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9 result(s) for "von der Grün, Maximilian"
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A Continuous, Semi-Automated Workflow: From 3D City Models with Geometric Optimization and CFD Simulations to Visualization of Wind in an Urban Environment
The concept and implementation of Smart Cities is an important approach to improve decision making as well as quality of life of the growing urban population. An essential part of this is the presentation of data from different sources within a digital city model. Wind flow at building scale has a strong impact on many health and energy issues in a city. For the analysis of urban wind, Computational Fluid Dynamics (CFD) has become an established tool, but requires specialist knowledge to prepare the geometric input during a time-consuming process. Results are available only as predefined selections of pictures or videos. In this article, a continuous, semi-automated workflow is presented, which ❶ speeds-up the preparation of CFD simulation models using a largely automated geometry optimization; and ❷ enables web-based interactive exploration of urban wind simulations to a large and diverse audience, including experts and layman. Results are evaluated based on a case study using a part of a district in Stuttgart in terms of: ➀ time saving of the CFD model preparation workflow (85% faster than the manual method), ➁ response time measurements of different data formats within the Smart City platform (3D Tiles loaded 30% faster than geoJSON using the same data representations) and ➂ protocols (3DPS provided much higher flexibility than static and 3D container API), as well as ➃ subjective user experience analysis of various visualization schemes of urban wind. Time saving for the model optimization may, however, vary depending on the data quality and the extent of the study area.
Numerical Study of the Impact of Urban Terrain on the Loads and Performance of a Small Vertical Axis Wind Turbine
In the present study, the performance of a small vertical axis wind turbine (VAWT) is investigated in realistic urban terrain, in presence of large buildings, hill and forested area. Normally, accelerated wind can be observed on the roof-top of the high-rise buildings. Thereby, different factors such as the orography, vegetation and presence of the buildings at the site etc. influence the inflow conditions strongly and subsequently the performance and loads of wind turbines. Due to the continuously varying inflow direction, inclination and highly turbulent nature of the wind, a detailed analysis of the flow field around the building is required. A two-stages approach is preferred to reduce complexity of the problem. In the first part, the inflow conditions are investigated in the large domain by means of CFD and in the second part, performance and loads of the roof-top mounted small VAWT are investigated.
MRI-based radiomics for predicting histology in malignant salivary gland tumors: methodology and “proof of principle”
Defining the exact histological features of salivary gland malignancies before treatment remains an unsolved problem that compromises the ability to tailor further therapeutic steps individually. Radiomics, a new methodology to extract quantitative information from medical images, could contribute to characterizing the individual cancer phenotype already before treatment in a fast and non-invasive way. Consequently, the standardization and implementation of radiomic analysis in the clinical routine work to predict histology of salivary gland cancer (SGC) could also provide improvements in clinical decision-making. In this study, we aimed to investigate the potential of radiomic features as imaging biomarker to distinguish between high grade and low-grade salivary gland malignancies. We have also investigated the effect of image and feature level harmonization on the performance of radiomic models. For this study, our dual center cohort consisted of 126 patients, with histologically proven SGC, who underwent curative-intent treatment in two tertiary oncology centers. We extracted and analyzed the radiomics features of 120 pre-therapeutic MRI images with gadolinium (T1 sequences), and correlated those with the definitive post-operative histology. In our study the best radiomic model achieved average AUC of 0.66 and balanced accuracy of 0.63. According to the results, there is significant difference between the performance of models based on MRI intensity normalized images + harmonized features and other models ( p value < 0.05) which indicates that in case of dealing with heterogeneous dataset, applying the harmonization methods is beneficial. Among radiomic features minimum intensity from first order, and gray level-variance from texture category were frequently selected during multivariate analysis which indicate the potential of these features as being used as imaging biomarker. The present bicentric study presents for the first time the feasibility of implementing MR-based, handcrafted radiomics, based on T1 contrast-enhanced sequences and the ComBat harmonization method in an effort to predict the formal grading of salivary gland carcinoma with satisfactory performance.
