lines were generated. These were obtained sequentially by using least square weighting functions with and without regularization, to iteratively tune the beam parameters energy, energy spread, beam sigma, divergence, and emittance until a user-defined agreement was reached. Based on the parameter tuning for a set of energies, a beam model was semi-automatically generated. The resulting beam models were validated for all centers comparing to independent measurements of laterally integrated depth dose curves and spot sizes in air. For one representative center, three-dimensional dose cubes were measured and compared to simulations. The method was applied on one research as well as four different clinical beam lines for proton and carbon ions of three different particle therapy centers using synchrotron or cyclotron accelerator systems: (a) MedAustron ion therapy center, (b) University Proton Therapy Dresden, and (c) Center Antoine Lacassagne Nice.

Results: Particle beam ranges in the MC beam models agreed on average within 0.2 mm compared to measurements for all energies and beam lines. Spot sizes in air (full-width at half maximum) at all positions differed by less than 0.4% from the measurements. Dose calculation with the beam model for the clinical beam line at MedAustron agreed better than 1.7% in absolute dose for a representative clinical case treated with protons. For protons, beam model generation, including geometry creation, data conversion, and validation, was possible within three working days. The number of iterations required for the optimization process to converge, was found to be similar for all beam line geometries and particle types.

Conclusion: The presented method was demonstrated to work independently of the beam optics behavior of the different beam lines, particle types, and geometries. Furthermore, it is suitable for non-expert users and requires only limited user interaction. Beam model validation for different beam lines based on different beam delivery systems, showed good agreement.
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http://dx.doi.org/10.1002/mp.14647DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7986420PMC
February 2021

Technical Note: Design and commissioning of a water phantom for proton dosimetry in magnetic fields.

Med Phys 2021 Jan 8;48(1):505-512. Epub 2020 Dec 8.

Division of Medical Radiation Physics, Department of Radiation Oncology, Medical University of Vienna, Währinger Gürtel 18-20, Wien, 1090, Austria.

Purpose: To design and commission a water phantom suitable for constrained environments and magnetic fields for magnetic resonance (MR)-guided proton therapy.

Methods: A phantom was designed, to enable precise, remote controlled detector positioning in water within the constrained environment of a magnet for MR-guided proton therapy. The phantom consists of a PMMA enclosure whose outer dimensions of were chosen to optimize space usage inside the 13.5-cm bore gap of the magnet. The moving mechanism is based on a low-height H-shaped non-ferromagnetic belt drive, driven by stepper motors located outside of the magnetic field. The control system and the associated electronics were designed in house, with similar features as available in commercial water phantoms. Reproducibility as well as accuracy of the phantom positioning were tested using a high-precision Leica AT 402 laser tracker. Laterally integrated depth dose curves and lateral beam profiles at three depths were acquired repeatedly for a 148.2 MeV proton beam in water.

Results: The phantom was successfully operated with and without applied magnetic fields. For complex movements, a positioning uncertainty within 0.16 mm was found with an absolute accuracy typically below 0.3 mm. Laterally integrated depth dose curves agreed within 0.1 mm with data taken using a commercial water phantom. The lateral beam offset determined from beam profile measurements agreed well with data from Monte Carlo simulations.

Conclusion: The phantom is optimally suited for detector positioning and dosimetric experiments within constrained environments in high magnetic fields.
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http://dx.doi.org/10.1002/mp.14605DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7898880PMC
January 2021

Investigation of the Bragg peak degradation caused by homogeneous and heterogeneous lung tissue substitutes: proton beam experiments and comparison to current clinical dose calculation.

Phys Med Biol 2020 Nov 10. Epub 2020 Nov 10.

Department of Radiation Oncology, Medical University of Vienna, Wien, AUSTRIA.

Submillimetre structures of lung tissue are not represented in CT images used for radiotherapeutic dose calculation. In order to study the effect experimentally, lung substitutes with properties similar to lung tissue were chosen, namely two types of commercial lung tissue equivalent plates (LTEP) (CIRS, USA), two types of cork, balsawood, floral foam and konjac sponge. Laterally integrated dose profiles were measured as a function of depth (IDD) for proton pencil beams (PB) with an initial nominal energy of 97.4 and 148.2 MeV, respectively. The obtained dose profiles were investigated for their shifting and degradation of the Bragg peak (BP) caused by the materials, expressed as water equivalent thickness (WET) and full width half maximum (FWHM). The setup was simulated in the treatment planning system (TPS) RayStation using the Monte Carlo dose calculation algorithm. While the WET between experiment and dose calculation agreed within 0.5 mm, except for floral foam, the FWHM was underestimated in the TPS by up to 2.3 mm. Normalisation to the same mass thickness of the lung substitutes allowed to classify LTEPs and balsawood as homogeneous and cork, floral foam and konjac sponge as heterogeneous materials. The material specific BP degradation was up to 3.4 times higher for the heterogeneous samples. The modulation power as a measure for the heterogeneity was compared to the spectrum of Hounsfield units (HU) of the materials. A clear correlation was not found, but with further improvements the HU spectrum may serve as an indicator for the material heterogeneity. Further, MC simulations of binary voxel models using GATE/Geant4 were performed to investigate the influence of grain size and mass density. For mass densities similar to lung tissue the BP degradation had a maximum at 3 and 7 mm grain size.
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http://dx.doi.org/10.1088/1361-6560/abc938DOI Listing
November 2020

Grand challenges for medical physics in radiation oncology.

