Corrigendum: Low Dose Radiation Therapy Induces Long-Lasting Reduction of Pain and Immune Modulations in the Peripheral Blood - Interim Analysis of the IMMO-LDRT01 Trial(Front. Immunol., (2021), 12, (740742), 10.3389/fimmu.2021.740742) - Donaubauer, Anna-Jasmina; Becker, Ina; Weissmann, Thomas; Fröhlich, Birgitta; Munoz, Luis Enrique; Gryc, Thomas; Denzler, Manuel; Ott, Oliver; Fietkau, Rainer; Gaipl, Udo; Frey, Benjamin (Frontiers in Immunology, 2022)
In the original article, there was an error. The mistake is found in the sentence “While the total number of leukocytes remained unchanged in the peripheral blood, LDRT induced a slight reduction of eosinophils, basophils and plasmacytoid dendritic cells and an increase of B cells.” in the abstract of the article.
CRIS-Team Scopus Importer:2022-03-04
Keywords: chronic degenerative and inflammatory diseases; immune status; immunophenotyping; low dose radiation therapy (LDRT); subjective pain level; x-rays

Creation of an Electro-magnetic Heat Simulation for Planning Hyperthermia Treatments for Mice - Kahlert, B.; Bert, Christoph; Rückert, Michael; Hensel, Bernhard; Root, Konstantin; Vossiek, Martin; Fietkau, Rainer; Gaipl, Udo; Frey, Benjamin (STRAHLENTHERAPIE UND ONKOLOGIE, 2022)
CRIS-Team WoS Importer:2022-06-03

CRISPR-Cas9 Screen Identifies DYRK1A as a Target for Radiotherapy Sensitization in Pancreatic Cancer - Lan, Bin; Zeng, Siyuan; Zhang, Shuman; Ren, Xiaofan; Xing, Yuming; Kutschick, Isabella; Pfeffer, Sina; Frey, Benjamin; Britzen-Laurent, Nathalie; Grützmann, Robert; Cordes, Nils; Pilarsky, Christian (Cancers, 2022)
Although radiation therapy has recently made great advances in cancer treatment, the majority of patients diagnosed with pancreatic cancer (PC) cannot achieve satisfactory outcomes due to intrinsic and acquired radioresistance. Identifying the molecular mechanisms that impair the efficacy of radiotherapy and targeting these pathways are essential to improve the radiation response of PC patients. Our goal is to identify sensitive targets for pancreatic cancer radiotherapy (RT) using the kinome-wide CRISPR-Cas9 loss-of-function screen and enhance the therapeutic effect through the development and application of targeted inhibitors combined with radiotherapy. We transduced pancreatic cancer cells with a protein kinase library; 2D and 3D library cells were irradiated daily with a single dose of up to 2 Gy for 4 weeks for a total of 40 Gy using an X-ray generator. Sufficient DNA was collected for next-generation deep sequencing to identify candidate genes. In this study, we identified several cell cycle checkpoint kinases and DNA damage related kinases in 2D-and 3D-cultivated cells, including DYRK1A, whose loss of function sensitizes cells to radiotherapy. Additionally, we demonstrated that the harmine-targeted suppression of DYRK1A used in conjunction with radiotherapy increases DNA double-strand breaks (DSBs) and impairs homologous repair (HR), resulting in more cancer cell death. Our results support the use of CRISPR-Cas9 screening to identify new therapeutic targets, develop radiosensitizers, and provide novel strategies for overcoming the tolerance of pancreatic cancer to radiotherapy.
CRIS-Team Scopus Importer:2022-01-14
Keywords: CRISPR-Cas9; DNA damage repair; DNA double-strand break; DYRK1A; Harmine; Pancreatic cancer; Radioresistance; Radiotherapy

Critical role of spatial interaction between CD8? and Foxp3? cells in human gastric cancer: the distance matters - Feichtenbeiner, Anita; Haas, Matthias; Büttner, Maike; Grabenbauer, Gerhard; Fietkau, Rainer; Distel, Luitpold (Cancer Immunology Immunotherapy, 2014)
In various cancer types, an abundance of FoxP3(+) regulatory T cells (Treg) has been associated with an unfavorable outcome. Yet, the role of Treg on cancer immunity has been shown to be complex. In single cell marker technique, other tumor-infiltrating lymphocytes (TILs) such as cytotoxic CD8(+) T cells (CTL) also influenced prognosis. This study for the first time investigates the concurrent spatial distribution pattern of CD8(+) and FoxP3(+) TILs and their prognostic impact in human gastric cancer.Tumor tissue microarrays of 50 patients with surgically treated adenocarcinoma of the cardia were studied. An immunohistochemical double staining of CD8(+) and FoxP3(+) TILs was performed. Cell counts and cell-to-cell distances in tumor epithelium and stroma were evaluated with image-processing software. Metastasis-free survival, no-evidence-of-disease survival, and overall survival were investigated (mean follow-up time 6.9 years).High intraepithelial infiltration of CD8(+) and FoxP3(+) TIL was associated with the improved 10-year metastasis-free survival (83 vs. 54%, p = 0.04 and 85 vs. 59%, p = 0.09, respectively). Considering cell-to-cell distance and comparing patients with functional (30-110 ?m) versus nonfunctional distances of CD8(+) and FoxP3(+) TILs, 10-year survival rates differed between 89 and 55% (p = 0.009), respectively.Prognostic influence of tumor-infiltrating immune cells in gastric cancer critically depends on their cell-to-cell distance. FoxP3(+) TILs must be located within a distance between 30 and 110 ?m of CD8(+) T cells to positively impact on prognosis.
EVALuna2:18176

CtDNA release mechanisms in a therapeutic Ewing Sarcoma mouse model - Eiblwieser, Johanna; Krumbholz, Manuela; Semper, S.; Frey, Benjamin; Nagel, L.; Bäuerle, Tobias; Metzler, Markus (KLINISCHE PADIATRIE, 2022)
CRIS-Team WoS Importer:2022-07-08

Current controversies in radiotherapy for breast cancer - Krug, David; Baumann, Rene; Budach, Wilfried; Dunst, Juergen; Feyer, Petra; Fietkau, Rainer; Haase, Wulf; Harms, Wolfgang; Piroth, Marc D.; Sautter-Bihl, Marie-Luise; Sedlmayer, Felix; Souchon, Rainer; et al. (Radiation Oncology, 2017)
Multimodal treatment approaches have substantially improved the outcome of breast cancer patients in the last decades. Radiotherapy is an integral component of multimodal treatment concepts used in curative and palliative intention in numerous clinical situations from precursor lesions such as ductal carcinoma in situ (DCIS) to advanced breast cancer. This review addresses current controversial topics in radiotherapy with special consideration of DCIS, accelerated partial breast irradiation (APBI) and regional nodal irradiation (RNI) and provides an update on the clinical practice guidelines of the Breast Cancer Expert Panel of the German Society of Radiation Oncology (DEGRO).
EVALuna2:32913

