@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{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{HardcastleTomeCannonetal.2012, author = {Hardcastle, Nicholas and Tom{\´e}, Wolfgang A. and Cannon, Donald M. and Brouwer, Charlotte L. and Wittendorp, Paul W. H. and Dogan, Nesrin and Guckenberger, Matthias and Allaire, St{\´e}phane and Mallya, Yogish and Kumar, Prashant and Oechsner, Markus and Richter, Anne and Song, Shiyu and Myers, Michael and Polat, B{\"u}lent and Bzdusek, Karl}, title = {A multi-institution evaluation of deformable image registration algorithms for automatic organ delineation in adaptive head and neck radiotherapy}, series = {Radiation Oncology}, volume = {7}, journal = {Radiation Oncology}, number = {90}, doi = {10.1186/1748-717X-7-90}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-134756}, year = {2012}, abstract = {Background: Adaptive Radiotherapy aims to identify anatomical deviations during a radiotherapy course and modify the treatment plan to maintain treatment objectives. This requires regions of interest (ROIs) to be defined using the most recent imaging data. This study investigates the clinical utility of using deformable image registration (DIR) to automatically propagate ROIs. Methods: Target (GTV) and organ-at-risk (OAR) ROIs were non-rigidly propagated from a planning CT scan to a per-treatment CT scan for 22 patients. Propagated ROIs were quantitatively compared with expert physician-drawn ROIs on the per-treatment scan using Dice scores and mean slicewise Hausdorff distances, and center of mass distances for GTVs. The propagated ROIs were qualitatively examined by experts and scored based on their clinical utility. Results: Good agreement between the DIR-propagated ROIs and expert-drawn ROIs was observed based on the metrics used. 94\% of all ROIs generated using DIR were scored as being clinically useful, requiring minimal or no edits. However, 27\% (12/44) of the GTVs required major edits. Conclusion: DIR was successfully used on 22 patients to propagate target and OAR structures for ART with good anatomical agreement for OARs. It is recommended that propagated target structures be thoroughly reviewed by the treating physician.}, 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} } @article{MantelMuellerKleineetal.2021, author = {Mantel, Frederick and M{\"u}ller, Elena and Kleine, Philip and Zimmermann, Marcus and Exner, Florian and Richter, Anne and Weick, Stefan and Str{\"o}hle, Serge and Polat, B{\"u}lent and H{\"o}cht, Stefan and Flentje, Michael}, title = {Chemoradiotherapy by intensity-modulated radiation therapy with simultaneous integrated boost in locally advanced or oligometastatic non-small-cell lung cancer-a two center experience}, series = {Strahlentherapie und Onkologie}, volume = {197}, journal = {Strahlentherapie und Onkologie}, number = {5}, issn = {1439-099X}, doi = {10.1007/s00066-021-01756-7}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-264821}, pages = {405-415}, year = {2021}, abstract = {Purpose Integrating moderate hypofractionation to the macroscopic tumor with elective nodal irradiation while sparing the organs at risk (OAR) in chemoradiotherapy of locally advanced non-small-cell lung cancer. Methods From 2010-2018, treatment, patient and tumor characteristics of 138 patients from two radiation therapy centers were assessed. Chemoradiotherapy by intensity-modulated radiation therapy (IMRT) with a simultaneous integrated boost (SIB) to the primary tumor and macroscopic lymph node metastases was used. Results A total of 124 (90\%) patients received concurrent chemotherapy. 106 (76\%) patients had UICC (Union for International Cancer Control) stage ≥IIIB and 21 (15\%) patients had an oligometastatic disease (UICC stage IV). Median SIB and elective total dose was 61.6 and 50.4 Gy in 28 fractions, respectively. Furthermore, 64 patients (46\%) had an additional sequential boost to the primary tumor after the SIB-IMRT main series: median 6.6 Gy in median 3 fractions. The median cumulative mean lung dose was 15.6 Gy (range 6.2-29.5 Gy). Median follow-up and radiological follow-up for all patients was 18.0 months (range 0.6-86.9) and 16.0 months (range 0.2-86.9), respectively. Actuarial local control rates at 1, 2 and 3 years were 80.4, 68.4 and 57.8\%. Median overall survival and progression-free survival was 30.0 months (95\% confidence interval [CI] 23.5-36.4) and 12.1 months (95\% CI 8.2-16.0), respectively. Treatment-related toxicity was moderate. Radiation-induced pneumonitis grade 2 and grade 3 occurred in 13 (9.8\%) and 3 (2.3\%) patients. Conclusions Chemoradiotherapy using SIB-IMRT showed promising local tumor control rates and acceptable toxicity in patients with locally advanced and in part oligometastatic lung cancer. The SIB concept, resulting in a relatively low mean lung dose, was associated with low numbers of clinically relevant pneumonitis. The overall survival appears promising in the presence of a majority of patients with UICC stage ≥IIIB disease.}, 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{RichterWegenerBreueretal.2021, author = {Richter, Anne and Wegener, Sonja and Breuer, Kathrin and Razinskas, Gary and Weick, Stefan and Exner, Florian and Bratengeier, Klaus and Flentje, Michael and Sauer, Otto and Polat, B{\"u}lent}, title = {Comparison of sliding window and field-in-field techniques for tangential whole breast irradiation using the Halcyon and Synergy Agility systems}, series = {Radiation Oncology}, volume = {16}, journal = {Radiation Oncology}, doi = {10.1186/s13014-021-01942-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265704}, year = {2021}, abstract = {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.}, 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{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} }