Radiother Oncol 2020 12 8;153:7-14. Epub 2020 Oct 8.

Servei de Radiofisica i Radioprotecció, Hospital Sant Pau, Barcelona, Spain.

Medical physics has made considerable contributions to recent advances in radiation oncology. Medical physicists are key players in the clinical and scientific radiation oncology context due to their unique skill sets, flexibility, clinical involvement and intrinsic translational character. The continuing development and widespread adoption of "high-tech" radiotherapy has led to an increased need for medical physics involvement. More recently, our field is rapidly changing towards an era of "precision oncology". These changes have opened new challenges for the definition of the professional and scientific roles and responsibilities of medical physicists. In this paper, we have identified four grand challenges of medical physics in radiation oncology: (1) improving target volume definition, (2) adoption of artificial intelligence and automation, (3) development of predictive models of biological effects for precision medicine, and (4) need for leadership. New visions and suggestions to orientate medical physics to successfully face these new challenges are summarized. We foresee that the scientific and professional challenges of our times are pushing medical physicists to accelerate toward multidisciplinarity. Medical physicists are expected to innovatively drive interactions and collaborations with other specialists outside radiation oncology while the radiation physics core will remain central. Medical physicists will retain strong and pivotal roles in quality, safety and in managing ever more complex technologies. The new challenges will require medical physicists to continuously update skills and innovate education, adapt curricula to include new fields, reinforce multi-disciplinary attitude and spirit of innovation. These challenges require visionary and open leadership, which is able to merge established roles with the exciting new fields where medical physics should increasingly contribute.
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http://dx.doi.org/10.1016/j.radonc.2020.10.001DOI Listing
December 2020

Hypofractionated stereotactic photon radiotherapy of choroidal melanoma: 20-year experience.

Acta Oncol 2021 Feb 24;60(2):207-214. Epub 2020 Sep 24.

Department of Ophthalmology, Medical University of Vienna, Vienna, Austria.

Background: To evaluate the long-term results after hypofractionated stereotactic photon radiotherapy (SRT) in patients with choroidal melanoma treated between 1997 and 2016.

Material And Methods: A total of 335 patients (183 male and 152 female) with choroidal melanoma unsuitable for ruthenium-106 brachytherapy or local resection were treated with linear accelerator-based SRT at the Medical University of Vienna. All patients received five fractions with either 10, 12 or 14 Gy per fraction. A complete ophthalmic examination including visual acuity and measurement of the tumor base and height using standardized A- and B-scan ultrasonography was performed every 3 months in the first 2 years, every 6 months until 5 years and yearly thereafter. Early and late adverse side effects were assessed at every follow-up visit.

Results: The median overall follow-up was 78.6 months (39.1 to 113.7 months). Local tumor control was 95.4% after 10 and 12 years, respectively. Fifty-four patients developed metastatic disease, and 31 died during the follow-up. Mean visual acuity decreased from 0.55 Snellen at baseline to 0.05 Snellen at the last individual follow-up. Ischemic retinopathy (192/335cases) and optic neuropathy (174/335cases) were the most common radiogenic side effects, followed by radiogenic cataract ( = 127), neovascular glaucoma ( = 71) and corneal epithelium defects ( = 49). Enucleation was performed in 54 patients mostly due to neovascular glaucoma ( = 41) or tumor recurrence ( = 10) during the study period. The eye retention rate was 79.7% after 10 and 12 years.

Conclusion: Hypofractionated stereotactic photon radiotherapy showed a high rate of local tumor control for choroidal melanoma and an acceptable rate of radiogenic side effects.
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http://dx.doi.org/10.1080/0284186X.2020.1820572DOI Listing
February 2021

Phantom-based quality assurance for multicenter quantitative MRI in locally advanced cervical cancer.

Radiother Oncol 2020 12 12;153:114-121. Epub 2020 Sep 12.

Department of Radiation Oncology, the Netherlands Cancer Institute, Amsterdam, the Netherlands.

Background And Purpose: A wide variation of MRI systems is a challenge in multicenter imaging biomarker studies as it adds variation in quantitative MRI values. The aim of this study was to design and test a quality assurance (QA) framework based on phantom measurements, for the quantitative MRI protocols of a multicenter imaging biomarker trial of locally advanced cervical cancer.

Materials And Methods: Fifteen institutes participated (five 1.5 T and ten 3 T scanners). Each institute optimized protocols for T2, diffusion-weighted imaging, T1, and dynamic contrast-enhanced (DCE-)MRI according to system possibilities, institutional preferences and study-specific constraints. Calibration phantoms with known values were used for validation. Benchmark protocols, similar on all systems, were used to investigate whether differences resulted from variations in institutional protocols or from system variations. Bias, repeatability (%RC), and reproducibility (%RDC) were determined. Ratios were used for T2 and T1 values.

