Publications by authors named "Dietmar Georg"

221 Publications

First application of the BIANCA biophysical model to carbon-ion patient cases.

Phys Med Biol 2022 May 16. Epub 2022 May 16.

Physics Department, University of Pavia, via Bassi 6, Pavia, 27100, ITALY.

Objective: This manuscript presents the first application, of the BIANCA (BIophysical ANalysis of Cell death and chromosome Aberrations) biophysical model to the Relative Biological Effectiveness (RBE) calculation for carbon-ion cancer patients, and comparison of the outcomes with the clinical LEM I model. The continuous development of heavy-ion cancer therapy requires modelling of biological effects of ion beams on tumours and normal tissues. The RBE of heavy ions is higher than that of protons, with a significant variation along the beam path. Therefore, it requires precise modelling, especially for the pencil-beam scanning technique. Currently, two radiobiological models, LEM I and MKM, are in use for heavy ions in scanned pencil-beam facilities.

Approach: Utilizing an interface with the FLUKA Particle Therapy Tool, BIANCA was applied to re-calculate the RBE-weighted dose distribution for carbon-ion treatment of three patients (chordoma, head-and-neck and prostate) previously irradiated at CNAO, where radiobiological optimization was based on LEM I. The predictions obtained by BIANCA were based either on chordoma cell survival (RBE), or on dicentric aberrations in peripheral blood lymphocytes (RBE), which are indicators of late normal tissue damage, including secondary tumours. The simulation outcomes were then compared with those provided by LEM I.

Main Results: While in the target and in the entrance channel BIANCA predictions were lower than those obtained by LEM I, the two models provided very similar results in the considered OAR. The observed differences between$RBEand RBE_suggest that in normal tissues the information on cell survival should be integrated by information more closely related to the induction of late damage, such as chromosome aberrations.

Significance: This work showed that BIANCA is suitable for treatment plan optimization in ion-beam therapy, especially considering that it can predict both cell survival and chromosome aberrations and has previously shown good agreement with carbon-ion experimental data.
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http://dx.doi.org/10.1088/1361-6560/ac702bDOI Listing
May 2022

Impact of beamline-specific particle energy spectra on clinical plans in carbon ion beam therapy.

Med Phys 2022 Apr 13. Epub 2022 Apr 13.

MedAustron Ion Therapy Centre, Wiener Neustadt, Austria.

Purpose: The Local Effect Model version one (LEM I) is applied clinically across Europe to quantify the relative biological effectiveness (RBE) of carbon ion beams. It requires the full particle fluence spectrum differential in energy in each voxel as input parameter. Treatment planning systems (TPSs) use beamline-specific look-up tables generated with Monte Carlo (MC) codes. In this study, the changes in RBE weighted dose were quantified using different levels of details in the simulation or different MC codes.

Methods: The particle fluence differential in energy was simulated with FLUKA and Geant4 at 500 depths in water in 1-mm steps for 58 initial carbon ion energies (between 120.0 and 402.8 MeV/u). A dedicated beam model was applied, including the full description of the Nozzle using GATE-RTionV1.0 (Geant4.10.03p03). In addition, two tables generated with FLUKA were compared. The starting points of the FLUKA simulations were phase space (PhS) files from, firstly, the Geant4 nozzle simulations, and secondly, a clinical beam model where an analytic approach was used to mimic the beamline. Treatment plans (TPs) were generated with RayStation 8B (RaySearch Laboratories AB, Sweden) for cubic targets in water and 10 clinical patient cases using the clinical beam model. Subsequently, the RBE weighted dose was re-computed using the two other fluence tables (FLUKA PhS or Geant4).

Results: The fluence spectra of the primary and secondary particles simulated with Geant4 and FLUKA generally agreed well for the primary particles. Differences were mainly observed for the secondary particles. Interchanging the two energy spectra (FLUKA vs. GEANT4) to calculate the RBE weighted dose distributions resulted in average deviations of less than 1% in the entrance up to the end of the target region, with a maximum local deviation at the distal edge of the target. In the fragment tail, larger discrepancies of up to 5% on average were found for deep-seated targets. The patient and water phantom cases demonstrated similar results.

Conclusion: RBE weighted doses agreed well within all tested setups, confirming the clinical beam model provided by the TPS vendor. Furthermore, the results showed that the open source and generally available MC code Geant4 (in particular using GATE or GATE-RTion) can also be used to generate basic beam data required for RBE calculation in carbon ion therapy.
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http://dx.doi.org/10.1002/mp.15652DOI Listing
April 2022

Ganetespib selectively sensitizes cancer cells for proximal and distal spread-out Bragg peak proton irradiation.

