@article{TamihardjaRazinskasExneretal.2021, author = {Tamihardja, J{\"o}rg and Razinskas, Gary and Exner, Florian and Richter, Anne and Kessler, Patrick and Weick, Stefan and Kraft, Johannes and Mantel, Frederick and Flentje, Michael and Polat, B{\"u}lent}, title = {Comparison of treatment plans for hypofractionated high-dose prostate cancer radiotherapy using the Varian Halcyon and the Elekta Synergy platforms}, series = {Journal of Applied Clinical Medical Physics}, volume = {22}, journal = {Journal of Applied Clinical Medical Physics}, number = {9}, doi = {10.1002/acm2.13380}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-260722}, pages = {262-270}, year = {2021}, abstract = {Purpose To compare radiotherapy plans between an O-ring and a conventional C-arm linac for hypofractionated high-dose prostate radiotherapy in terms of plan quality, dose distribution, and quality assurance in a multi-vendor environment. Methods Twenty prostate cancer treatment plans were irradiated on the O-ring Varian Halcyon linac and were re-optimized for the C-arm Elekta Synergy Agility linac. Dose-volume histogram metrics for target coverage and organ at risk dose, quality assurance, and monitor units were retrospectively compared. Patient-specific quality assurance with ion chamber measurements, gamma index analysis, and portal dosimetry was performed using the Varian Portal Dosimetry system and the ArcCHECK® phantom (Sun Nuclear Corporation). Prostate-only radiotherapy was delivered with simultaneous integrated boost (SIB) volumetric modulated arc therapy (VMAT) in 20 fractions of 2.5/3.0 Gy each. Results For both linacs, target coverage was excellent and plan quality comparable. Homogeneity in PTVBoost was high for Synergy as well as Halcyon with a mean homogeneity index of 0.07 ± 0.01 and 0.05 ± 0.01, respectively. Mean dose for the organs at risk rectum and bladder differed not significantly between the linacs but were higher for the femoral heads and penile bulb for Halcyon. Quality assurance showed no significant differences in terms of ArcCHECK gamma pass rates. Median pass rate for 3\%/2 mm was 99.3\% (96.7 to 99.8\%) for Synergy and 99.8\% (95.6 to 100\%) for Halcyon. Agreement between calculated and measured dose was high with a median deviation of -0.6\% (-1.7 to 0.8\%) for Synergy and 0.2\% (-0.6 to 2.3\%) for Halcyon. Monitor units were higher for the Halcyon by approximately 20\% (p < 0.001). Conclusion Hypofractionated high-dose prostate cancer SIB VMAT on the Halcyon system is feasible with comparable plan quality in reference to a standard C-arm Elekta Synergy linac.}, language = {en} } @article{TamihardjaCirsiKessleretal.2021, author = {Tamihardja, J{\"o}rg and Cirsi, Sinan and Kessler, Patrick and Razinskas, Gary and Exner, Florian and Richter, Anne and Polat, B{\"u}lent and Flentje, Michael}, title = {Cone beam CT-based dose accumulation and analysis of delivered dose to the dominant intraprostatic lesion in primary radiotherapy of prostate cancer}, series = {Radiation Oncology}, volume = {16}, journal = {Radiation Oncology}, doi = {10.1186/s13014-021-01933-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265656}, year = {2021}, abstract = {Background Evaluation of delivered dose to the dominant intraprostatic lesion (DIL) for moderately hypofractionated radiotherapy of prostate cancer by cone beam computed tomography (CBCT)-based dose accumulation and target coverage analysis. Methods Twenty-three patients with localized prostate cancer treated with moderately hypofractionated prostate radiotherapy with simultaneous integrated boost (SIB) between December 2016 and February 2020 were retrospectively analyzed. Included patients were required to have an identifiable DIL on bi-parametric planning magnetic resonance imaging (MRI). After import into the RayStation treatment planning system and application of a step-wise density override, the fractional doses were computed on each CBCT and were consecutively mapped onto the planning CT via a deformation vector field derived from deformable image registration. Fractional doses were accumulated for all CBCTs and interpolated for missing CBCTs, resulting in the delivered dose for PTV\(_{DIL}\), PTV\(_{Boost}\), PTV, and the organs at risk. The