Results: The institutional protocols showed a range in bias of 0.88-0.98 for T2 (median %RC = 1%; %RDC = 12%), -0.007 to 0.029 × 10 mm/s for the apparent diffusion coefficient (median %RC = 3%; %RDC = 18%), and 0.39-1.29 for T1 (median %RC = 1%; %RDC = 33%). For DCE a nonlinear vendor-specific relation was observed between measured and true concentrations with magnitude data, whereas the relation was linear when phase data was used.

Conclusion: We designed a QA framework for quantitative MRI protocols and demonstrated for a multicenter trial for cervical cancer that measurement of consistent T2 and apparent diffusion coefficient values is feasible despite protocol differences. For DCE-MRI and T1 mapping with the variable flip angle method, this was more challenging.
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http://dx.doi.org/10.1016/j.radonc.2020.09.013DOI Listing
December 2020

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

Phys Med 2020 Sep 29;77:187-193. Epub 2020 Aug 29.

Department of Radiation Oncology, Medical University Vienna, Austria. Electronic address:

Purpose: In-vitro radiobiological studies are essential for modelling the relative biological effectiveness (RBE) in proton therapy. The purpose of this study was to experimentally determine the RBE values in proton beams along the beam path for human prostate carcinoma cells (Du-145). RBE-dose and RBE-LET (dose-averaged linear energy transfer) dependencies were investigated and three phenomenological RBE models, i.e. McNamara, Rørvik and Wilkens were benchmarked for this cell line.

Methods: Cells were placed at multiple positions along the beam path, employing an in-house developed solid phantom. The experimental setup reflected the clinical prostate treatment scenario in terms of field size, depth, and required proton energies (127.2-180.1 MeV) and the physical doses from 0.5 to 6 Gy were delivered. The reference irradiation was performed with 200 kV X-ray beams. Respective (α/β) values were determined using the linear quadratic model and LET was derived from the treatment planning system at the exact location of cells.

Results And Conclusion: Independent of the cell survival level, all experimental RBE values were consistently higher in the target than the generic clinical RBE value of 1.1; with the lowest RBE value of 1.28 obtained at the beginning of the SOBP. A systematic RBE decrease with increasing dose was observed for the investigated dose range. The RBE values from all three applied models were considerably smaller than the experimental values. A clear increase of experimental RBE values with LET parameter suggests that proton LET must be taken into consideration for this low (α/β) tissue.
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http://dx.doi.org/10.1016/j.ejmp.2020.08.012DOI Listing
September 2020

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

Phys Med 2020 Aug 18;76:182-193. Epub 2020 Jul 18.

Division of Medical Radiation Physics, Department of Radiation Oncology, Medical University of Vienna, Vienna, Austria.

Purpose: The aim of the presented study was to complement existing literature on benchmarking proton dose by comparing dose calculations with experimental measurements in heterogeneous phantom. Points of interest inside and outside the target were considered to quantify the magnitude of calculation uncertainties in current and previous proton therapy practice that might especially have an impact on the dose in organs at risk (OARs).

Methods: The RayStation treatment planning system (RaySearch Laboratories), offering two dose calculation algorithms for pencil beam scanning in proton therapy, i.e., Pencil Beam (PB) and Monte Carlo (MC), was utilized. Treatment plans for a target located behind the interface of the heterogeneous tissues were generated. Dose measurements within and behind the target were performed in a water phantom with embedded slabs of various tissue equivalent materials and 24 PinPoint ionization chambers (PTW). In total 12 test configurations encompassing two different target depths, oblique beam incidence of 30 degrees and range shifter, were considered.

Results: PB and MC calculated doses agreed equally well with the measurements for all test geometries within the target, including the range shifter (mean dose differences ± 3%). Outside the target, the maximum dose difference of 9% (19%) was observed for MC (PB) for the oblique beam incidence and inserted range shifter.

Conclusion: The accuracy of MC dose algorithm was superior compared to the PB algorithm, especially outside the target volumes. MC based dose calculation should therefore be preferred in treatment scenarios with heterogeneities, especially to reduce clinically relevant uncertainties for OARs.
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http://dx.doi.org/10.1016/j.ejmp.2020.07.010DOI Listing
August 2020

Optimization for customized trajectories in cone beam computed tomography.

Med Phys 2020 Oct 29;47(10):4786-4799. Epub 2020 Aug 29.

Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria.

Purpose: We developed a target-based cone beam computed tomography (CBCT) imaging framework for optimizing an unconstrained three dimensional (3D) source-detector trajectory by incorporating prior image information. Our main aim is to enable a CBCT system to provide topical information about the target using a limited angle noncircular scan orbit with a minimal number of projections. Such a customized trajectory should include enough information to sufficiently reconstruct a particular volume of interest (VOI) under kinematic constraints, which may result from the patient size or additional surgical or radiation therapy-related equipment.