Radiat Oncol 2022 Apr 11;17(1):72. Epub 2022 Apr 11.

Laboratory for Applied Radiobiology, Department of Radiation Oncology, University Hospital Zurich, University of Zurich, Winterthurerstr. 190, 8057, Zurich, Switzerland.

Objective: Hypersensitivity towards proton versus photon irradiation was demonstrated in homologous recombination repair (HRR)-deficient cell lines. Hence, combined treatment concepts targeting HRR provide a rational for potential pharmaceutical exploitation. The HSP90 inhibitor ganetespib (STA-9090) downregulates a multitude of HRR-associated proteins and sensitizes for certain chemotherapeutics. Thus, the radiosensitizing effect of HSP90-inhibiting ganetespib was investigated for reference photon irradiation and proton irradiation at a proximal and distal position in a spread-out Bragg peak (SOBP).

Methods: A549 and FaDu cells were treated with low-dose (2 nM resp. 1 nM) ganetespib and irradiated with 200 kV photons. Proton irradiation was performed at a proximal and a distal position within a SOBP, with corresponding dose-averaged linear-energy transfer (LET) values of 2.1 and 4.5 keV/µm, respectively. Cellular survival data was fitted to the linear-quadratic model to calculate relative biological effectiveness (RBE) and the dose-modifying factor (DMF). Additionally, A549 cells were treated with increasing doses of ganetespib and investigated by flow cytometry, immunoblotting, and immunofluorescence microscopy to investigate cell cycle distribution, Rad51 protein levels, and γH2AX foci, respectively.

Results: Low-dosed ganetespib significantly sensitized both cancer cell lines exclusively for proton irradiation at both investigated LET, resulting in increased RBE values of 10-40%. In comparison to photon irradiation, the fraction of cells in S/G2/M phase was elevated in response to proton irradiation with 10 nM ganetespib consistently reducing this population. No changes in cell cycle distribution were detected in unirradiated cells by ganetespib alone. Protein levels of Rad51 are downregulated in irradiated A549 cells by 10 nM and also 2 nM ganetespib within 24 h. Immunofluorescence staining demonstrated similar induction and removal of γH2AX foci, irrespective of irradiation type or ganetespib administration.

Conclusion: Our findings illustrate a proton-specific sensitizing effect of low-dosed ganetespib in both employed cell lines and at both investigated SOBP positions. We provide additional experimental data on cellular response and a rational for future combinatorial approaches with proton radiotherapy.
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http://dx.doi.org/10.1186/s13014-022-02036-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8996402PMC
April 2022

The Influence of Motion on the Delivery Accuracy When Comparing Actively Scanned Carbon Ions versus Protons at a Synchrotron-Based Radiotherapy Facility.

Cancers (Basel) 2022 Mar 31;14(7). Epub 2022 Mar 31.

MedAustron Ion Therapy Centre, Medical Physics, 2700 Wiener Neustadt, Austria.

Motion amplitudes, in need of mitigation for moving targets irradiated with pulsed carbon ions and protons, were identified to guide the decision on treatment and motion mitigation strategy. Measurements with PinPoint ionisation chambers positioned in an anthropomorphic breathing phantom were acquired to investigate different tumour motion scenarios, including rib and lung movements. The effect of beam delivery dynamics and spot characteristics was considered. The dose in the tumour centre was deteriorated up to 10% for carbon ions but only up to 5% for protons. Dose deviations in the penumbra increased by a factor of two when comparing carbon ions to protons, ranging from 2 to 30% for an increasing motion amplitude that was strongly dependent on the beam intensity. Layer rescanning was able to diminish the dose distortion caused by tumour motion, but an increase in spot size could reduce it even further to 5% within the target and 10% at the penumbra. An increased need for motion mitigation of carbon ions compared to protons was identified to assure target coverage and sparing of adjacent organs at risk in the penumbra region and outside the target. For the clinical implementation of moving target treatments at a synchrotron-based particle facility complex, time dependencies needed to be considered.
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http://dx.doi.org/10.3390/cancers14071788DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8997550PMC
March 2022

Roadmap: helium ion therapy.

Phys Med Biol 2022 Apr 8. Epub 2022 Apr 8.