location of the index lesions was recorded according to the sector map of the Prostate Imaging Reporting and Data System (PIRADS) Version 2.1. Target coverage of the index lesions was evaluated and stratified for location. Results In total, 338 CBCTs were available for analysis. Dose accumulation target coverage of PTV\(_{DIL}\), PTV\(_{Boost}\), and PTV was excellent and no cases of underdosage in D\(_{Mean}\), D_95\%, D_02\%, and D_98\% could be detected. Delivered rectum D\(_{Mean}\) did not significantly differ from the planned dose. Bladder mean DMean was higher than planned with 19.4 ± 7.4 Gy versus 18.8 ± 7.5 Gy, p < 0.001. The penile bulb showed a decreased delivered mean DMean with 29.1 ± 14.0 Gy versus 29.8 ± 14.4 Gy, p < 0.001. Dorsal DILs, defined as DILs in the posterior medial peripheral zone of the prostate, showed a significantly lower delivered dose with a mean DMean difference of 2.2 Gy (95\% CI 1.3-3.1 Gy, p < 0.001) compared to ventral lesions. Conclusions CBCT-based dose accumulation showed an adequate delivered dose to the dominant intraprostatic lesion and organs at risk within planning limits. Cautious evaluation of the target coverage for index lesions adjacent to the rectum is warranted to avoid underdosage.}, language = {en} } @article{RichterWeickKriegeretal.2017, author = {Richter, Anne and Weick, Stefan and Krieger, Thomas and Exner, Florian and Kellner, Sonja and Polat, B{\"u}lent and Flentje, Michael}, title = {Evaluation of a software module for adaptive treatment planning and re-irradiation}, series = {Radiation Oncology}, volume = {12}, journal = {Radiation Oncology}, number = {205}, doi = {10.1186/s13014-017-0943-4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158711}, year = {2017}, abstract = {Background: The aim of this work is to validate the Dynamic Planning Module in terms of usability and acceptance in the treatment planning workflow. Methods: The Dynamic Planning Module was used for decision making whether a plan adaptation was necessary within one course of radiation therapy. The Module was also used for patients scheduled for re-irradiation to estimate the dose in the pretreated region and calculate the accumulated dose to critical organs at risk. During one year, 370 patients were scheduled for plan adaptation or re-irradiation. All patient cases were classified according to their treated body region. For a sub-group of 20 patients treated with RT for lung cancer, the dosimetric effect of plan adaptation during the main treatment course was evaluated in detail. Changes in tumor volume, frequency of re-planning and the time interval between treatment start and plan adaptation were assessed. Results: The Dynamic Planning Tool was used in 20\% of treated patients per year for both approaches nearly equally (42\% plan adaptation and 58\% re-irradiation). Most cases were assessed for the thoracic body region (51\%) followed by pelvis (21\%) and head and neck cases (10\%). The sub-group evaluation showed that unintended plan adaptation was performed in 38\% of the scheduled cases. A median time span between first day of treatment and necessity of adaptation of 17 days (range 4-35 days) was observed. PTV changed by 12 ± 12\% on average (maximum change 42\%). PTV decreased in 18 of 20 cases due to tumor shrinkage and increased in 2 of 20 cases. Re-planning resulted in a reduction of the mean lung dose of the ipsilateral side in 15 of 20 cases. Conclusion: The experience of one year showed high acceptance of the Dynamic Planning Module in our department for both physicians and medical physicists. The re-planning can potentially reduce the accumulated dose to the organs at risk and ensure a better target volume coverage. In the re-irradiation situation, the Dynamic Planning Tool was used to consider the pretreatment dose, to adapt the actual treatment schema more specifically and to review the accumulated dose.