Methods: A patient-specific model from a prior diagnostic computed tomography (CT) volume is used as a digital phantom for CBCT trajectory simulations. Selection of the best projection views is accomplished through maximizing an objective function fed by the imaging quality provided by different x-ray positions on the digital phantom data. The final optimized trajectory includes a limited angular range and a minimal number of projections which can be applied to a C-arm device capable of general source-detector positioning. The performance of the proposed framework is investigated in experiments involving an in-house-built box phantom including spherical targets as well as an Alderson-Rando head phantom. In order to quantify the image quality of the reconstructed image, we use the average full-width-half-maximum (FWHM ) for the spherical target and feature similarity index (FSIM), universal quality index (UQI), and contrast-to-noise ratio (CNR) for an anatomical target.

Results: Our experiments based on both the box and head phantom showed that optimized trajectories could achieve a comparable image quality in the VOI with respect to the standard C-arm circular CBCT while using approximately one quarter of projections. We achieved a relative deviation <7% for FWHM between the reconstructed images from the optimized trajectories and the standard C-arm CBCT for all spherical targets. Furthermore, for the anatomical target, the relative deviation of FSIM, UQI, and CNR between the reconstructed image related to the proposed trajectory and the standard C-arm circular CBCT was found to be 5.06%, 6.89%, and 8.64%, respectively. We also compared our proposed trajectories to circular trajectories with equivalent angular sampling as the optimized trajectories. Our results show that optimized trajectories can outperform simple partial circular trajectories in the VOI in term of image quality. Typically, an angular range between 116° and 152° was used for the optimized trajectories.

Conclusion: We demonstrated that applying limited angle noncircular trajectories with optimized orientations in 3D space can provide a suitable image quality for particular image targets and has a potential for limited angle and low-dose CBCT-based interventions under strong spatial constraints.
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http://dx.doi.org/10.1002/mp.14403DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693244PMC
October 2020

Comparison of CBCT conversion methods for dose calculation in the head and neck region.

Z Med Phys 2020 Nov 30;30(4):289-299. Epub 2020 Jun 30.

Division of Medical Radiation Physics, Department of Radiation Oncology, Medical University of Vienna, Vienna, Austria. Electronic address:

The purpose of this study was to compare different methods of CBCT conversion respect to dose calculation accuracy. Twelve head and neck cancer patients treated with VMAT using simultaneous integrated boost technique were selected for the study. For each patient a planning CT (pCT), a control. CT acquired in the fourth week of treatment and a CBCT scan acquired on the closest day with the control CT were used. In order to re-calculate dose directly on CBCT image sets, a population based approach (CBCT) and a Histogram Matching (HM) approach based on rigid (CBCT) and deformable registration (CBCT) were used. Additionally, virtual CTs (vCTs) were generated using two deformable image registration algorithms (CT and CT) of the planning CT to the CBCT by using two different deformable image registration (DIR) algorithms. The corresponding control CTs were selected as ground truth and dose distributions on CBCT were analyzed using 3D global gamma index analysis applying a threshold of 10% with respect to the prescribed dose. Using the 2%/2mm gamma criterion, the results were 89.9%(±8.3%), 94.1%(±5.0%), 94.3%(±5.7%), 96.1%(±3.9%), 93.4%(±6.3%) for the CBCT, CBCT, CBCT, CT and CT, respectively. On average, the HM and DIR techniques showed a higher accuracy compared to the population based approach, but Kruskal-Wallis test did not show significant difference among the investigated dose calculation techniques assuming p<0.05. More sophisticated CBCT dose calculation methods seem to improve the dose calculation accuracy, but statistical significance remains to be demonstrated.
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http://dx.doi.org/10.1016/j.zemedi.2020.05.007DOI Listing
November 2020

Latent space manipulation for high-resolution medical image synthesis via the StyleGAN.

Z Med Phys 2020 Nov 18;30(4):305-314. Epub 2020 Jun 18.

Department of Radiation Sciences, Umeå University, Umeå, Sweden.

Introduction: This paper explores the potential of the StyleGAN model as an high-resolution image generator for synthetic medical images. The possibility to generate sample patient images of different modalities can be helpful for training deep learning algorithms as e.g. a data augmentation technique.

Methods: The StyleGAN model was trained on Computed Tomography (CT) and T2- weighted Magnetic Resonance (MR) images from 100 patients with pelvic malignancies. The resulting model was investigated with regards to three features: Image Modality, Sex, and Longitudinal Slice Position. Further, the style transfer feature of the StyleGAN was used to move images between the modalities. The root-mean-squard error (RMSE) and the Mean Absolute Error (MAE) were used to quantify errors for MR and CT, respectively.

Results: We demonstrate how these features can be transformed by manipulating the latent style vectors, and attempt to quantify how the errors change as we move through the latent style space. The best results were achieved by using the style transfer feature of the StyleGAN (58.7 HU MAE for MR to CT and 0.339 RMSE for CT to MR). Slices below and above an initial central slice can be predicted with an error below 75 HU MAE and 0.3 RMSE within 4cm for CT and MR, respectively.

Discussion: The StyleGAN is a promising model to use for generating synthetic medical images for MR and CT modalities as well as for 3D volumes.
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http://dx.doi.org/10.1016/j.zemedi.2020.05.001DOI Listing
November 2020

Characterization of the PTW-34089 type 147 mm diameter large-area ionization chamber for use in light-ion beams.

Phys Med Biol 2020 09 4;65(17):17NT02. Epub 2020 Sep 4.