GSI, Planckstraße 1, 64291 Darmstadt, Darmstadt, Hessen, 64291, GERMANY.

Helium ion beam therapy for the treatment of cancer was one of several developed and studied particle modalities in the 1950's, leading to clinical trials beginning in 1975 at the Lawrence Berkeley National Laboratory. The trial shutdown was followed by decades of research and clinical silence on the topic while proton and carbon ion therapy made debuts at research facilities and academic hospitals worldwide. The lack of progression in understanding of principle facets of helium ion beam therapy in terms of physics, biological and clinical findings persist today, mainly attributable to its highly limited availability. Despite this major setback, there has been an increasing focus on evaluating and establishing clinical and research programs using helium ion beams, with both therapy and imaging initiatives to supplement the clinical palette of radiotherapy in the treatment of aggressive disease and sensitive clinical cases. Moreover, due its intermediate physical and radio-biological properties between proton and carbon ion beams, helium ions may provide a streamlined economic steppingstone towards an era of widespread use of multi-particle approaches to light and heavy ion therapy. This roadmap presents an overview of the current state-of-the-art and future directions of helium ion therapy: understanding physics and improving modeling, understanding biology and improving modeling, imaging techniques using helium ions and refining and establishing clinical approaches and aims from learned experience with protons. These topics are organized and presented into three main sections, outlining current and future tasks in establishing clinical and research programs using helium ion beams - A. Physics B. Biological and C. Clinical Perspectives.
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http://dx.doi.org/10.1088/1361-6560/ac65d3DOI Listing
April 2022

An external perpendicular magnetic field does not influence survival and DNA damage after proton and carbon ion irradiation in human cancer cells.

Z Med Phys 2022 Jan 17. Epub 2022 Jan 17.

Department of Radiation Oncology, Medical University of Vienna, Vienna, Austria; MedAustron Ion Therapy Center, Wiener Neustadt, Austria. Electronic address:

Background And Purpose: Magnetic field effects on the radiobiological effectiveness during treatment of magnetic resonance (MRI) guided particle therapy are being debated. This study aims at assessing the influence of a perpendicular magnetic field on the biological effects in two human cancer cell lines irradiated with proton or carbon ions.

Methods And Materials: In vitro cell irradiations were performed in water inside a perpendicular magnetic field of 0 and 1T for both protons and carbon ions. Samples were located in the center of a spread-out Bragg peak at 8cm water equivalent depth with a dose averaged linear energy transfer (LET) of 4.2 or 83.4keV/μm for protons and carbon ions, respectively. Physical dose levels of 0, 0.5, 1, 2, 4 and 6Gy were employed. The irradiation field was shifted and laterally enlarged, to compensate for the beam deflection due to the magnetic field and ensure consistent and homogenous irradiations of the flasks. The human cancer cell lines SKMel (Melanoma) and SW1353 (chondrosarcoma) were selected which represent a high and a low (α/β) ratio cell type. Cell survival curves were generated applying a linear-quadratic curve fit, DNA damage and DNA damage clearance were assessed via γH2AX foci quantification at 1 and 24h post radiation treatment.

Results: Without a magnetic field, RBE values of 1.04±0.03 (SW1353) and 1.51±0.06 (SKMel) as well as RBE values of 0.93±0.15 (SW1353) and 2.28±0.40 (SKMel) were calculated for protons. Carbon treatments yielded RBE values of 1.68±0.04 (SW1353) and 2.30±0.07 (SKMel) and RBE values of 2.19±0.24 (SW1353) and 4.06±0.33 (SKMel). For a field strength of B=1T, RBE values of 1.06±0.03 (SW1353) and 1.47±0.06 (SKMel) resulted from protons, while RBE values of 1.70±0.05 (SW1353) and 2.37±0.08 (SKMel) were obtained for carbon ions. RBE values were calculated to be 1.06±0.12 (SW1353) and 2.33±0.40 (SKMel) following protons and 2.13±0.25 (SW1353) and 4.29±0.35 (SKMel) following carbon treatments. Substantially increased γH2AX foci per nucleus were found in both cell lines 1h after radiation with both ion species. At the 24h time point only carbon treated samples of both cell lines showed increased γH2AX levels. The presence of the magnetic field did neither influence the survival parameters of either cell line, nor initial DNA damage and DNA damage clearance.