Cytotoxic and immunogenic Potential of Iron (II) Clathrochelates and Irradiation on Lung Cancer Cell Lines - Becker, Ina; Denzler, M.; Heim, Lisanne; Klemt, Insa; Voloshin, Y. Z.; Selin, R.; Mokhir, Andriy; Fietkau, Rainer; Gaipl, Udo; Frey, Benjamin (STRAHLENTHERAPIE UND ONKOLOGIE, 2021)
CRIS-Team WoS Importer:2021-07-16

Cytotoxic and immunosuppressive inflammatory cells predict regression and prognosis following neoadjuvant radiochemotherapy of oesophageal adenocarcinoma - Göbel, Holger H.; Büttner-Herold, Maike; Fuhrich, Nicole; Aigner, Thomas; Grabenbauer, Gerhard G.; Distel, Luitpold (Radiotherapy and Oncology, 2020)
Background and purpose: Tumour infiltrating lymphocytes (TIL) and tumour associated macrophages (TAM) play a key role in anticancer immunosurveillance. We studied their influence on response to neoadjuvant radiochemotherapy (RCT) and prognosis in patients with oesophageal adenocarcinoma (OAC). Materials and methods: Between 10/2004 and 06/2018, pre-RCT biopsy-specimens were available from 76 patients with locally advanced, non-metastatic OAC scheduled for trimodality therapy. We evaluated intra- and peritumoural expression of FoxP3+-, CD8+-TIL and CD68+-, CD163+-TAM, contemplating cell density, cell ratios and cell-to-cell distances to determine a possible influence on tumour regression grade (TRG) and survival. Median follow-up time for all patients was 18 months (IQR 9–43), and 54 months (25–97) for surviving patients. Data were analysed using risk analysis, logrank test and Cox regression. Results: Poor tumour regression was detected for cN+ (RR 0.77 [95% CI 0.66–0.90], p = 0.001), low intratumoural FoxP3+/CD8+ ratio (RR 0.75 [0.60–0.96], p = 0.020), high peritumoural CD163+/CD68+ ratio (RR 0.77 [0.60–0.99], p = 0.045) and high intratumoural TAM density (RD −0.44 [−0.82 to −0.06], p = 0.023). Apart from poor resection quality and TRG, pretherapeutic high peritumoural CD8+ infiltration (HR 2.36 [1.21–4.61], p = 0.012) and short intratumoural FoxP3+ to CD8+ cell-to-cell distances in middle ranged CD8+ density (HR 2.55 [1.00–6.52], p = 0.050) were significant unfavourable prognostic factors in multivariate analysis. Conclusions: Immunologic parameters, such as CD8+-, FoxP3+-TIL and CD68+-, CD163+-TAM, were identified to be of independent predictive and prognostic value in patients with OAC. Further and independent validation of these biomarkers by a large size dataset may urgently be contemplated.
CRIS-Team Scopus Importer:2020-03-20
Keywords: CD163+; CD68+; CD8+; FoxP3+; Oesophageal adenocarcinoma; Radiochemotherapy

Cytotoxic effect of Efavirenz in BxPC-3 pancreatic cancer cells is based on oxidative stress and is synergistic with ionizing radiation - Hecht, Markus; Harrer, Thomas; Koeber, Verena; Sarpong, Eric Opoku; Moser, Fabian; Fiebig, Nora; Schwegler, Manuela; Stürzl, Michael; Fietkau, Rainer; Distel, Luitpold (Oncology Letters, 2018)
The non-nucleoside reverse transcriptase inhibitor (NNRTI) Efavirenz is frequently used in human immunodeficiency virus treatment, but also efficient against cancer in mouse models. Its radiosensitizing effect makes it a promising drug for combination with radiotherapy. The efficacy of Efavirenz combined with irradiation was assessed with immunostaining of DNA-damage markers and colony formation assays in BxPC-3 pancreatic cancer cells. Gene expression and protein phosphorylation of the Efavirenz-sensitive BxPC-3 cells was compared to the resistant primary fibroblasts SBL-5. Oxidative stress, mitochondrial damage and cell death were studied with live-cell microscopy and flow cytometry. Combined Efavirenz and radiation significantly increased the number of γH2AX and phospho-ataxia telangiectasia mutated foci. Efavirenz and ionizing radiation had a synergistic effect using the clonogenic survival assay. Efavirenz selectively induced cell death in the BxPC-3 cells. The differing gene expression of cell cycle and apoptotic regulator genes in both cell cultures after Efavirenz treatment match with this selective effect against cancer cells. In the phosphoprotein array, an early phosphorylation of extracellular signal-related kinase 1/2 and p38 mitogen-activated protein kinase was notably detected in the cancer cells. The phosphorylation of AKT decreased in the cancer cells whereas it increased in the fibroblasts. Oxidative stress and mitochondrial membrane depolarization appeared in the cancer cells immediately after Efavirenz treatment, but not in the fibroblasts. Efavirenz has an anti-cancer effect against pancreatic cancer mainly by the induction of oxidative stress. The antitumor potential of Efavirenz and radiotherapy are additive.
EVALuna2:36443

DAPK-HSF1 interaction as a positive-feedback mechanism stimulating TNF-induced apoptosis in colorectal cancer cells - Benderska, Natalya; Ivanovska, Jelena; Rau, Tilman; Schulze-Luehrmann, Jan; Mohan, Suma; Chakilam, Saritha; Gandesiri, Muktheshwar; Ziesche, Elisabeth; Fischer, Thomas; Söder, Stephan; Agaimy, Abbas; Distel, Luitpold; et al. (Journal of Cell Science, 2014)
Death-associated protein kinase (DAPK) is a serine-threonine kinase with tumor suppressor function. Previously, we demonstrated that tumor necrosis factor (TNF) induced DAPK-mediated apoptosis in colorectal cancer. However, the protein-protein interaction network associated with TNF-DAPK signaling still remains unclear. We identified HSF1 as a new DAPK phosphorylation target in response to low concentrations of TNF and verified a physical interaction between DAPK and HSF1 both in vitro and in vivo. We show that HSF1 binds to the DAPK promoter. Transient overexpression of HSF1 protein led to an increase in DAPK mRNA level and consequently to an increase in the amount of apoptosis. By contrast, treatment with a DAPK-specific inhibitor as well as DAPK knockdown abolished the phosphorylation of HSF1 at Ser230 (pHSF1(Ser230)). Furthermore, translational studies demonstrated a positive correlation between DAPK and pHSF1(Ser230) protein expression in human colorectal carcinoma tissues. Taken together, our data define a novel link between DAPK and HSF1 and highlight a positive-feedback loop in DAPK regulation under mild inflammatory stress conditions in colorectal tumors. For the first time, we show that under TNF the pro-survival HSF1 protein can be redirected to a pro-apoptotic program.
EVALuna2:6637