Division of Medical Radiation Physics, Department of Radiation Oncology, Medical University of Vienna, Austria.

A newly-designed large-area plane-parallel ionization chamber (of type PTW 34089), denoted BPC150, with a nominal active volume diameter of 147 mm is characterized in this study. Such chambers exhibit benefits compared to smaller chambers in the field of scanned light-ion beam dosimetry because they capture a larger fraction of the laterally-spread beam fragments and ease positioning with respect to small fields. The chamber was characterized in Co, 200 kV x-ray, proton and carbon ion beams. The chamber-specific beam-quality correction factor k was determined. To investigate the homogeneity of the chamber's response, a radial response map was acquired. An edge correction was applied when the proton beam only partly impinged on the chamber's active surface. The measured response map showed that the response in the chamber's center is 3% lower than the average response over the total active area. Furthermore, percentage depth dose (PDD) curves in carbon ions were acquired and compared to those obtained with smaller-diameter chambers (i.e. 81.6 mm and 39.6 mm) as well as with results from Monte Carlo simulations. The measured absorbed dose to water cross calibration coefficients resulted in a k of 0.981 ± 0.020. Regarding carbon ion PDD curves, relative differences between the BPC150 and smaller chambers were observed, especially for higher energies and in the fragmentation tail. These differences reached 10%-22% in the fragmentation tail (compared to the 81.6 mm diameter chamber). Differences increased when comparing to a chamber with 39.6 mm diameter. The provided results characterize the BPC150 thoroughly for usage in scanned light-ion beam dosimetry and demonstrate its advantage of capturing a larger fraction of the laterally-integrated dose in the fragmentation tail.
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http://dx.doi.org/10.1088/1361-6560/ab9852DOI Listing
September 2020

Implementation of a dose calculation algorithm based on Monte Carlo simulations for treatment planning towards MRI guided ion beam therapy.

Phys Med 2020 Jun 29;74:155-165. Epub 2020 May 29.

Department of Radiation Oncology, Medical University of Vienna/AKH, Vienna, Austria; Christian Doppler Laboratory for Medical Radiation Research for Radiation Oncology, Medical University of Vienna, Vienna, Austria.

Magnetic resonance guidance in particle therapy has the potential to improve the current performance of clinical workflows. However, the presence of magnetic fields challenges the current algorithms for treatment planning. To ensure proper dose calculations, compensation methods are required to guarantee that the maximum deposited energy of deflected beams lies in the target volume. In addition, proper modifications of the intrinsic dose calculation engines, accounting for magnetic fields, are needed. In this work, an algorithm for proton treatment planning in magnetic fields was implemented in a research treatment planning system (TPS), matRad. Setup-specific look up tables were generated using a validated MC model for a clinical proton beamline (62.4 - 215.7 MeV) interacting with a dipole magnet (B = 0-1 T). The algorithm was successfully benchmarked against MC simulations in water, showing gamma index (2%/2mm) global pass rates higher than 96% for different plan configurations. Additionally, absorbed depth doses were compared with experimental measurements in water. Differences within 2% and 3.5% in the Bragg peak and entrance regions, respectively, were found. Finally, treatment plans were generated and optimized for magnetic field strengths of 0 and 1 T to assess the performance of the proposed model. Equivalent treatment plans and dose volume histograms were achieved, independently of the magnetic field strength. Differences lower than 1.5% for plan quality indicators (D, D, D, V and V) in water, a TG119 phantom and an exemplary prostate patient case were obtained. More complex treatment planning studies are foreseen to establish the limits of applicability of the proposed model.
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http://dx.doi.org/10.1016/j.ejmp.2020.04.027DOI Listing
June 2020

MR-guided proton therapy: a review and a preview.

Radiat Oncol 2020 May 29;15(1):129. Epub 2020 May 29.

Department of Medical Physics, Faculty of Physics, Ludwig-Maximilians-Universität München, Garching, Germany.

Background: The targeting accuracy of proton therapy (PT) for moving soft-tissue tumours is expected to greatly improve by real-time magnetic resonance imaging (MRI) guidance. The integration of MRI and PT at the treatment isocenter would offer the opportunity of combining the unparalleled soft-tissue contrast and real-time imaging capabilities of MRI with the most conformal dose distribution and best dose steering capability provided by modern PT. However, hybrid systems for MR-integrated PT (MRiPT) have not been realized so far due to a number of hitherto open technological challenges. In recent years, various research groups have started addressing these challenges and exploring the technical feasibility and clinical potential of MRiPT. The aim of this contribution is to review the different aspects of MRiPT, to report on the status quo and to identify important future research topics.

Methods: Four aspects currently under study and their future directions are discussed: modelling and experimental investigations of electromagnetic interactions between the MRI and PT systems, integration of MRiPT workflows in clinical facilities, proton dose calculation algorithms in magnetic fields, and MRI-only based proton treatment planning approaches.