Conclusions: Applying a perpendicular magnetic field did not influence the cell survival, DNA repair, nor the biological effectiveness of protons or carbon ions in two human cancer cell lines.
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http://dx.doi.org/10.1016/j.zemedi.2021.11.001DOI Listing
January 2022

Can Generative Adversarial Networks help to overcome the limited data problem in segmentation?

Z Med Phys 2021 Dec 17. Epub 2021 Dec 17.

Department of Radiation Oncology, Medical University of Vienna, Vienna, Austria; Competence Center for Preclinical Imaging and Biomedical Engineering, University of Applied Sciences Wiener Neustadt, Austria; Faculty of Engineering, University of Applied Sciences Wiener Neustadt, Austria.

Purpose: For image translational tasks, the application of deep learning methods showed that Generative Adversarial Network (GAN) architectures outperform the traditional U-Net networks, when using the same training data size. This study investigates whether this performance boost can also be expected for segmentation tasks with small training dataset size.

Materials/methods: Two models were trained on varying training dataset sizes ranging from 1-100 patients: a) U-Net and b) U-Net with patch discriminator (conditional GAN). The performance of both models to segment the male pelvis on CT-data was evaluated (Dice similarity coefficient, Hausdorff) with respect to training data size.

Results: No significant differences were observed between the U-Net and cGAN when the models were trained with the same training sizes up to 100 patients. The training dataset size had a significant impact on the models' performances, with vast improvements when increasing dataset sizes from 1 to 20 patients.

Conclusion: When introducing GANs for the segmentation task no significant performance boost was observed in our experiments, even in segmentation models developed on small datasets.
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http://dx.doi.org/10.1016/j.zemedi.2021.11.006DOI Listing
December 2021

An MRI sequence independent convolutional neural network for synthetic head CT generation in proton therapy.

Z Med Phys 2021 Dec 14. Epub 2021 Dec 14.

Medical University of Vienna, Department of Radiation Oncology, Vienna, Austria; MedAustron Ion Therapy Center, Wiener Neustadt, Austria. Electronic address:

A magnetic resonance imaging (MRI) sequence independent deep learning technique was developed and validated to generate synthetic computed tomography (sCT) scans for MR guided proton therapy. 47 meningioma patients previously undergoing proton therapy based on pencil beam scanning were divided into training (33), validation (6), and test (8) cohorts. T, T, and contrast enhanced T (T1CM) MRI sequences were used in combination with the planning CT (pCT) data to train a 3D U-Net architecture with ResNet-Blocks. A hyperparameter search was performed including two loss functions, two group sizes of normalisation, and depth of the network. Training outcome was compared between models trained for each individual MRI sequence and for all sequences combined. The performance was evaluated based on a metric and dosimetric analysis as well as spot difference maps. Furthermore, the influence of immobilisation masks that are not visible on MRIs was investigated. Based on the hyperparameter search, the final model was trained with fixed features per group for the group normalisation, six down-convolution steps, an input size of 128×192×192, and feature loss. For the test dataset for body/bone the mean absolute error (MAE) values were on average 79.8/216.3Houndsfield unit (HU) when trained using T1 images, 71.1/186.1HU for T2, and 82.9/236.4HU for T1CM. The structural similarity metric (SSIM) ranged from 0.95 to 0.98 for all sequences. The investigated dose parameters of the target structures agreed within 1% between original proton treatment plans and plans recalculated on sCTs. The spot difference maps had peaks at ±0.2cm and for 98% of all spots the difference was less than 1cm. A novel MRI sequence independent sCT generator was developed, which suggests that the training phase of neural networks can be disengaged from specific MRI acquisition protocols. In contrast to previous studies, the patient cohort consisted exclusively of actual proton therapy patients (i.e. "real-world data").
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http://dx.doi.org/10.1016/j.zemedi.2021.10.003DOI Listing
December 2021

Activation of efficient DNA repair mechanisms after photon and proton irradiation of human chondrosarcoma cells.

Sci Rep 2021 12 16;11(1):24116. Epub 2021 Dec 16.