}, language = {en} } @article{RichterExnerBratengeieretal.2019, author = {Richter, Anne and Exner, Florian and Bratengeier, Klaus and Polat, B{\"u}lent and Flentje, Michael and Weick, Stefan}, title = {Impact of beam configuration on VMAT plan quality for Pinnacle\(^3\)Auto-Planning for head and neck cases}, series = {Radiation Oncology}, volume = {14}, journal = {Radiation Oncology}, doi = {10.1186/s13014-019-1211-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-200301}, pages = {12}, year = {2019}, abstract = {Background The purpose of this study was to compare automatically generated VMAT plans to find the superior beam configurations for Pinnacle3 Auto-Planning and share "best practices". Methods VMAT plans for 20 patients with head and neck cancer were generated using Pinnacle3 Auto-Planning Module (Pinnacle3 Version 9.10) with different beam setup parameters. VMAT plans for single (V1) or double arc (V2) and partial or full gantry rotation were optimized. Beam configurations with different collimator positions were defined. Target coverage and sparing of organs at risk were evaluated based on scoring of an evaluation parameter set. Furthermore, dosimetric evaluation was performed based on the composite objective value (COV) and a new cross comparison method was applied using the COVs. Results The evaluation showed a superior plan quality for double arcs compared to one single arc or two single arcs for all cases. Plan quality was superior if a full gantry rotation was allowed during optimization for unilateral target volumes. A double arc technique with collimator setting of 15° was superior to a double arc with collimator 60° and a two single arcs with collimator setting of 15° and 345°. Conclusion The evaluation showed that double and full arcs are superior to single and partial arcs in terms of organs at risk sparing even for unilateral target volumes. The collimator position was found as an additional setup parameter, which can further improve the target coverage and sparing of organs at risk.}, language = {en} } @article{RichterPolatLawrenzetal.2016, author = {Richter, Anne and Polat, B{\"u}lent and Lawrenz, Ingulf and Weick, Stefan and Sauer, Otto and Flentje, Michael and Mantel, Frederick}, title = {Initial results for patient setup verification using transperineal ultrasound and cone beam CT in external beam radiation therapy of prostate cancer}, series = {Radiation Oncology}, volume = {11}, journal = {Radiation Oncology}, number = {147}, doi = {10.1186/s13014-016-0722-7}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-147677}, year = {2016}, abstract = {Evaluation of set up error detection by a transperineal ultrasound in comparison with a cone beam CT (CBCT) based system in external beam radiation therapy (EBRT) of prostate cancer. Methods: Setup verification was performed with transperineal ultrasound (TPUS) and CBCT for 10 patients treated with EBRT for prostate cancer. In total, 150 ultrasound and CBCT scans were acquired in rapid succession and analyzed for setup errors. The deviation between setup errors of the two modalities was evaluated separately for each dimension. Results: A moderate correlation in lateral, vertical and longitudinal direction was observed comparing the setup errors. Mean differences between TPUS and CBCT were (-2.7 ± 2.3) mm, (3.0 ± 2.4) mm and (3.2 ± 2.7) mm in lateral, vertical and longitudinal direction, respectively. The mean Euclidean difference between TPUS and CBCT was (6.0 ± 3.1) mm. Differences up to 19.2 mm were observed between the two imaging modalities. Discrepancies between TPUS and CBCT of at least 5 mm occurred in 58 \% of monitored treatment sessions. Conclusion: Setup differences between TPUS and CBCT are 6 mm on average. Although the correlation of the setup errors determined by the two different image modalities is rather week, the combination of setup verification by CBCT and intrafraction motion monitoring by TPUS imaging can use the benefits of both imaging modalities.