Conclusions: Although MRiPT is still in its infancy, significant progress on all four aspects has been made, showing promising results that justify further efforts for research and development to be undertaken. First non-clinical research solutions have recently been realized and are being thoroughly characterized. The prospect that first prototype MRiPT systems for clinical use will likely exist within the next 5 to 10 years seems realistic, but requires significant work to be performed by collaborative efforts of research groups and industrial partners.
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http://dx.doi.org/10.1186/s13014-020-01571-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7260752PMC
May 2020

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

Med Phys 2020 Aug 15;47(8):3691-3702. Epub 2020 May 15.

Department of Radiation Oncology/Christian Doppler Laboratory for Medical Radiation Research for Radiation Oncology, Medical University of Vienna, Vienna, Austria.

Purpose: A relative biological effectiveness (RBE) of 1.1 is commonly used in clinical proton therapy, irrespective of tissue type and depth. This in vitro study was conducted to quantify the RBE of scanned protons as a function of the dose-averaged linear energy transfer (LET ) and the sensitivity factor (α/ß) . Additionally, three phenomenological models (McNamara, Rørvik, and Jones) and one mechanistic model (repair-misrepair-fixation, RMF) were applied to the experimentally derived data.

Methods: Four human cell lines (FaDu, HaCat, Du145, SKMel) with differential (α/ß) ratios were irradiated in a custom-designed irradiation setup with doses between 0 and 6 Gy at proximal, central, and distal positions of a 80 mm spread-out Bragg peak (SOBP) centered at 80 mm (setup A: proton energies 66.5-135.6 MeV) and 155 mm (setup B: proton energies 127.2-185.9 MeV) depth, respectively. LET values at the respective cell positions were derived from Monte Carlo simulations performed with the treatment planning system (TPS, RayStation). Dosimetric measurements were conducted to verify dose homogeneity and dose delivery accuracy. RBE values were derived for doses that resulted in 90 % (RBE ) and 10 % (RBE ) of cell survival, and survival after a 0.5 Gy dose (RBE ), 2 Gy dose (RBE ), and 6 Gy dose (RBE ).

Results: LET values at sample positions were 1.9, 2.1, 2.5, 2.8, 4.1, and 4.5 keV/µm. For the cell lines with high (α/ß) ratios (FaDu, HaCat), the LET did not impact on the RBE. For low (α/ß) cell lines (Du145, SKMel), LQ-derived survival curves indicated a clear correlation of LET and RBE. RBE values up to 2.9 and RBE values between 1.4 and 1.8 were obtained. Model-derived RBE predictions slightly overestimated the RBE for the high (α/ß) cell lines, although all models except the Jones model provided RBE values within the experimental uncertainty. For low (α/ß) cell lines, no agreement was found between experiments and model predictions, that is, all models underestimated the measured RBE.

Conclusions: The sensitivity parameter (α/ß) was observed to be a major influencing factor for the RBE of protons and its sensitivity toward LET changes. RBE prediction models are applicable for high (α/ß) cell lines but do not estimate RBE values with sufficient accuracy in low (α/ß) cell lines.
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http://dx.doi.org/10.1002/mp.14212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7496287PMC
August 2020

Investigating conditional GAN performance with different generator architectures, an ensemble model, and different MR scanners for MR-sCT conversion.

Phys Med Biol 2020 05 22;65(10):105004. Epub 2020 May 22.

Division of Medical Radiation Physics, Department of Radiation Oncology, Medical University of Vienna, Vienna, Austria. Medical Imaging Cluster, Medical University of Vienna, Vienna , Austria.

Recent developments in magnetic resonance (MR) to synthetic computed tomography (sCT) conversion have shown that treatment planning is possible without an initial planning CT. Promising conversion results have been demonstrated recently using conditional generative adversarial networks (cGANs). However, the performance is generally only tested on images from one MR scanner, which neglects the potential of neural networks to find general high-level abstract features. In this study, we explored the generalizability of the generator models, trained on a single field strength scanner, to data acquired with higher field strengths. T2-weighted 0.35T MRIs and CTs from 51 patients treated for prostate (40) and cervical cancer (11) were included. 25 of them were used to train four different generators (SE-ResNet, DenseNet, U-Net, and Embedded Net). Further, an ensemble model was created from the four network outputs. The models were validated on 16 patients from a 0.35T MR scanner. Further, the trained models were tested on the Gold Atlas dataset, containing T2-weighted MR scans of different field strengths; 1.5T(7) and 3T(12), and 10 patients from the 0.35T scanner. The sCTs were dosimetrically compared using clinical VMAT plans for all test patients. For the same scanner (0.35T), the results from the different models were comparable on the test set, with only minor differences in the mean absolute error (MAE) (35-51HU body). Similar results were obtained for conversions of 3T GE Signa and the 3T GE Discovery images (40-62HU MAE) for three of the models. However, larger differences were observed for the 1.5T images (48-65HU MAE). The overall best model was found to be the ensemble model. All dose differences were below 1%. This study shows that it is possible to generalize models trained on images of one scanner to other scanners and different field strengths. The best metric results were achieved by the combination of all networks.
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http://dx.doi.org/10.1088/1361-6560/ab857bDOI Listing
May 2020

Particle therapy in Europe.

Mol Oncol 2020 07 22;14(7):1492-1499. Epub 2020 Apr 22.

Paul Scherrer Institute, Villigen, Switzerland.