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

Although particle therapy with protons has proven to be beneficial in the treatment of chondrosarcoma compared to photon-based (X-ray) radiation therapy, the cellular and molecular mechanisms have not yet been sufficiently investigated. Cell viability and colony forming ability were analyzed after X-ray and proton irradiation (IR). Cell cycle was analyzed using flow cytometry and corresponding regulator genes and key players of the DNA repair mechanisms were measured using next generation sequencing, protein expression and immunofluorescence staining. Changes in metabolic phenotypes were determined with nuclear magnetic resonance spectroscopy. Both X-ray and proton IR resulted in reduced cell survival and a G2/M phase arrest of the cell cycle. Especially 1 h after IR, a significant dose-dependent increase of phosphorylated γH2AX foci was observed. This was accompanied with a reprogramming in cellular metabolism. Interestingly, within 24 h the majority of clearly visible DNA damages were repaired and the metabolic phenotype restored. Involved DNA repair mechanisms are, besides the homology directed repair (HDR) and the non-homologous end-joining (NHEJ), especially the mismatch mediated repair (MMR) pathway with the key players EXO1, MSH3, and PCNA. Chondrosarcoma cells regenerates the majority of DNA damages within 24 h. These molecular mechanisms represent an important basis for an improved therapy.
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http://dx.doi.org/10.1038/s41598-021-03529-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8677811PMC
December 2021

Technical note: Experimental determination of the effective point of measurement of the PTW-31010 ionization chamber in proton and carbon ion beams.

Med Phys 2022 Jan 15;49(1):675-681. Epub 2021 Dec 15.

MedAustron Ion Therapy Center, Wiener Neustadt, Austria.

Purpose: The accurate knowledge of the effective point of measurement (P ) is particularly important for measurements in proximity to high dose gradients such as in the distal fall-off of particle beams. For plane-parallel ionization chambers (ICs), P is well known and located at the center of the inner surface of the entrance window. For cylindrical ICs, P is shifted from the chamber's center toward the beam source. According to IAEA TRS-398, this shift can be calculated as 0.75·r for light ions with r being the radius of the cavity. For proton beams and in absence of a dose gradient, no shift is recommended. We have experimentally determined P for the 0.125 cc Semiflex IC in both proton and carbon ion beams.

Methods: The first method consisted of simultaneous irradiation of a plane-parallel IC and the Semiflex in a 4-cm wide spread-out Bragg peak. In the second method, a single-energy beam was used, and both ICs were positioned successively at the same measurement depths. For both approaches, the shift of the distal edge of the depth ionization distributions recorded by the two chambers at different reference points was used to calculate P of the Semiflex. Both methods were applied in carbon ion beams, and only the latter was applied in proton beams.

Results: Both methods yielded a similar P for carbon ions, 0.88·r , and 0.84·r , which results in a difference of only 0.1 mm. The difference to the recommended value of 0.75·r is 0.4 and 0.3 mm, respectively, which is larger than the positioning uncertainty. In the proton beam, a P of 0.92·r was obtained.

Conclusions: The P for the 0.125 cc Semiflex IC is shifted further from the cavity center as recommended by IAEA TRS-398 for light ions, with the shift for proton beams being even larger than for carbon ion beams.
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http://dx.doi.org/10.1002/mp.15377DOI Listing
January 2022

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

Med Phys 2021 Nov 23;48(11):7333-7345. Epub 2021 Sep 23.

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

Purpose: This work presents the validation of an analytical pencil beam dose calculation algorithm in a commercial treatment planning system (TPS) for carbon ions by measurements of dose distributions in heterogeneous phantom geometries. Additionally, a comparison study of carbon ions versus protons is performed considering current best solutions in commercial TPS.

Methods: All treatment plans were optimized and calculated using the RayStation TPS (RaySearch, Sweden). The dose distributions calculated with the TPS were compared with measurements using a 24-pinpoint ionization chamber array (T31015, PTW, Germany). Tissue-like inhomogeneities (bone, lung, and soft tissue) were embedded in water, while a target volume of 4 x 4 x 4 cm was defined at two different depths behind the heterogeneities. In total, 10 different test cases, with and without range shifter as well as different air gaps, were investigated. Dose distributions inside as well as behind the target volume were evaluated.

Results: Inside the target volume, the mean dose difference between calculations and measurements, averaged over all test cases, was 1.6% for carbon ions. This compares well to the final agreement of 1.5% obtained in water at the commissioning stage of the TPS for carbon ions and is also within the clinically acceptable interval of 3%. The mean dose difference and maximal dose difference obtained outside the target area were 1.8% and 13.4%, respectively. The agreement of dose distributions for carbon ions in the target volumes was comparable or better to that between Monte Carlo (MC) dose calculations and measurements for protons. Percentage dose differences of more than 10% were present outside the target area behind bone-lung structures, where the carbon ion calculations systematically over predicted the dose. MC dose calculations for protons were superior to carbon ion beams outside the target volumes.