}, language = {en} } @article{WeickBreuerRichteretal.2020, author = {Weick, Stefan and Breuer, Kathrin and Richter, Anne and Exner, Florian and Str{\"o}hle, Serge-Peer and Lutyj, Paul and Tamihardja, J{\"o}rg and Veldhoen, Simon and Flentje, Michael and Polat, B{\"u}lent}, title = {Non-rigid image registration of 4D-MRI data for improved delineation of moving tumors}, series = {BMC Medical Imaging}, volume = {20}, journal = {BMC Medical Imaging}, doi = {10.1186/s12880-020-00439-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-229271}, year = {2020}, abstract = {Background To increase the image quality of end-expiratory and end-inspiratory phases of retrospective respiratory self-gated 4D MRI data sets using non-rigid image registration for improved target delineation of moving tumors. Methods End-expiratory and end-inspiratory phases of volunteer and patient 4D MRI data sets are used as targets for non-rigid image registration of all other phases using two different registration schemes: In the first, all phases are registered directly (dir-Reg) while next neighbors are successively registered until the target is reached in the second (nn-Reg). Resulting data sets are quantitatively compared using diaphragm and tumor sharpness and the coefficient of variation of regions of interest in the lung, liver, and heart. Qualitative assessment of the patient data regarding noise level, tumor delineation, and overall image quality was performed by blinded reading based on a 4 point Likert scale. Results The median coefficient of variation was lower for both registration schemes compared to the target. Median dir-Reg coefficient of variation of all ROIs was 5.6\% lower for expiration and 7.0\% lower for inspiration compared with nn-Reg. Statistical significant differences between the two schemes were found in all comparisons. Median sharpness in inspiration is lower compared to expiration sharpness in all cases. Registered data sets were rated better compared to the targets in all categories. Over all categories, mean expiration scores were 2.92 +/- 0.18 for the target, 3.19 +/- 0.22 for nn-Reg and 3.56 +/- 0.14 for dir-Reg and mean inspiration scores 2.25 +/- 0.12 for the target, 2.72 +/- 215 0.04 for nn-Reg and 3.78 +/- 0.04 for dir-Reg. Conclusions In this work, end-expiratory and inspiratory phases of a 4D MRI data sets are used as targets for non-rigid image registration of all other phases. It is qualitatively and quantitatively shown that image quality of the targets can be significantly enhanced leading to improved target delineation of moving tumors.}, language = {en} } @article{BliziotisKluijtmansTinneveltetal.2022, author = {Bliziotis, Nikolaos G. and Kluijtmans, Leo A. J. and Tinnevelt, Gerjen H. and Reel, Parminder and Reel, Smarti and Langton, Katharina and Robledo, Mercedes and Pamporaki, Christina and Pecori, Alessio and Van Kralingen, Josie and Tetti, Martina and Engelke, Udo F. H. and Erlic, Zoran and Engel, Jasper and Deutschbein, Timo and N{\"o}lting, Svenja and Prejbisz, Aleksander and Richter, Susan and Adamski, Jerzy and Januszewicz, Andrzej and Ceccato, Filippo and Scaroni, Carla and Dennedy, Michael C. and Williams, Tracy A. and Lenzini, Livia and Gimenez-Roqueplo, Anne-Paule and Davies, Eleanor and Fassnacht, Martin and Remde, Hanna and Eisenhofer, Graeme and Beuschlein, Felix and Kroiss, Matthias and Jefferson, Emily and Zennaro, Maria-Christina and Wevers, Ron A. and Jansen, Jeroen J. and Deinum, Jaap and Timmers, Henri J. L. M.}, title = {Preanalytical pitfalls in untargeted plasma nuclear magnetic resonance metabolomics of endocrine hypertension}, series = {Metabolites}, volume = {12}, journal = {Metabolites}, number = {8}, issn = {2218-1989}, doi = {10.3390/metabo12080679}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-282930}, year = {2022}, abstract = {Despite considerable morbidity and mortality, numerous cases of endocrine hypertension (EHT) forms, including primary aldosteronism (PA), pheochromocytoma and functional paraganglioma (PPGL), and Cushing's syndrome (CS), remain undetected. We aimed to establish signatures for the different forms of EHT, investigate potentially confounding effects and establish unbiased disease biomarkers. Plasma samples were obtained from 13 biobanks across seven countries and analyzed using untargeted NMR metabolomics. We compared unstratified samples of 106 PHT patients to 231 EHT patients, including 104 PA, 94 PPGL and 33 CS patients. Spectra were subjected to a multivariate statistical comparison of PHT to EHT forms and the associated signatures were obtained. Three approaches were applied to investigate and correct confounding effects. Though we found signatures that could separate PHT from EHT forms, there were also key similarities with the signatures of sample center of origin and sample age. The study design restricted the applicability of the corrections employed. With the samples that were available, no biomarkers for PHT vs. EHT could be identified. The complexity of the confounding effects, evidenced by their robustness to correction approaches, highlighted the need for a consensus on how to deal with variabilities probably attributed to preanalytical factors in retrospective, multicenter metabolomics studies.