Head and neck tumor organoid biobank for modelling individual responses to radiation therapy according to the TP53/HPV status
Background Head and neck cancers (HNC) represent an extremely heterogeneous group of diseases with a poorly predictable therapy outcome. Patient-derived tumor organoids (PDTO) offer enormous potential for individualized therapy testing and a better mechanistic understanding of the main HNC drivers. Methods Here, we have established a comprehensive molecularly and functionally characterized head and neck organoid biobank (HNOB) recapitulating the clinically relevant subtypes of TP53 mutant and human papillomavirus type 16 (HPV 16) infection-driven HNC. Organoids were exposed to radiotherapy, and responses were correlated with clinical data. Genetically engineered normal and tumor organoids were used for testing the direct functional consequences of TP53-loss and HPV infection. Results The HNOB consisting of 18 organoid models, including 15 tumor models, was generated. We identified subtype-associated transcriptomic signatures and pathological features, including sensitivity to TP53 stabilization by the MDM2 inhibitor Nutlin-3. Furthermore, we describe an in vitro radio response assay revealing phenotypic heterogeneity linked to the individual patient’s treatment outcome, including relapse probability. Using genetically engineered organoids, the possibility of co-existence of both cancer drivers was confirmed. TP53 loss, as well as HPV, increased growth in normal and tumor organoids. TP53 loss-of-function alone was insufficient to promote radiation resistance, whereas HPV 16 oncogenes E6/E7 mediated radiosensitivity via induction of cell cycle arrest. Conclusion Our results highlight the translational value of the head and neck organoid models not only for patient stratification but also for mechanistic validation of therapy responsiveness of specific cancer drivers.
Risk stratification by anamnesis increases SARS-CoV-2 test efficiency in cancer patients
PurposeTo evaluate the impact of testing asymptomatic cancer patients, we analyzed all tests for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) before and during radiotherapy at a tertiary cancer center throughout the second wave of the pandemic in Germany.MethodsResults of all real-time polymerase chain reaction (RT-PCR) tests for SARS-CoV‑2 performed at our radio-oncology department between 13 October 2020 and 11 March 2021 were included. Clinical data and anamnestic information at the time of testing were documented and examined for (i) the presence of COVID-19-related symptoms and (ii) virus-related anamnesis (high-risk [prior positive test or contact to a positive tested person within the last 14 days] or low-risk [inconspicuous anamnesis within the last 14 days]).ResultsA total of 1056 SARS-CoV‑2 tests in 543 patients were analyzed. Of those, 1015 tests were performed in asymptomatic patients and 41 tests in patients with COVID-19-associated symptoms. Two of 940 (0.2%) tests in asymptomatic patients with low-risk anamnesis and three of 75 (4.0%) tests in asymptomatic patients with high-risk anamnesis showed a positive result. For symptomatic patients, SARS-CoV‑2 was detected in three of 36 (8.3%) low-risk and three of five (60.0%) high-risk tests.ConclusionTo the best of our knowledge, this is the first study evaluating the correlation between individual risk factors and positivity rates of SARS-CoV‑2 tests in cancer patients. The data demonstrate that clinical and anamnestic assessment is a simple and effective measure to distinctly increase SARS-CoV‑2 test efficiency. This might enable cancer centers to adjust test strategies in asymptomatic patients, especially when test resources are scarce.
Single Center Characterization of a Cohort of Salivary Gland Carcinomas
Salivary gland cancer (SGC) is a rare cancer that can present a diagnostic challenge to pathologists, with emerging, but still limited options for the treatment of recurrent/metastatic disease. We aimed to characterize the cohort of salivary gland cancers in our institute and generate a tissue microarray (TMA) with clinical data available for immunohistochemical analysis. We extracted the cases of salivary gland cancers in our institute and generated a TMA with 72 patients between 2002 and 2017 with sufficient paraffin block material. Follow-up data were present for all cases. The TMA was stained with three p53 antibodies as well as MSH2, MSH6, PMS2 and MLH1 antibodies. Additionally, we applied fragment analysis based on the Bethesda panel, and the IdyllaTM MSI test to cases with expression loss of any of the mismatch repair proteins (MMR-P) according to our immunohistochemistry (IHC). The investigated cohort shows that pT and pN stage are the only factors independently associated with survival, according to our multivariate analysis (p = 0.037 and p = 0.014). In univariate analysis, risk factors identified in our cohort were also age (p = 0.015), (lympho-) vascular invasion (p = 0.002 and p = 0.003) and risk stratification (p = 0.037). The p53 protein investigated by three antibodies showed no statistically significant association with survival or other tumor characteristics in the investigated cohort. According to MMR-P IHC, six cases of SGC showed an aberrant IHC phenotype. Additional IdyllaTM MSI test and fragment length analysis failed to confirm microsatellite instability. The pT and pN stage are the most important factors for survival in our cohort. In our cohort, antibodies directed against the protein p53 did not contribute to clinical decision-making and were not correlated with any known clinical characteristics. MSI appears to be insignificant in SGCs. Larger cohorts are needed for verification.