Conclusion: The pencil beam dose calculations for carbon ions in RayStation were found to be in good agreement with dosimetric measurements in heterogeneous geometries for points of interest located within the target. Large local discrepancies behind the target may contribute to incorrect dose predictions for organs at risk.
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http://dx.doi.org/10.1002/mp.15209DOI Listing
November 2021

Reply to comment on 'Lateral response heterogeneity of Bragg peak ionization chambers for narrow-beam photon and proton dosimetry'.

Phys Med Biol 2021 08 2;66(16). Epub 2021 Aug 2.

MedAustron Ion Therapy Center, Wiener Neustadt, Austria.

Gomà (2020) commented on our paper '' (Kuess20179189-206) which describes a method to determine the response pattern of large-area ionization chambers using a collimated x-ray beam. Gomà performed a simple Monte Carlo simulation to investigate the energy transferred by secondary electrons within the detector, deducing that our conclusion, that the chamber has a non-uniform response, is not supported by our results. We appreciate the work performed by Gomà very much and believe that the transport of secondary electrons in the chamber is an important contribution to understand the non-uniformity response of large-area chambers in narrow beams. However, we disagree with the conclusions drawn by Gomà that the radial response is homogenous. His simulation actually demonstrates that the response is non-uniform in an x-ray beam.
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http://dx.doi.org/10.1088/1361-6560/ac16bfDOI Listing
August 2021

Report of AAPM Task Group 219 on independent calculation-based dose/MU verification for IMRT.

Med Phys 2021 Oct 29;48(10):e808-e829. Epub 2021 Jul 29.

Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA, USA.

Independent verification of the dose per monitor unit (MU) to deliver the prescribed dose to a patient has been a mainstay of radiation oncology quality assurance (QA). We discuss the role of secondary dose/MU calculation programs as part of a comprehensive QA program. This report provides guidelines on calculation-based dose/MU verification for intensity modulated radiation therapy (IMRT) or volumetric modulated arc therapy (VMAT) provided by various modalities. We provide a review of various algorithms for "independent/second check" of monitor unit calculations for IMRT/VMAT. The report makes recommendations on the clinical implementation of secondary dose/MU calculation programs; on commissioning and acceptance of various commercially available secondary dose/MU calculation programs; on benchmark QA and periodic QA; and on clinically reasonable action levels for agreement of secondary dose/MU calculation programs.
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http://dx.doi.org/10.1002/mp.15069DOI Listing
October 2021

Professional practice changes in radiotherapy physics during the COVID-19 pandemic.

Phys Imaging Radiat Oncol 2021 Jul 22;19:25-32. Epub 2021 Jun 22.

European Society for Radiotherapy and Oncology (ESTRO), Physics Committee, Brussels, Belgium.

Background And Purpose: The COVID-19 pandemic has imposed changes in radiotherapy (RT) departments worldwide. Medical physicists (MPs) are key healthcare professionals in maintaining safe and effective RT. This study reports on MPs experience during the first pandemic peak and explores the consequences on their work.

Methods: A 39-question survey on changes in departmental and clinical practice and on the impact for the future was sent to the global MP community. A total of 433 responses were analysed by professional role and by country clustered on the daily infection numbers.

Results: The impact of COVID-19 was bigger in countries with high daily infection rate. The majority of MPs worked in alternation at home/on-site. Among practice changes, implementation and/or increased use of hypofractionation was the most common (47% of the respondents). Sixteen percent of respondents modified patient-specific quality assurance (QA), 21% reduced machine QA, and 25% moved machine QA to weekends/evenings. The perception of trust in leadership and team unity was reversed between management MPs (towards increased trust and unity) and clinical MPs (towards a decrease). Changes such as home-working and increased use of hypofractionation were welcomed. However, some MPs were concerned about pressure to keep negative changes (e.g. weekend work).

Conclusion: COVID-19 affected MPs through changes in practice and QA procedures but also in terms of trust in leadership and team unity. Some changes were welcomed but others caused worries for the future. This report forms the basis, from a medical physics perspective, to evaluate long-lasting changes within a multi-disciplinary setting.
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http://dx.doi.org/10.1016/j.phro.2021.06.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8216850PMC
July 2021

Technical Note: Dose prediction for radiation therapy using feature-based losses and One Cycle Learning.