Decoupling Respiratory and Angular Variation in Rotational X-ray Scans Using a Prior Bilinear Model - Geimer, Tobias; Keall, Paul; Breininger, Katharina; Caillet, Vincent; Dunbar, Michelle; Bert, Christoph; Maier, Andreas (Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics), 2019)
Data-driven respiratory signal extraction from rotational X-ray scans is a challenge as angular effects overlap with respiration-induced change in the scene. In this paper, we use the linearity of the X-ray transform to propose a bilinear model based on a prior 4D scan to separate angular and respiratory variation. The bilinear estimation process is supported by a B-spline interpolation using prior knowledge about the trajectory angle. Consequently, extraction of respiratory features simplifies to a linear problem. Though the need for a prior 4D CT seems steep, our proposed use-case of driving a respiratory motion model in radiation therapy usually meets this requirement. We evaluate on DRRs of 5 patient 4D CTs in a leave-one-phase-out manner and achieve a mean estimation error of 3.01% in the gray values for unseen viewing angles. We further demonstrate suitability of the extracted weights to drive a motion model for treatments with a continuously rotating gantry.
CRIS-Team Scopus Importer:2019-06-21
Keywords: Bilinear model; Feature extraction; Motion model; Respiratory signal; X-ray projection

Decrease of Markers Related to Bone Erosion in Serum of Patients with Musculoskeletal Disorders after Serial Low-Dose Radon Spa Therapy - Cucu, Aljona; Shreder, Kateryna; Kraft, Daniela; Ruhle, Paul Friedrich; Klein, Gerhart; Thiel, Gerhard; Frey, Benjamin; Gaipl, Udo; Fournier, Claudia (Frontiers in Immunology, 2017)
Musculoskeletal disorders (MSDs) are the most frequent cause of disability in Europe. Reduced mobility and quality of life of the patients are often associated with pain due to chronic inflammation. The inflammatory process, accompanied by a destruction of the cartilage and bone tissue, is discussed as a result of (A) the infiltration of immune cells into the joints, (B) an altered homeostasis of the joint cavity (synovium) with a critical role of bone remodeling cells, and (C) release of inflammatory factors including adipokines in the arthritic joint. In addition to the classical medication, low-dose radiation therapy using photons or radon spa treatments has shown to reduce pain and improve the mobility of the patients. However, the cellular and molecular mechanisms of anti-inflammatory effects of radon are yet poorly understood. We analyzed blood and serum samples from 32 patients, suffering from MSDs, who had been treated in the radon spa in Bad Steben (Germany). Before and after therapy, we measured the levels of markers related to bone metabolism (collagen fragments type-1, cartilage oligomeric matrix protein, receptor activator of NFκB ligand, and osteoprotegerin) in the serum of patients. In addition, adipokines related to inflammation (visfatin, leptin, resistin, and adiponectin) were analyzed. Some of these factors are known to correlate with disease activity. Since T cells play an important role in the progression of the disease, we further analyzed in blood samples the frequency of pro- and anti-inflammatory T cell subpopulations (CD4+IL17+T cells and CD4+FoxP3+regulatory T cells). Overall, we found a decrease of collagen fragments (CTX-I), indicating decreased bone resorption, presumably by osteoclasts, in the serum of MSD patients. We also observed reduced levels of visfatin and a consistent trend toward an increase of regulatory T cells in the peripheral blood, both indicating attenuation of inflammation. However, key proteins of bone metabolism were unchanged on a systemic level, suggesting that these factors act locally after radon spa therapy of patients with MSDs.
EVALuna2:32927

Deep Learning and Registration-Based Mapping for Analyzing the Distribution of Nodal Metastases in Head and Neck Cancer Cohorts: Informing Optimal Radiotherapy Target Volume Design - Weissmann, Thomas; Mansoorian, Sina; May, Matthias; Lettmaier, Sebastian; Höfler, Daniel; Deloch, Lisa; Speer, Stefan; Balk, Matthias; Frey, Benjamin; Gaipl, Udo; Bert, Christoph; Distel, Luitpold; et al. (Cancers, 2023)
We introduce a deep-learning- and a registration-based method for automatically analyzing the spatial distribution of nodal metastases (LNs) in head and neck (H/N) cancer cohorts to inform radiotherapy (RT) target volume design. The two methods are evaluated in a cohort of 193 H/N patients/planning CTs with a total of 449 LNs. In the deep learning method, a previously developed nnU-Net 3D/2D ensemble model is used to autosegment 20 H/N levels, with each LN subsequently being algorithmically assigned to the closest-level autosegmentation. In the nonrigid-registration-based mapping method, LNs are mapped into a calculated template CT representing the cohort-average patient anatomy, and kernel density estimation is employed to estimate the underlying average 3D-LN probability distribution allowing for analysis and visualization without prespecified level definitions. Multireader assessment by three radio-oncologists with majority voting was used to evaluate the deep learning method and obtain the ground-truth distribution. For the mapping technique, the proportion of LNs predicted by the 3D probability distribution for each level was calculated and compared to the deep learning and ground-truth distributions. As determined by a multireader review with majority voting, the deep learning method correctly categorized all 449 LNs to their respective levels. Level 2 showed the highest LN involvement (59.0%). The level involvement predicted by the mapping technique was consistent with the ground-truth distribution (p for difference 0.915). Application of the proposed methods to multicenter cohorts with selected H/N tumor subtypes for informing optimal RT target volume design is promising.<br
Keywords: deep learning; artificial intelligence; nodal metastasis; head and neck cancer; radiotherapy; target volume design; atlas; mapping; autosegmentation; lymph node level classification

Deep Learning-assisted delineation of brain metastases: a workflow focusing on AI-expert interaction - Putz, Florian; Szkitsak, Juliane; Grigo, Johanna; Masitho, Siti; Weissmann, Thomas; Frey, Benjamin; Gaipl, Udo; Fietkau, Rainer; Bert, Christoph; Huang, Yixing (Radiotherapy and Oncology, 2023)

Deep Learning-based Auto-contouring of Lymph Node Levels in Head and Neck Area - Weissmann, Thomas; Huang, Yixing; Sommer, Phillip; Roesch, Johannes; Mansoorian, Sina; Ayala, H.; Fischer, Stefan; Srinivasan, Aishwarya Lakshmi; Haderlein, Marlen; Hecht, Markus; Speer, Stefan; Schweizer, Claudia; et al. (STRAHLENTHERAPIE UND ONKOLOGIE, 2022)
CRIS-Team WoS Importer:2022-06-03

Deep Learning-based automatic longitudinal volumetric Analysis in Acoustic Neuroma - Putz, Florian; Chen, Hui-fen; Huang, Yixing; Weissmann, Thomas; Mansoorian, Sina; Schmidt, M.; Semrau, Sabine; Lettmaier, Sebastian; Bert, Christoph; Fietkau, Rainer (STRAHLENTHERAPIE UND ONKOLOGIE, 2022)
CRIS-Team WoS Importer:2022-06-03