Particle therapy using protons or heavier ions is currently the most advanced form of radiotherapy and offers new opportunities for improving cancer care and research. Ions deposit the dose with a sharp maximum - the Bragg peak - and normal tissue receives a much lower dose than what is delivered by X-ray therapy. Particle therapy has also biological advantages due to the high linear energy transfer of the charged particles around the Bragg peak. The introduction of particle therapy has been slow in Europe, but within the last decade, more than 20 clinical facilities have opened and facilitated access to this frontline therapy. In this review article, the basic concepts of particle therapy are reviewed along with a presentation of the current clinical indications, the European clinical research, and the established networks.
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http://dx.doi.org/10.1002/1878-0261.12677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332216PMC
July 2020

Dose- rather than fluence-averaged LET should be used as a single-parameter descriptor of proton beam quality for radiochromic film dosimetry.

Med Phys 2020 Jun 13;47(5):2289-2299. Epub 2020 Mar 13.

MedAustron Ion Therapy Centre/EBG MedAustron, Marie-Curie-Straße 5, 2700, Wiener Neustadt, Austria.

Purpose: The dose response of Gafchromic EBT3 films exposed to proton beams depends on the dose, and additionally on the beam quality, which is often quantified with the linear energy transfer (LET) and, hence, also referred to as LET quenching. Fundamentally different methods to determine correction factors for this LET quenching effect have been reported in literature and a new method using the local proton fluence distribution differential in LET is presented. This method was exploited to investigate whether a more practical correction based on the dose- or fluence-averaged LET is feasible in a variety of clinically possible beam arrangements.

Methods: The relative effectiveness (RE) was characterized within a high LET spread-out Bragg peak (SOBP) in water made up by the six lowest available energies (62.4-67.5 MeV, configuration " ") resulting in one of the highest clinically feasible dose-averaged LET distributions. Additionally, two beams were measured where a low LET proton beam (252.7 MeV) was superimposed on " ", which contributed either 50% of the initial particle fluence or 50% of the dose in the SOBP, referred to as configuration " " and " ," respectively. The proton LET spectrum was simulated with GATE/Geant4 at all measurement positions. The net optical density change differential in LET was integrated over the local proton spectrum to calculate the net optical density and therefrom the beam quality correction factor. The LET dependence of the film response was accounted for by an LET dependence of one of the three parameters in the calibration function and was determined from inverse optimization using measurement " ." This method was then validated on the measurements of " " and " " and subsequently used to calculate the RE at 900 positions in nine clinically relevant beams. The extrapolated RE set was used to derive a simple linear correction function based on dose-averaged LET ( ) and verify the validity in all points of the comprehensive RE set.

Results: The uncorrected film dose deviated up to 26% from the reference dose, whereas the corrected film dose agreed within 3% in all three beams in water (" ", " " and " "). The LET dependence of the calibration function started to strongly increase around 5 keV/μm and flatten out around 30 keV/μm. All REs calculated from the proton fluence in the nine simulated beams could be approximated with a linear function of dose-averaged LET (RE = 1.0258-0.0211 μm/keV ). However, no functional relationship of RE- and fluence-averaged LET could be found encompassing all beam energies and modulations.

Conclusions: The film quenching was found to be nonlinear as a function of proton LET as well as of the dose-averaged LET. However, the linear relation of RE on dose-averaged LET was a good approximation in all cases. In contrast to dose-averaged LET, fluence-averaged LET could not describe the RE when multiple beams were applied.
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http://dx.doi.org/10.1002/mp.14097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7318138PMC
June 2020

An analytical formalism for the assessment of dose uncertainties due to positioning uncertainties.

Med Phys 2020 Mar 26;47(3):1357-1363. Epub 2020 Jan 26.

EBG MedAustron GmbH, Marie-Curie Straße 5, 2700, Wiener Neustadt, Austria.

Purpose: To present an analytical formalism for the in depth assessment of uncertainties of field output factors in small fields related to detector positioning based on dose profile measurements. Additionally, a procedure for the propagation of these uncertainties was developed.

Methods: Based on the assumption that one dimensional and two dimensional second-order polynomial functions can be fitted to dose profiles of small photon beams, equations for the calculation of the expectation value, the variance, and the standard deviation were developed. The following fitting procedures of the dose profiles were considered: A one-dimensional case (1D), a quasi two-dimensional case (2Dq) based on independently measured line profiles and a full 2D case (2Df) which also considers cross-correlations in a two-dimensional dose distribution. A rectangular and a Gaussian probability density function (PDF) characterizing the probability of possible positions of the detector relative to the maximum dose were used. Uncertainty components such as the finite resolution of the scanning water phantom, the reproducibility of the determination of the position of the maximum dose, and the reproducibility of the collimator system were investigated. This formalism was tested in a 0.5 x 0.5 cm photon field where dose profiles were measured using a radiochromic film, a synthetic diamond detector, and an unshielded diode detector. Additionally, the dose distribution measured with the radiochromic film was convoluted with a convolution kernel mimicking the active volume of the unshielded diode.

