TY - JOUR A1 - Richter, Anne A1 - Weick, Stefan A1 - Krieger, Thomas A1 - Exner, Florian A1 - Kellner, Sonja A1 - Polat, Bülent A1 - Flentje, Michael T1 - Evaluation of a software module for adaptive treatment planning and re-irradiation JF - Radiation Oncology N2 - 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. KW - re-irradiation KW - lung cancer KW - adaptation KW - re-planning Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-158711 VL - 12 IS - 205 ER - TY - JOUR A1 - Richter, Anne A1 - Wegener, Sonja A1 - Breuer, Kathrin A1 - Razinskas, Gary A1 - Weick, Stefan A1 - Exner, Florian A1 - Bratengeier, Klaus A1 - Flentje, Michael A1 - Sauer, Otto A1 - Polat, Bülent T1 - Comparison of sliding window and field-in-field techniques for tangential whole breast irradiation using the Halcyon and Synergy Agility systems JF - Radiation Oncology N2 - Background To implement a tangential treatment technique for whole breast irradiation using the Varian Halcyon and to compare it with Elekta Synergy Agility plans. Methods For 20 patients two comparable treatment plans with respect to dose coverage and normal tissue sparing were generated. Tangential field-in-field treatment plans (Pinnacle/Synergy) were replanned using the sliding window technique (Eclipse/Halcyon). Plan specific QA was performed using the portal Dosimetry and the ArcCHECK phantom. Imaging and treatment dose were evaluated for treatment delivery on both systems using a modified CIRS Phantom. Results The mean number of monitor units for a fraction dose of 2.67 Gy was 515 MUs and 260 MUs for Halcyon and Synergy Agility plans, respectively. The homogeneity index and dose coverage were similar for both treatment units. The plan specific QA showed good agreement between measured and calculated plans. All Halcyon plans passed portal dosimetry QA (3%/2 mm) with 100% points passing and ArcCheck QA (3%/2 mm) with 99.5%. Measurement of the cumulated treatment and imaging dose with the CIRS phantom resulted in lower dose to the contralateral breast for the Halcyon plans. Conclusions For the Varian Halcyon a plan quality similar to the Elekta Synergy device was achieved. For the Halcyon plans the dose contribution from the treatment fields to the contralateral breast was even lower due to less interleaf transmission of the Halcyon MLC and a lower contribution of scattered dose from the collimator system. KW - whole breast irradiation KW - Halcyon KW - IGRT KW - dose to OARs Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-265704 VL - 16 ER - TY - JOUR A1 - Tamihardja, Jörg A1 - Cirsi, Sinan A1 - Kessler, Patrick A1 - Razinskas, Gary A1 - Exner, Florian A1 - Richter, Anne A1 - Polat, Bülent A1 - Flentje, Michael T1 - Cone beam CT-based dose accumulation and analysis of delivered dose to the dominant intraprostatic lesion in primary radiotherapy of prostate cancer JF - Radiation Oncology N2 - 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. KW - adaptive radiotherapy KW - deformable image registration KW - dominant intraprostatic lesion KW - dose accumulation KW - prostate cancer KW - prostate Imaging Reporting and Data System Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-265656 VL - 16 ER - TY - JOUR A1 - Richter, Anne A1 - Exner, Florian A1 - Bratengeier, Klaus A1 - Polat, Bülent A1 - Flentje, Michael A1 - Weick, Stefan T1 - Impact of beam configuration on VMAT plan quality for Pinnacle\(^3\)Auto-Planning for head and neck cases JF - Radiation Oncology N2 - 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. KW - auto-planning KW - VMAT KW - single arc KW - double arc KW - full arc KW - partial arc KW - plan comparison Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-200301 VL - 14 ER - TY - JOUR A1 - Weick, Stefan A1 - Breuer, Kathrin A1 - Richter, Anne A1 - Exner, Florian A1 - Ströhle, Serge-Peer A1 - Lutyj, Paul A1 - Tamihardja, Jörg A1 - Veldhoen, Simon A1 - Flentje, Michael A1 - Polat, Bülent T1 - Non-rigid image registration of 4D-MRI data for improved delineation of moving tumors JF - BMC Medical Imaging N2 - 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. KW - 4D-MRI KW - Non-rigid image registration KW - Radiotherapy treatment planning KW - Respiratory induced tumor motion Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-229271 VL - 20 ER - TY - JOUR A1 - Viljur, Mari‐Liis A1 - Abella, Scott R. A1 - Adámek, Martin A1 - Alencar, Janderson Batista Rodrigues A1 - Barber, Nicholas A. A1 - Beudert, Burkhard A1 - Burkle, Laura A. A1 - Cagnolo, Luciano A1 - Campos, Brent R. A1 - Chao, Anne A1 - Chergui, Brahim A1 - Choi, Chang‐Yong A1 - Cleary, Daniel F. R. A1 - Davis, Thomas Seth A1 - Dechnik‐Vázquez, Yanus A. A1 - Downing, William M. A1 - Fuentes‐Ramirez, Andrés A1 - Gandhi, Kamal J. K. A1 - Gehring, Catherine A1 - Georgiev, Kostadin B. A1 - Gimbutas, Mark A1 - Gongalsky, Konstantin