Deep Learning based fully automated volumetric Progression Assessment in Patients with Brain Metastases after stereotactic Radiotherapy - Putz, Florian; Huang, Yixing; Weissmann, Thomas; Mansoorian, Sina; Sommer, P.; Fischer, S.; Srinivasan, A.; Frey, Benjamin; Gaipl, Udo; Schmidt, M.; Semrau, Sabine; Bert, Christoph; et al. (STRAHLENTHERAPIE UND ONKOLOGIE, 2022)
CRIS-Team WoS Importer:2022-06-03

Deep Learning based Prediction of Glioma Growth by using "Growing Neural Cellular Automata" - Huang, Yixing; Maier, Andreas; Sommer, Philipp; Fischer, Stefan; Srinivasan, Aishwarya Lakshmi; Fietkau, Rainer; Bert, Christoph; Putz, Florian (STRAHLENTHERAPIE UND ONKOLOGIE, 2022)
CRIS-Team WoS Importer:2022-06-03

Deep learning–based quantitative susceptibility mapping (QSM) in the presence of fat using synthetically generated multi-echo phase training data - Hanspach, Jannis; Bollmann, Steffen; Grigo, Johanna; Karius, Andre; Uder, Michael; Laun, Frederik Bernd (Magnetic Resonance in Medicine, 2022)
Purpose: To enable a fast and automatic deep learning–based QSM reconstruction of tissues with diverse chemical shifts, relevant to most regions outside the brain. Methods: A UNET was trained to reconstruct susceptibility maps using synthetically generated, unwrapped, multi-echo phase data as input. The RMS error with respect to synthetic validation data was computed. The method was tested on two in vivo knee and two pelvis data sets. Comparisons were made to a conventional fat–water separation pipeline by applying a commonly used graph-cut algorithm, both without and with an extended mask for background field removal (FWS-CONV-QSM and FWS-MASK-CONV-QSM, respectively). Several regions of interest were segmented and compared. Furthermore, the approach was tested on a prostate cancer patient receiving low-dose-rate brachytherapy, to detect and localize the seeds by MRI. Results: The RMS error was 0.292 ppm with FWS-CONV-QSM and 0.123 ppm for the UNET approach. Susceptibility maps were reconstructed much faster (< 10 s) and completely automatically (no background masking needed) by the UNET compared with the other applied techniques (5 min 51 s and 22 min 44 s for CONV-QSM and FWS-MASK-CONV-QSM, respectively. Background artifacts, fat–water swaps, and hypointense artifacts between I-125 seeds of a patient receiving low-dose brachytherapy in the prostate were largely reduced in the UNET approach. Conclusions: Deep learning–based QSM reconstruction, trained solely with synthetic data, is well-suited to rapidly reconstructing high-quality susceptibility maps in the presence of fat without needing masking for background field removal.
CRIS-Team Scopus Importer:2022-06-24
Keywords: deep learning; dipole inversion; fat–water separation; magnetic resonance imaging (MRI); prostate seed detection; quantitative susceptibility mapping (QSM)

Deep Learning basierte Vorhersage von Gliomwachstum mittels Growing Neural Cellular Automata - Huang, Yixing; Maier, Andreas; Sommer, Phillip; Fischer, Stefan; Srinivasan, Aishwarya Lakshmi; Fietkau, Rainer; Bert, Christoph; Putz, Florian (Strahlentherapie und Onkologie, 2022)
Keywords: deep learning; cellular automata; tumor growth

Deep learning for automatic head and neck lymph node level delineation provides expert-level accuracy - Weissmann, Thomas; Huang, Yixing; Fischer, Stefan; Roesch, Johannes; Mansoorian, Sina; Gaona, Horacio Ayala; Gostian, Antoniu-Oreste; Hecht, Markus; Lettmaier, Sebastian; Deloch, Lisa; Frey, Benjamin; Gaipl, Udo; et al. (Frontiers in Oncology, 2023)
Background: Deep learning-based head and neck lymph node level (HN_LNL) autodelineation is of high relevance to radiotherapy research and clinical treatment planning but still underinvestigated in academic literature. In particular, there is no publicly available open-source solution for large-scale autosegmentation of HN_LNL in the research setting. Methods: An expert-delineated cohort of 35 planning CTs was used for training of an nnU-net 3D-fullres/2D-ensemble model for autosegmentation of 20 different HN_LNL. A second cohort acquired at the same institution later in time served as the test set (n = 20). In a completely blinded evaluation, 3 clinical experts rated the quality of deep learning autosegmentations in a head-to-head comparison with expert-created contours. For a subgroup of 10 cases, intraobserver variability was compared to the average deep learning autosegmentation accuracy on the original and recontoured set of expert segmentations. A postprocessing step to adjust craniocaudal boundaries of level autosegmentations to the CT slice plane was introduced and the effect of autocontour consistency with CT slice plane orientation on geometric accuracy and expert rating was investigated. Results: Blinded expert ratings for deep learning segmentations and expert-created contours were not significantly different. Deep learning segmentations with slice plane adjustment were rated numerically higher (mean, 81.0 vs. 79.6, p = 0.185) and deep learning segmentations without slice plane adjustment were rated numerically lower (77.2 vs. 79.6, p = 0.167) than manually drawn contours. In a head-to-head comparison, deep learning segmentations with CT slice plane adjustment were rated significantly better than deep learning contours without slice plane adjustment (81.0 vs. 77.2, p = 0.004). Geometric accuracy of deep learning segmentations was not different from intraobserver variability (mean Dice per level, 0.76 vs. 0.77, p = 0.307). Clinical significance of contour consistency with CT slice plane orientation was not represented by geometric accuracy metrics (volumetric Dice, 0.78 vs. 0.78, p = 0.703). Conclusions: We show that a nnU-net 3D-fullres/2D-ensemble model can be used for highly accurate autodelineation of HN_LNL using only a limited training dataset that is ideally suited for large-scale standardized autodelineation of HN_LNL in the research setting. Geometric accuracy metrics are only an imperfect surrogate for blinded expert rating. <
Keywords: Deep learning; lymph node level; segmentation

Deep learning for brain metastasis detection and segmentation in longitudinal MRI data - Huang, Yixing; Bert, Christoph; Sommer, Philipp; Frey, Benjamin; Gaipl, Udo; Distel, Luitpold; Weissmann, Thomas; Uder, Michael; Schmidt, Manuel; Dörfler, Arnd; Maier, Andreas; Fietkau, Rainer; et al. (Medical Physics, 2022)
Keywords: Deep learning; brain metastasis; MRI; loss function; sensitivity specificity

Deep learning for perspective deformation correction in X-ray imaging - Huang, Yixing; Maier, Andreas; Fan, Fuxin; Kreher, Björn W.; Huang, Xiaolin; Fietkau, Rainer; Bert, Christoph; Putz, Florian (Radiotherapy and Oncology, 2023)
Keywords: Deep learning; perspective deformation; X-ray imaging