Med Phys 2021 Sep 22;48(9):5562-5566. Epub 2021 Jun 22.

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

Purpose: To present the technical details of the runner-up model in the open knowledge-based planning (OpenKBP) challenge for the dose-volume histogram (DVH) stream. The model was designed to ensure simple and reproducible training, without the necessity of costly advanced generative adversarial network (GAN) techniques.

Methods: The model was developed based on the OpenKBP challenge dataset, consisting of 200 and 40 head-and-neck patients for training and validation, respectively. The final model is a U-Net with additional ResNet blocks between up- and down convolutions. The results were obtained by training the model with AdamW with the One Cycle scheduler. The loss function is a combination of the L1 loss with a feature loss, which uses a pretrained video classifier as a feature extractor. The performance was evaluated on another 100 patients in the OpenKBP test dataset. The DVH metrics of the test data were evaluated, where , and were calculated for the organs at risk (OARs) and , , and were computed for the target structures. DVH metric differences between predicted and true dose are reported in percentage.

Results: The model achieved 2nd and 4th place in the DVH and dose stream of the OpenKBP challenge, respectively. The dose and DVH score were 2.62 ± 1.10 and 1.52 ± 1.06, respectively. Mean dose differences for the different structures and DVH parameters were within ±1%.

Conclusion: This straightforward approach produced excellent results. It incorporated One Cycle Learning, ResNet, and feature-based losses, which are common computer vision techniques.
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http://dx.doi.org/10.1002/mp.14774DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8518421PMC
September 2021

Cone beam CT based validation of neural network generated synthetic CTs for radiotherapy in the head region.

Med Phys 2021 Aug 28;48(8):4560-4571. Epub 2021 Jun 28.

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

Purpose: In the past years, many different neural network-based conversion techniques for synthesizing computed tomographys (sCTs) from MR images have been published. While the model's performance can be checked during the training against the test set, test datasets can never represent the whole population. Conversion errors can still occur for special cases, for example, for unusual anatomical situations. Therefore, the performance of sCT conversion needs to be verified on a patient specific level, especially in the absence of a planning CT (pCT). In this study, the capability of cone-beam CTs (CBCTs) for the validation of sCTs generated by a neural network was investigated.

Methods: 41 patients with tumors in the head region were selected. 20 of them were used for model training and 10 for validation. Different implementations of CycleGAN (with/without identity and feature loss) were used to generate sCTs. The pixel (MAE, RMSE, PSNR) and geometric error (DICE, Sensitivity, Specificity) values were reported to identify the best model. VMAT plans were created for the remaining 11 patients on the pCTs. These plans were re-calculated on sCTs and CBCTs. An automatic density overriding method ( ) and a population-based dose calculation method ( ) were employed for CBCT-based dose calculation. The dose distributions were analysed using 3D global gamma analysis, applying a threshold of 10% with respect to the prescribed dose. Differences in DVH metrics for the PTV and the organs-at-risk were compared among the dose distributions based on pCTs, sCTs, and CBCTs.

Results: The best model was the CycleGAN without identity and feature matching loss. Including the identity loss led to a metric decrease of 10% for DICE and a metric increase of 20-60 HU for MAE. Using the 2%/2 mm gamma criterion and pCT as reference, the mean gamma pass rates were 99.0   0.4% for sCTs. Mean gamma pass rate values comparing pCT and CBCT were 99.0   0.8% and 99.1   0.8% for the and , respectively. The mean gamma pass rates comparing sCT and CBCT resulted in 98.4   1.6% and 99.2   0.6% for and , respectively. The differences between the gamma-pass-rates of the sCT and two CBCT-based methods were not significant. The majority of deviations of the investigated DVH metrices between sCTs and CBCTs were within 2%.

Conclusion: The dosimetric results demonstrate good agreement between sCT, CBCT, and pCT based calculations. A properly applied CBCT conversion method can serve as a tool for quality assurance procedures in an MR only radiotherapy workflow for head patients. Dosimetric deviations of DVH metrics between sCT and CBCTs of larger than 2% should be followed up. A systematic shift of approximately 1% should be taken into account when using the approach in an MR only workflow.
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http://dx.doi.org/10.1002/mp.14987DOI Listing
August 2021

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 Jun 30;197(6):505-519. 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
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8154798PMC
June 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 2021 May 3;48(5):2572-2579. Epub 2021 Apr 3.

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
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8251909PMC
May 2021

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

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
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