B. A1 - Gorbunova, Anastasiya Y. A1 - Greenberg, Cathryn H. A1 - Hylander, Kristoffer A1 - Jules, Erik S. A1 - Korobushkin, Daniil I. A1 - Köster, Kajar A1 - Kurth, Valerie A1 - Lanham, Joseph Drew A1 - Lazarina, Maria A1 - Leverkus, Alexandro B. A1 - Lindenmayer, David A1 - Marra, Daniel Magnabosco A1 - Martín‐Pinto, Pablo A1 - Meave, Jorge A. A1 - Moretti, Marco A1 - Nam, Hyun‐Young A1 - Obrist, Martin K. A1 - Petanidou, Theodora A1 - Pons, Pere A1 - Potts, Simon G. A1 - Rapoport, Irina B. A1 - Rhoades, Paul R. A1 - Richter, Clark A1 - Saifutdinov, Ruslan A. A1 - Sanders, Nathan J. A1 - Santos, Xavier A1 - Steel, Zachary A1 - Tavella, Julia A1 - Wendenburg, Clara A1 - Wermelinger, Beat A1 - Zaitsev, Andrey S. A1 - Thorn, Simon T1 - The effect of natural disturbances on forest biodiversity: an ecological synthesis JF - Biological Reviews N2 - 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. KW - natural disturbance KW - diversity–disturbance relationship KW - disturbance severity KW - disturbance extent KW - intermediate disturbance hypothesis KW - forest communities KW - α‐diversity KW - β‐diversity Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-287168 VL - 97 IS - 5 SP - 1930 EP - 1947 ER - TY - JOUR A1 - Zimmermann, Marcus A1 - Richter, Anne A1 - Weick, Stefan A1 - Exner, Florian A1 - Mantel, Frederick A1 - Diefenhardt, Markus A1 - Fokas, Emmanouil A1 - Kosmala, Rebekka A1 - Flentje, Michael A1 - Polat, Bülent T1 - Acute toxicities of patients with locally advanced rectal cancer treated with intensified chemoradiotherapy within the CAO/ARO/AIO-12 trial: comparing conventional versus VMAT planning at a single center JF - Scientific Reports N2 - In locally advanced rectal cancer (LARC) neoadjuvant chemoradiotherapy is regarded as standard treatment. We assessed acute toxicities in patients receiving conventional 3D-conformal radiotherapy (3D-RT) and correlated them with dosimetric parameters after re-planning with volumetric modulated arc therapy (VMAT). Patients were randomized within the multicenter CAO/ARO/AIO-12 trial and received 50.4 Gy in 28 fractions and simultaneous chemotherapy with fluorouracil and oxaliplatin. Organs at risk (OAR) were contoured in a standardized approach. Acute toxicities and dose volume histogram parameters of 3D-RT plans were compared to retrospectively calculated VMAT plans. From 08/2015 to 01/2018, 35 patients with LARC were treated at one study center. Thirty-four patients were analyzed of whom 1 (3%) was UICC stage II and 33 (97%) patients were UICC stage III. Grade 3 acute toxicities occurred in 5 patients (15%). Patients with acute grade 1 cystitis (n = 9) had significantly higher D\(_{mean}\) values for bladder (29.4 Gy vs. 25.2 Gy, p < 0.01) compared to patients without bladder toxicities. Acute diarrhea was associated with small bowel volume (grade 2: 870.1 ccm vs. grade 0–1: 647.3 ccm; p < 0.01) and with the irradiated volumes V5 to V50. Using VMAT planning, we could reduce mean doses and irradiated volumes for all OAR: D\(_{mean}\) bladder (21.9 Gy vs. 26.3 Gy, p < 0.01), small bowel volumes V5–V45 (p < 0.01), D\(_{mean}\) anal sphincter (34.6 Gy vs. 35.6 Gy, p < 0.01) and D\(_{mean}\) femoral heads (right 11.4 Gy vs. 25.9 Gy, left 12.5 Gy vs. 26.6 Gy, p < 0.01). Acute small bowel and bladder toxicities were dose and volume dependent. Dose and volume sparing for all OAR could be achieved through VMAT planning and might result in less acute toxicities. KW - radiotherapy KW - rectal cancer Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-301255 VL - 12 ER - TY - JOUR A1 - Bliziotis, Nikolaos G. A1 - Kluijtmans, Leo A. J. A1 - Tinnevelt, Gerjen H. A1 - Reel, Parminder A1 - Reel, Smarti A1 - Langton, Katharina A1 - Robledo, Mercedes A1 - Pamporaki, Christina A1 - Pecori, Alessio A1 - Van Kralingen, Josie A1 - Tetti, Martina A1 - Engelke, Udo F. H. A1 - Erlic, Zoran A1 - Engel, Jasper A1 - Deutschbein, Timo A1 - Nölting, Svenja A1 - Prejbisz, Aleksander A1 - Richter, Susan A1 - Adamski, Jerzy A1 - Januszewicz, Andrzej A1 - Ceccato, Filippo A1 - Scaroni, Carla A1 - Dennedy, Michael C. A1 - Williams, Tracy A. A1 - Lenzini, Livia A1 - Gimenez-Roqueplo, Anne-Paule A1 - Davies, Eleanor A1 - Fassnacht, Martin A1 - Remde, Hanna A1 - Eisenhofer, Graeme A1 - Beuschlein, Felix A1 - Kroiss, Matthias A1 - Jefferson, Emily A1 - Zennaro, Maria-Christina A1 - Wevers, Ron A. A1 - Jansen, Jeroen J. A1 - Deinum, Jaap A1 - Timmers, Henri J. L. M. T1 - Preanalytical pitfalls in untargeted plasma nuclear magnetic resonance metabolomics of endocrine hypertension JF - Metabolites N2 - 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. KW - confounders KW - metabolomics KW - multicenter KW - plasma NMR KW - preanalytical conditions Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-282930 SN - 2218-1989 VL - 12 IS - 8 ER -