Defining metaniches in the oral cavity according to their microbial composition and cytokine profile - Seidel, Corinna L.; Gerlach, Roman; Wiedemann, Patrick; Weider, Matthias; Rodrian, Gabriele; Hader, Michael; Frey, Benjamin; Gaipl, Udo; Bozec, Aline; Cieplik, Fabian; Kirschneck, Christian; Bogdan, Christian; et al. (International Journal of Molecular Sciences, 2020)
The human oral microbiota consists of over 700 widespread taxa colonizing the oral cavity in several anatomically diverse oral niches. Lately, sequencing of the 16S rRNA genes has become an acknowledged, culture-independent method to characterize the oral microbiota. However, only a small amount of data are available concerning microbial differences between oral niches in periodontal health and disease. In the context of periodontitis, the cytokine expression in the gingival crevicular fluid has been studied in detail, whereas little is known about the cytokine profile in hard and soft tissue biofilms. In order to characterize oral niches in periodontal health, the oral microbiota and cytokine pattern were analyzed at seven different sites (plaque (P), gingival crevicular fluid (GCF), saliva (S), tongue (T), hard palate (HP), cheek (C) and sublingual area (U)) of 20 young adults using next-generation sequencing and multiplex immunoassays. Site-specific microbial compositions were detected, which clustered into three distinct metaniches (“P-GCF”, “S-T-HP” and “C-U”) and were associated with niche-/metaniche-specific cytokine profiles. Our findings allow the definition of distinct metaniches according to their microbial composition, partly reflected by their cytokine profile, and provide new insights into microenvironmental similarities between anatomical diverse oral niches.
CRIS-Team Scopus Importer:2020-11-20
Keywords: Cytokine profile; Metaniches; Multiplex immunoassay; Next-generation sequencing; Oral biofilms and fluids; Oral microbiota; Oral niches

Definition of a new blood cell count score for early survival prediction for non-small cell lung cancer patients treated with atezolizumab: Integrated analysis of four multicenter clinical trials - Zhou, Jian-Guo; Wong, Ada Hang-Heng; Wang, Haitao; Jin, Su-Han; Tan, Fangya; Chen, Yu-Zhong; He, Si-Si; Shen, Gang; Frey, Benjamin; Fietkau, Rainer; Hecht, Markus; Carr, Shamus R.; et al. (Frontiers in Immunology, 2022)
Importance: Blood cell count test (BCT) is a robust method that provides direct quantification of various types of immune cells to reveal the immune landscape to predict atezolizumab treatment outcomes for clinicians to decide the next phase of treatment. Objective: This study aims to define a new BCTscore model to predict atezolizumab treatment benefits in non-small lung cell cancer (NSCLC) patients. Design, Setting, and Participants: This study analyzed four international, multicenter clinical trials (OAK, BIRCH, POPLAR, and FIR trials) to conduct post-hoc analyses of NSCLC patients undergoing atezolizumab (anti–PD-L1) single-agent treatment (n = 1,479) or docetaxel single-agent treatment (n = 707). BCT was conducted at three time points: pre-treatment (T1), the first day of treatment cycle 3 (T2), and first day of treatment cycle 5 (T3). Univariate and multivariate Cox regression analyses were conducted to identify early BCT biomarkers to predict atezolizumab treatment outcomes in NSCLC patients. Main Outcomes and Measures: Overall survival (OS) was used as the primary end point, whereas progression-free survival (PFS) according to Response Evaluation Criteria in Solid Tumors (RECIST), clinical benefit (CB), and objective response rate (ORR) were used as secondary end points. Results: The BCT biomarkers of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) at time point T3 and neutrophil-to-monocyte ratio (NMR) at time point T2 with absolute cutoff values of NLR_T3 = 5, PLR_T3 = 180, and NMR_T2 = 6 were identified as strong predictive biomarkers for atezolizumab (Ate)–treated NSCLC patients in comparison with docetaxel (Dtx)–treated patients regarding OS (BCTscore low risk: HR Ate vs. Dtx = 1.54 (95% CI: 1.04–2.27), P = 0.031; high risk: HR Ate vs. Dtx = 0.84 (95% CI: 0.62–1.12), P = 0.235). The identified BCTscore model showed better OS AUC in the OAK (AUC12month = 0.696), BIRCH (AUC12month = 0.672) and POPLAR+FIR studies (AUC12month = 0.727) than that of each of the three single BCT biomarkers. Conclusion and Relevance: The BCTscore model is a valid predictive and prognostic biomarker for early survival prediction in atezolizumab-treated NSCLC patients.
CRIS-Team Scopus Importer:2022-09-30
Keywords: atezolizumab; biomarker; blood cell count; clinical trial; NSCLC

Definitive chemoradiotherapy of locally advanced head and neck cancer in combination with immune checkpoint inhibition-new concepts required - Hecht, Markus; Fietkau, Rainer; Gaipl, Udo (Strahlentherapie und Onkologie, 2021)
CRIS-Team WoS Importer:2021-12-17

Defnitive Radiochemotherapy with and without regional Deep Hyperthermia of Bladder Carcinoma in elderly Patients - Siavooshhaghighi, H.; Putz, Florian; Gryc, Thomas; Mansoorian, S.; Filimonova, Irina; Fietkau, Rainer; Ott, Oliver (STRAHLENTHERAPIE UND ONKOLOGIE, 2020)
CRIS-Team WoS Importer:2020-10-02

DEGRO guideline for personalized radiotherapy of brain metastases and leptomeningeal carcinomatosis in patients with breast cancer - Borm, Kai J.; Behzadi, Sophie T.; Hörner-Rieber, Juliane; Krug, David; Baumann, Rene; Corradini, Stefanie; Duma, Marciana Nona; Dunst, Jürgen; Fastner, Gerd; Feyer, Petra; Fietkau, Rainer; Haase, Wulf; et al. (Strahlentherapie und Onkologie, 2024)
Purpose: The aim of this review was to evaluate the existing evidence for radiotherapy for brain metastases in breast cancer patients and provide recommendations for the use of radiotherapy for brain metastases and leptomeningeal carcinomatosis. Materials and methods: For the current review, a PubMed search was conducted including articles from 01/1985 to 05/2023. The search was performed using the following terms: (brain metastases OR leptomeningeal carcinomatosis) AND (breast cancer OR breast) AND (radiotherapy OR ablative radiotherapy OR radiosurgery OR stereotactic OR radiation). Conclusion and recommendations: Despite the fact that the biological subtype of breast cancer influences both the occurrence and relapse patterns of breast cancer brain metastases (BCBM), for most scenarios, no specific recommendations regarding radiotherapy can be made based on the existing evidence. For a limited number of BCBM (1–4), stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (SRT) is generally recommended irrespective of molecular subtype and concurrent/planned systemic therapy. In patients with 5–10 oligo-brain metastases, these techniques can also be conditionally recommended. For multiple, especially symptomatic BCBM, whole-brain radiotherapy (WBRT), if possible with hippocampal sparing, is recommended. In cases of multiple asymptomatic BCBM (≥ 5), if SRS/SRT is not feasible or in disseminated brain metastases (> 10), postponing WBRT with early reassessment and reevaluation of local treatment options (8–12 weeks) may be discussed if a HER2/Neu-targeting systemic therapy with significant response rates in the central nervous system (CNS) is being used. In symptomatic leptomeningeal carcinomatosis, local radiotherapy (WBRT or local spinal irradiation) should be performed in addition to systemic therapy. In patients with disseminated leptomeningeal carcinomatosis in good clinical condition and with only limited or stable extra-CNS disease, craniospinal irradiation (CSI) may be considered. Data regarding the toxicity of combining systemic therapies with cranial and spinal radiotherapy are sparse. Therefore, no clear recommendations can be given, and each case should be discussed individually in an interdisciplinary setting.
CRIS-Team Scopus Importer:2024-04-05
Keywords: Craniospinal irradiation; Molecular profile; Neurocognitive side effects; Radiosurgery; Whole-brain radiotherapy