}, language = {en} } @article{ViljurAbellaAdameketal.2022, author = {Viljur, Mari-Liis and Abella, Scott R. and Ad{\´a}mek, Martin and Alencar, Janderson Batista Rodrigues and Barber, Nicholas A. and Beudert, Burkhard and Burkle, Laura A. and Cagnolo, Luciano and Campos, Brent R. and Chao, Anne and Chergui, Brahim and Choi, Chang-Yong and Cleary, Daniel F. R. and Davis, Thomas Seth and Dechnik-V{\´a}zquez, Yanus A. and Downing, William M. and Fuentes-Ramirez, Andr{\´e}s and Gandhi, Kamal J. K. and Gehring, Catherine and Georgiev, Kostadin B. and Gimbutas, Mark and Gongalsky, Konstantin B. and Gorbunova, Anastasiya Y. and Greenberg, Cathryn H. and Hylander, Kristoffer and Jules, Erik S. and Korobushkin, Daniil I. and K{\"o}ster, Kajar and Kurth, Valerie and Lanham, Joseph Drew and Lazarina, Maria and Leverkus, Alexandro B. and Lindenmayer, David and Marra, Daniel Magnabosco and Mart{\´i}n-Pinto, Pablo and Meave, Jorge A. and Moretti, Marco and Nam, Hyun-Young and Obrist, Martin K. and Petanidou, Theodora and Pons, Pere and Potts, Simon G. and Rapoport, Irina B. and Rhoades, Paul R. and Richter, Clark and Saifutdinov, Ruslan A. and Sanders, Nathan J. and Santos, Xavier and Steel, Zachary and Tavella, Julia and Wendenburg, Clara and Wermelinger, Beat and Zaitsev, Andrey S. and Thorn, Simon}, title = {The effect of natural disturbances on forest biodiversity: an ecological synthesis}, series = {Biological Reviews}, volume = {97}, journal = {Biological Reviews}, number = {5}, doi = {10.1111/brv.12876}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-287168}, pages = {1930 -- 1947}, year = {2022}, abstract = {Disturbances alter biodiversity via their specific characteristics, including severity and extent in the landscape, which act at different temporal and spatial scales. Biodiversity response to disturbance also depends on the community characteristics and habitat requirements of species. Untangling the mechanistic interplay of these factors has guided disturbance ecology for decades, generating mixed scientific evidence of biodiversity responses to disturbance. Understanding the impact of natural disturbances on biodiversity is increasingly important due to human-induced changes in natural disturbance regimes. In many areas, major natural forest disturbances, such as wildfires, windstorms, and insect outbreaks, are becoming more frequent, intense, severe, and widespread due to climate change and land-use change. Conversely, the suppression of natural disturbances threatens disturbance-dependent biota. Using a meta-analytic approach, we analysed a global data set (with most sampling concentrated in temperate and boreal secondary forests) of species assemblages of 26 taxonomic groups, including plants, animals, and fungi collected from forests affected by wildfires, windstorms, and insect outbreaks. The overall effect of natural disturbances on α-diversity did not differ significantly from zero, but some taxonomic groups responded positively to disturbance, while others tended to respond negatively. Disturbance was beneficial for taxonomic groups preferring conditions associated with open canopies (e.g. hymenopterans and hoverflies), whereas ground-dwelling groups and/or groups typically associated with shady conditions (e.g. epigeic lichens and mycorrhizal fungi) were more likely to be negatively impacted by disturbance. Across all taxonomic groups, the highest α-diversity in disturbed forest patches occurred under moderate disturbance severity, i.e. with approximately 55\% of trees killed by disturbance. We further extended our meta-analysis by applying a unified diversity concept based on Hill numbers to estimate α-diversity changes in different taxonomic groups across a gradient of disturbance severity measured at the stand scale and incorporating other disturbance features. We found that disturbance