Results: Analytic expressions for the calculation of uncertainties on field output factors were found for the 1D, the 2Dq, and the 2Df case. The uncertainty of the field output factor related to the relative position of the detector to the maximum dose increased quadratically with increasing limits of possible detector positions. Analysis of the radiochromic film showed that the 2Dq case gave a more conservative assessment of the uncertainty compared to the 2Df case with a difference of < 0.1%. The 2Dq case applied to the film measurements agreed well with the same approach as was applied to the unshielded diode. The investigated uncertainty components propagated to an uncertainty of the field output factors of 0.5% and 0.4% for the synthetic diamond and the unshielded diode, respectively. Additionally, the expectation value was lower than the maximum dose. The difference was 0.4% and 0.3% for the synthetic diamond and the unshielded diode, respectively.

Conclusions: The assessment of uncertainties of field output factors related to detector positioning is feasible using the proposed formalism. The 2Dq case is applicable when using online detectors. Accurate positioning in small fields is essential for accurate dosimetry as its related uncertainty increases quadratically. The observed drop of the expectation value needs to be considered in small field dosimetry.
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http://dx.doi.org/10.1002/mp.13991DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078844PMC
March 2020

4D perfusion CT of prostate cancer for image-guided radiotherapy planning: A proof of concept study.

PLoS One 2019 19;14(12):e0225673. Epub 2019 Dec 19.

Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria.

Purpose: Advanced forms of prostate cancer (PCa) radiotherapy with either external beam therapy or brachytherapy delivery techniques aim for a focal boost and thus require accurate lesion localization and lesion segmentation for subsequent treatment planning. This study prospectively evaluated dynamic contrast-enhanced computed tomography (DCE-CT) for the detection of prostate cancer lesions in the peripheral zone (PZ) using qualitative and quantitative image analysis compared to multiparametric magnet resonance imaging (mpMRI) of the prostate.

Methods: With local ethics committee approval, 14 patients (mean age, 67 years; range, 57-78 years; PSA, mean 8.1 ng/ml; range, 3.5-26.0) underwent DCE-CT, as well as mpMRI of the prostate, including standard T2, diffusion-weighted imaging (DWI), and DCE-MRI sequences followed by transrectal in-bore MRI-guided prostate biopsy. Maximum intensity projections (MIP) and DCE-CT perfusion parameters (CTP) were compared between healthy and malignant tissue. Two radiologists independently rated image quality and the tumor lesion delineation quality of PCa using a five-point ordinal scale. MIP and CTP were compared using visual grading characteristics (VGC) and receiver operating characteristics (ROC)/area under the curve (AUC) analysis.

Results: The PCa detection rate ranged between 57 to 79% for the two readers for DCE-CT and was 92% for DCE-MRI. DCE-CT perfusion parameters in PCa tissue in the PZ were significantly different compared to regular prostate tissue and benign lesions. Image quality and lesion visibility were comparable between DCE-CT and DCE-MRI (VGC: AUC 0.612 and 0.651, p>0.05).

Conclusion: Our preliminary results suggest that it is feasible to use DCE-CT for identification and visualization, and subsequent segmentation for focal radiotherapy approaches to PCa.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0225673PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6922381PMC
April 2020

The influence of errors in small field dosimetry on the dosimetric accuracy of treatment plans.

Acta Oncol 2020 May 7;59(5):511-517. Epub 2019 Nov 7.

Department of Radiation Oncology, Division Medical Physics, Medical University Vienna, Vienna, Austria.

Dosimetric effects of inaccuracies of output factors (OFs) implemented in treatment planning systems (TPSs) were investigated. Modified beam models (MBM) for which the OFs of small fields (down to 1 × 1 cm) were increased by up to 12% compared to the original beam models (OBM) were created for two TPSs. These beam models were used to recalculate treatment plans of different complexity. Treatment plans using stereotactic 3D-conformal (s3D-CRT) for brain metastasis as well as VMAT plans for head and neck and prostate cancer patients were generated. Dose distributions calculated with the MBM and the OBM were compared to measured dose distributions acquired using film dosimetry and a 2D-detector-array. For the s3D-CRT plans the calculated and measured dose at the isocenter was evaluated. For VMAT, gamma pass rates (GPRs) were calculated using global gamma index with 3%/3 mm, 2%/3 mm, 1%/3 mm and 2%/2 mm with a 20% threshold. Contribution of small fields to the total fluence was expressed as the ratio (F) of fluence trough leaf openings smaller than 2 cm to the total fluence. Using film dosimetry for the s3D-CRT plans, the average of the ratio of calculated dose to measured dose at the isocenter was 1.01 and 1.06 for the OBM and MBM model, respectively. A significantly lower GPR of the MBM compared to the OBM was only found for the localized prostate cases ( = 12.4%) measured with the 2D-detector-array and an acceptance criterion of 1%/3 mm. The effects of uncertainties in small field OFs implemented in TPSs are most pronounced for s3D-CRT cases and can be clearly identified using patient specific quality assurance. For VMAT these effects mainly remain undetected using standard patient specific quality assurance. Using tighter acceptance criteria combined with an analysis of the fluence generated by small fields can help identifying inaccuracies of OFs implemented in TPSs.
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http://dx.doi.org/10.1080/0284186X.2019.1685127DOI Listing
May 2020