DEGRO guidelines for the radiotherapy of non-malignant disorders : Part II: Painful degenerative skeletal disorders - Ott, Oliver J.; Niewald, Marcus; Weitmann, Hajo-Dirk; Jacob, Ingrid; Adamietz, Irenaeus A.; Schaefer, Ulrich; Keilholz, Ludwig; Heyd, Reinhard; Muecke, Ralph (Strahlentherapie und Onkologie, 2015)
The purpose of this article is to summarize the updated DEGRO consensus S2e guideline recommendations for the treatment of benign painful degenerative skeletal disorders with low-dose radiotherapy.This overview reports on the role of low-dose radiotherapy in the treatment of enthesiopathies (shoulder syndrome, trochanteric bursitis, plantar fasciitis, and elbow syndrome) and painful arthrosis (knee, hip, hand, and finger joints). The most relevant aspects of the DEGRO S2e Consensus Guideline Radiation Therapy of Benign Diseases 2014 regarding diagnostics, treatment decision, dose prescription as well as performance of radiotherapy and results are summarized.For all indications mentioned above, retrospective and some prospective analyses have shown remarkable effects in terms of pain relief. Nevertheless, the Level of Evidence (LoE) and the Grade of Recommendation (GR) vary: LoE 1b-4 and GR A-C.Low-dose radiotherapy for painful degenerative skeletal disorders is effective in the majority of the patients and therefore it may be a reasonable therapeutic alternative when simple and non-invasive methods have been used without persistent success. For all discussed entities, single fraction doses of 0.5-1.0 Gy and total doses of 3.0-6.0 Gy/series applied with 2-3 fractions per week are recommended.
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DEGRO practical guideline for central nervous system radiation necrosis part 1: classification and a multistep approach for diagnosis - Bernhardt, Denise; Koenig, Laila; Grosu, Anca; Wiestler, Benedikt; Rieken, Stefan; Wick, Wolfgang; Gempt, Jens; Krieg, Sandro M.; Schmidt-Graf, Friederike; Sahm, Felix; Meyer, Bernhard; Krause, Bernd J.; et al. (Strahlentherapie und Onkologie, 2022)
Purpose: The Working Group for Neuro-Oncology of the German Society for Radiation Oncology in cooperation with members of the Neuro-Oncology Working Group of the German Cancer Society aimed to define a practical guideline for the diagnosis and treatment of radiation-induced necrosis (RN) of the central nervous system (CNS). Methods: Panel members of the DEGRO working group invited experts, participated in a series of conferences, supplemented their clinical experience, performed a literature review, and formulated recommendations for medical treatment of RN including bevacizumab in clinical routine. Conclusion: Diagnosis and treatment of RN requires multidisciplinary structures of care and defined processes. Diagnosis has to be made on an interdisciplinary level with the joint knowledge of a neuroradiologist, radiation oncologist, neurosurgeon, neuropathologist, and neuro-oncologist. A multistep approach as an opportunity to review as many characteristics as possible to improve diagnostic confidence is recommended. Additional information about radiotherapy (RT) techniques is crucial for the diagnosis of RN. Misdiagnosis of untreated and progressive RN can lead to severe neurological deficits. In this practice guideline, we propose a detailed nomenclature of treatment-related changes and a multistep approach for their diagnosis.
CRIS-Team Scopus Importer:2022-09-16
Keywords: Bevacizumab; Brain metastases; Glioma; Radioation necrosis; Reirradiation

DEGRO practical guideline for central nervous system radiation necrosis part 2: treatment - Bernhardt, Denise; Koenig, Laila; Grosu, Anca-L; Rieken, Stefan; Krieg, Sandro M.; Wick, Wolfgang; Wiestler, Benedikt; Schmidt-Graf, Friederike; Sahm, Felix; Gempt, Jens; Meyer, Bernhard; Krause, Bernd J.; et al. (Strahlentherapie und Onkologie, 2022)
Purpose The Working Group for Neurooncology of the German Society for Radiation Oncology (DEGRO; AG NRO) in cooperation with members of the Neurooncological Working Group of the German Cancer Society (DKG-NOA) aimed to define a practical guideline for the diagnosis and treatment of radiation-induced necrosis (RN) of the central nervous system (CNS). Methods Panel members of the DEGRO working group invited experts, participated in a series of conferences, supplemented their clinical experience, performed a literature review, and formulated recommendations for medical treatment of RN, including bevacizumab, in clinical routine. Conclusion Diagnosis and treatment of RN requires multidisciplinary structures of care and defined processes. Diagnosis has to be made on an interdisciplinary level with the joint knowledge of a neuroradiologist, radiation oncologist, neurosurgeon, neuropathologist, and neurooncologist. If the diagnosis of blood-brain barrier disruptions (BBD) or RN is likely, treatment should be initiated depending on the symptoms, location, and dynamic of the lesion. Multiple treatment options are available (such as observation, surgery, steroids, and bevacizumab) and the optimal approach should be discussed in an interdisciplinary setting. In this practice guideline, we offer detailed treatment strategies for various scenarios.
CRIS-Team WoS Importer:2022-09-09