Implementation of Double Immune Checkpoint Blockade Increases Response Rate to Induction Chemotherapy in Head and Neck Cancer
To determine whether a single dose of double immune checkpoint blockade (induction chemoimmunotherapy (ICIT)) adds benefit to induction single-cycle platinum doublet (induction chemotherapy (IC)) in locally advanced head and neck squamous cell carcinoma (HNSCC), patients treated with cisplatin 30 mg/m2 d1-3 and docetaxel 75 mg/m2 d1 combined with durvalumab 1500 mg fixed dose d5 and tremelimumab 75 mg fixed dose d5 (ICIT) within the CheckRad-CD8 trial were compared with a retrospective cohort receiving the same chemotherapy (IC) without immunotherapy. The endpoint of this analysis was the complete response rate (CR). A total of 53 patients were treated with ICIT and 104 patients with IC only. CR rates were 60.3% for ICIT and 40.3% for IC (p = 0.018). In the total population (n = 157), the most important predictor to achieve a CR was treatment type (OR: 2.21 for ICIT vs. IC; p = 0.038, multivariate analysis). The most diverse effects in CR rates between ICIT and IC were observed in younger (age ≤ 60) patients with HPV-positive OPSCCs (82% vs. 33%, p = 0.176), while there was no difference in older patients without HPV-positive OPSCCs (53% vs. 48%). The analysis provides initial evidence that ICIT could result in higher CR rates than IC. Young patients with HPV-positive OPSCCs may have the greatest benefit from additional immune checkpoint inhibitors.
Reduction of Elective Radiotherapy Treatment Volume in Definitive Treatment of Locally Advanced Head and Neck Cancer—Comparison of a Prospective Trial with a Revised Simulated Contouring Approach
Definitive radiochemotherapy of locally advanced head and neck squamous cell cancer (HNSCC) achieves high locoregional tumor control rates; but is frequently associated with long-term toxicity. A future direction could be a de-escalation strategy focusing on treated volume rather than radiotherapy dose. This analysis evaluates radiotherapy dose and volume parameters of patients treated with a standard contouring approach in a clinical trial context compared with a revised volume-reduced contouring approach. In this case, 30 consecutive patients from the CheckRad-CD8 trial treated at a single study center were included in this analysis. Treatment toxicity and quality of life were assessed at the end of radiotherapy. Standard treatment plans (ST) following state of the art contouring guidelines that were used for patient treatment and volume reduced treatment plans (VRT) according to a revised simulated approach were calculated for each patient. Planning target volumes (PTV) and mean doses to 38 organs-at-risk structures were compared. At the end of radiotherapy patients reported high rates of mucositis; dysphagia and xerostomia. In addition; patient reported quality of life as assessed by the EORTC QLQ-HN35 questionnaire deteriorated. Comparing the two contouring approaches; the elective PTV_56 Gy and the high risk PTV_63 Gy (shrinking field) were significantly smaller in the VRT group. Significant reduction of mean dose to structures of the oral cavity; the larynx as well as part of the swallowing muscles and the submandibular glands was achieved in the simulated VRT-plan. Treatment de-intensification by reduction of the irradiated volume could potentially reduce treatment volume and mean doses to organs at risk. The proposed contouring approach should be studied further in the context of a clinical trial.