severity negatively affected diversity for Hill number q = 0 but not for q = 1 and q = 2, indicating that diversity-disturbance relationships are shaped by species relative abundances. Our synthesis of α-diversity was extended by a synthesis of disturbance-induced change in species assemblages, and revealed that disturbance changes the β-diversity of multiple taxonomic groups, including some groups that were not affected at the α-diversity level (birds and woody plants). Finally, we used mixed rarefaction/extrapolation to estimate biodiversity change as a function of the proportion of forests that were disturbed, i.e. the disturbance extent measured at the landscape scale. The comparison of intact and naturally disturbed forests revealed that both types of forests provide habitat for unique species assemblages, whereas species diversity in the mixture of disturbed and undisturbed forests peaked at intermediate values of disturbance extent in the simulated landscape. Hence, the relationship between α-diversity and disturbance severity in disturbed forest stands was strikingly similar to the relationship between species richness and disturbance extent in a landscape consisting of both disturbed and undisturbed forest habitats. This result suggests that both moderate disturbance severity and moderate disturbance extent support the highest levels of biodiversity in contemporary forest landscapes.}, language = {en} } @article{BotheDeubelHesseetal.2019, author = {Bothe, Friederike and Deubel, Anne-Kathrin and Hesse, Eliane and Lotz, Benedict and Groll, J{\"u}rgen and Werner, Carsten and Richter, Wiltrud and Hagmann, Sebastien}, title = {Treatment of focal cartilage defects in minipigs with zonal chondrocyte/mesenchymal progenitor cell constructs}, series = {International Journal of Molecular Sciences}, volume = {20}, journal = {International Journal of Molecular Sciences}, number = {3}, issn = {1422-0067}, doi = {10.3390/ijms20030653}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-285118}, year = {2019}, abstract = {Despite advances in cartilage repair strategies, treatment of focal chondral lesions remains an important challenge to prevent osteoarthritis. Articular cartilage is organized into several layers and lack of zonal organization of current grafts is held responsible for insufficient biomechanical and biochemical quality of repair-tissue. The aim was to develop a zonal approach for cartilage regeneration to determine whether the outcome can be improved compared to a non-zonal strategy. Hydrogel-filled polycaprolactone (PCL)-constructs with a chondrocyte-seeded upper-layer deemed to induce hyaline cartilage and a mesenchymal stromal cell (MSC)-containing bottom-layer deemed to induce calcified cartilage were compared to chondrocyte-based non-zonal grafts in a minipig model. Grafts showed comparable hardness at implantation and did not cause visible signs of inflammation. After 6 months, X-ray microtomography (µCT)-analysis revealed significant bone-loss in both treatment groups compared to empty controls. PCL-enforcement and some hydrogel-remnants were retained in all defects, but most implants were pressed into the subchondral bone. Despite important heterogeneities, both treatments reached a significantly lower modified O'Driscoll-score compared to empty controls. Thus, PCL may have induced bone-erosion during joint loading and misplacement of grafts in vivo precluding adequate permanent orientation of zones compared to surrounding native cartilage.}, language = {en} } @article{KraftWeickBreueretal.2022, author = {Kraft, Johannes and Weick, Stefan and Breuer, Kathrin and Lutyj, Paul and Bratengeier, Klaus and Exner, Florian and Richter, Anne and Tamihardja, J{\"o}rg and Lisowski, Dominik and Polat, B{\"u}lent and Flentje, Michael}, title = {Treatment plan comparison for irradiation of multiple brain metastases with hippocampal avoidance whole brain radiotherapy and simultaneous integrated boost using the Varian Halcyon and the Elekta Synergy platforms}, series = {Radiation Oncology}, volume = {17}, journal = {Radiation Oncology}, doi = {10.1186/s13014-022-02156-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-301221}, year = {2022}, abstract = {No abstract available.}, language = {en} }