DEGRO practical guideline for partial-breast irradiation - Strnad, Vratislav; Krug, D.; Sedlmayer, F.; Piroth, M. D.; Budach, W.; Baumann, R.; Feyer, P.; Duma, M. N.; Haase, W.; Harms, W.; Hehr, T.; Fietkau, Rainer; et al. (Strahlentherapie und Onkologie, 2020)
Purpose: This consensus statement from the Breast Cancer Working Group of the German Society for Radiation Oncology (DEGRO) aims to define practical guidelines for accelerated partial-breast irradiation (APBI). Methods: Recent recommendations for relevant aspects of APBI were summarized and a panel of experts reviewed all the relevant literature. Panel members of the DEGRO experts participated in a series of conferences, supplemented their clinical experience, performed a literature review, and formulated recommendations for implementing APBI in clinical routine, focusing on patient selection, target definition, and treatment technique. Results: Appropriate patient selection, target definition for different APBI techniques, and basic rules for appropriate APBI techniques for clinical routine outside of clinical trials are described. Detailed recommendations for APBI in daily practice, including dose constraints, are given. Conclusion: Guidelines are mandatory to assure optimal results of APBI using different techniques.
CRIS-Team Scopus Importer:2020-05-12
Keywords: APBI; Breast cancer; Early breast cancer; Guideline; Partial breast irradiation

DEGRO practical guidelines for radiotherapy of breast cancer IV: radiotherapy following mastectomy for invasive breast cancer - Wenz, Frederik; Sperk, Elena; Budach, Wilfried; Dunst, Juergen; Feyer, Petra; Fietkau, Rainer; Haase, Wulf; Harms, Wolfgang; Piroth, Marc D.; Sautter-Bihl, Marie-Luise; Sedlmayer, Felix; Souchon, Rainer; et al. (Strahlentherapie und Onkologie, 2014)
Since the last recommendations from the Breast Cancer Expert Panel of the German Society for Radiation Oncology (DEGRO) in 2008, evidence for the effectiveness of postmastectomy radiotherapy (PMRT) has grown. This growth is based on updates of the national S3 and international guidelines, as well as on new data and meta-analyses. New aspects were considered when updating the DEGRO recommendations.The authors performed a comprehensive survey of the literature. Data from recently published (meta-)analyses, randomized clinical trials and international cancer societies' guidelines yielding new aspects compared to 2008 were reviewed and discussed. New aspects were included in the current guidelines. Specific issues relating to particular PMRT constellations, such as the presence of risk factors (lymphovascular invasion, blood vessel invasion, positive lymph node ratio >20 %, resection margins <3 mm, G3 grading, young age/premenopausal status, extracapsular invasion, negative hormone receptor status, invasive lobular cancer, size >2 cm or a combination of >= 2 risk factors) and 1-3 positive lymph nodes are emphasized.The evidence for improved overall survival and local control following PMRT for T4 tumors, positive resection margins, >3 positive lymph nodes and in T3 N0 patients with risk factors such as lymphovascular invasion, G3 grading, close margins, and young age has increased. Recently identified risk factors such as invasive lobular subtype and negative hormone receptor status were included. For patients with 1-3 positive lymph nodes, the recommendation for PMRT has reached the 1a level of evidence.PMRT is mandatory in patients with T4 tumors and/or positive lymph nodes and/or positive resection margins. PMRT should be strongly considered in patients with T3 N0 tumors and risk factors, particularly when two or more risk factors are present.
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DEGRO practical guidelines for radiotherapy of breast cancer VI: therapy of locoregional breast cancer recurrences - Harms, Wolfgang; Budach, W.; Dunst, J.; Feyer, P.; Fietkau, Rainer; Haase, W.; Krug, D.; Piroth, M. D.; Sautter-Bihl, Marie-Luise; Sedlmayer, F.; Souchon, R.; Wenz, F.; et al. (Strahlentherapie und Onkologie, 2016)
To update the practical guidelines for radiotherapy of patients with locoregional breast cancer recurrences based on the current German interdisciplinary S3 guidelines 2012.A comprehensive survey of the literature using the search phrases "locoregional breast cancer recurrence", "chest wall recurrence", "local recurrence", "regional recurrence", and "breast cancer" was performed, using the limits "clinical trials", "randomized trials", "meta-analysis", "systematic review", and "guidelines".Patients with isolated in-breast or regional breast cancer recurrences should be treated with curative intent. Mastectomy is the standard of care for patients with ipsilateral breast tumor recurrence. In a subset of patients, a second breast conservation followed by partial breast irradiation (PBI) is an appropriate alternative to mastectomy. If a second breast conservation is performed, additional irradiation should be mandatory. The largest reirradiation experience base exists for multicatheter brachytherapy; however, prospective clinical trials are needed to clearly define selection criteria, long-term local control, and toxicity. Following primary mastectomy, patients with resectable locoregional breast cancer recurrences should receive multimodality therapy including systemic therapy, surgery, and radiation +/- hyperthermia. This approach results in high local control rates and long-term survival is achieved in a subset of patients. In radiation-naive patients with unresectable locoregional recurrences, radiation therapy is mandatory. In previously irradiated patients with a high risk of a second local recurrence after surgical resection or in patients with unresectable recurrences, reirradiation should be strongly considered. Indication and dose concepts depend on the time interval to first radiotherapy, presence of late radiation effects, and concurrent or sequential systemic treatment. Combination with hyperthermia can further improve tumor control. In patients with isolated axillary or supraclavicular recurrence, durable disease control is best achieved with multimodality therapy including surgery and radiotherapy. Radiation therapy significantly improves local control and should be applied whenever feasible.
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DEGRO practical guidelines for radiotherapy of breast cancer V: Therapy for locally advanced and inflammatory breast cancer, as well as local therapy in cases with synchronous distant metastases - Budach, Wilfried; Matuschek, Christiane; Bölke, Edwin; Dunst, Jürgen; Feyer, Petra; Fietkau, Rainer; Haase, Wulf; Harms, Wolfgang; Piroth, Marc D.; Sautter-Bihl, Marie-Luise; Sedlmayer, Felix; Souchon, Rainer; et al. (Strahlentherapie und Onkologie, 2015)
The purpose of this work is to give practical guidelines for radiotherapy of locally advanced, inflammatory and metastatic breast cancer at first presentation.A comprehensive survey of the literature using the search phrases "locally advanced breast cancer", "inflammatory breast cancer", "breast cancer and synchronous metastases", "de novo stage IV and breast cancer", and "metastatic breast cancer" and "at first presentation" restricted to "clinical trials", "randomized trials", "meta-analysis", "systematic review", and "guideline" was performed and supplemented by using references of the respective publications. Based on the German interdisciplinary S3 guidelines, updated in 2012, this publication addresses indications, sequence to other therapies, target volumes, dose, and fractionation of radiotherapy.International and national guidelines are in agreement that locally advanced, at least if regarded primarily unresectable and inflammatory breast cancer should receive neoadjuvant systemic therapy first, followed by surgery and radiotherapy. If surgery is not amenable after systemic therapy, radiotherapy is the treatment of choice followed by surgery, if possible. Surgery and radiotherapy should be administered independent of response to neoadjuvant systemic treatment. In patients with a de novo diagnosis of breast cancer with synchronous distant metastases, surgery and radiotherapy result in considerably better locoregional tumor control. An improvement in survival has not been consistently proven, but may exist in subgroups of patients.Radiotherapy is an important part in the treatment of locally advanced and inflammatory breast cancer that should be given to all patients regardless to the intensity and effect of neoadjuvant systemic treatment and the extent of surgery. Locoregional radiotherapy in patients with primarily distant metastatic disease should be prescribed on an individual basis.
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DEGRO practical guidelines for radiotherapy of non-malignant disorders: Part I: physical principles, radiobiological mechanisms, and radiogenic risk - Reichl, Berthold; Block, Andreas; Schäfer, Ulrich; Bert, Christoph; Müller, Reinhold; Jung, Horst; Rödel, Franz (Strahlentherapie und Onkologie, 2015)
Synopsis of the introductory paragraph of the DEGRO consensus S2e-guideline recommendations for the radiotherapy of benign disorders, including physical principles, radiobiological mechanisms, and radiogenic risk.This work is based on the S2e-guideline recommendations published November 14, 2013. The basic principles of radiation physics and treatment delivery, evaluation of putative underlying radiobiological mechanisms, and the assessment of genetic and cancer risk following low-dose irradiation will be presented.Radiation therapy of benign diseases is performed according to similar physical principles as those governing treatment of malignant diseases in radiation oncology, using the same techniques and workflows. These methods comprise usage of orthovoltage X-ray units, gamma irradiation facilities, linear accelerators (LINACs), and brachytherapy. Experimental in vitro and in vivo models recently confirmed the clinically observed anti-inflammatory effect of low-dose X-irradiation, and implicated a multitude of radiobiological mechanisms. These include modulation of different immunological pathways, as well as the activities of endothelial cells, mono- and polymorphonuclear leukocytes, and macrophages. The use of effective dose for radiogenic risk assessment and the corresponding tumor incidence rate of 5.5%/Sv are currently controversially discussed. Some authors argue that the risk of radiation-induced cancers should be estimated on the basis of epidemiological data. However, such data are rarely available at present and associated with high variability.Current radiobiological studies clearly demonstrate a therapeutic effectiveness of radiation therapy used to treat benign diseases and implicate various molecular mechanisms. Radiogenic risks should be taken into account when applying radiation treatment for benign diseases.
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DEGRO practical guidelines: radiotherapy of breast cancer III–radiotherapy of the lymphatic pathways - Sautter-Bihl, M. -L.; Sedlmayer, F.; Budach, W.; Dunst, Juergen; Feyer, P.; Sauer, Rolf; Fussl, C.; Haase, W.; Harms, W.; Piroth, M. D.; Souchon, R.; Wenz, F.; et al. (Strahlentherapie und Onkologie, 2014)
The purpose of this work is to update the practical guidelines for adjuvant radiotherapy of the regional lymphatics of breast cancer published in 2008 by the breast cancer expert panel of the German Society of Radiation Oncology (DEGRO).A comprehensive survey of the literature concerning regional nodal irradiation (RNI) was performed using the following search terms: "breast cancer", "radiotherapy", "regional node irradiation". Recent randomized trials were analyzed for outcome as well as for differences in target definition. Field arrangements in the different studies were reproduced and superimposed on CT slices with individually contoured node areas. Moreover, data from recently published meta-analyses and guidelines of international breast cancer societies, yielding new aspects compared to 2008, provided the basis for defining recommendations according to the criteria of evidence-based medicine. In addition to the more general statements of the German interdisciplinary S3 guidelines updated in 2012, this paper addresses indications, targeting, and techniques of radiotherapy of the lymphatic pathways after surgery for breast cancer.International guidelines reveal substantial differences regarding indications for RNI. Patients with 1-3 positive nodes seem to profit from RNI compared to whole breast (WBI) or chest wall irradiation alone, both with regard to locoregional control and disease-free survival. Irradiation of the regional lymphatics including axillary, supraclavicular, and internal mammary nodes provided a small but significant survival benefit in recent randomized trials and one meta-analysis. Lymph node irradiation yields comparable tumor control in comparison to axillary lymph node dissection (ALND), while reducing the rate of lymph edema. Data concerning the impact of 1-2 macroscopically affected sentinel node (SN) or microscopic metastases on prognosis are conflicting.Recent data suggest that the current restrictive use of RNI should be scrutinized because the risk-benefit relationship appears to shift towards an improvement of outcome.
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DEGRO practical guidelines: radiotherapy of breast cancer II: radiotherapy of non-invasive neoplasia of the breast - Souchon, R.; Sautter-Bihl, M-L; Sedlmayer, Felix; Budach, W.; Dunst, Juergen; Feyer, P.; Fietkau, Rainer; Haase, W.; Harms, W.; Wenz, F.; Sauer, Rolf (Strahlentherapie und Onkologie, 2014)
To complement and update the 2007 practice guidelines of the breast cancer expert panel of the German Society of Radiation Oncology (DEGRO) for radiotherapy (RT) of breast cancer. Owing to its growing clinical relevance, in the current version, a separate paper is dedicated to non-invasive proliferating epithelial neoplasia of the breast. In addition to the more general statements of the German interdisciplinary S3 guidelines, this paper is especially focused on indication and technique of RT in addition to breast conserving surgery.The DEGRO expert panel performed a comprehensive survey of the literature comprising recently published data from clinical controlled trials, systematic reviews as well as meta-analyses, referring to the criteria of evidence-based medicine yielding new aspects compared to 2005 and 2007. The literature search encompassed the period 2008 to September 2012 using databases of PubMed and Guidelines International Network (G-I-N). Search terms were "non invasive breast cancer", "ductal carcinoma in situ, "dcis", "borderline breast lesions", "lobular neoplasia", "radiotherapy" and "radiation therapy". In addition to the more general statements of the German interdisciplinary S3 guidelines, this paper is especially focused on indications of RT and decision making of non-invasive neoplasia of the breast after surgery, especially ductal carcinoma in situ.Among different non-invasive neoplasia of the breast only the subgroup of pure ductal carcinoma in situ (DCIS; synonym ductal intraepithelial neoplasia, DIN) is considered for further recurrence risk reduction treatment modalities after complete excision of DCIS, particularly RT following breast conserving surgery (BCS), in order to avoid a mastectomy. About half of recurrences are invasive cancers. Up to 50 % of all recurrences require salvage mastectomy. Randomized clinical trials and a huge number of mostly observational studies have unanimously demonstrated that RT significantly reduces recurrence risks of ipsilateral DCIS as well as invasive breast cancer independent of patient age in all subgroups. The recommended total dose is 50 Gy administered as whole breast irradiation (WBI) in single fractions of 1.8 or 2.0 Gy given on 5 days weekly. Retrospective data indicate a possible beneficial effect of an additional tumor bed boost for younger patients. Prospective clinical trials of different dose-volume concepts (hypofractionation, accelerated partial breast irradiation, boost radiotherapy) are still ongoing.Postoperative radiotherapy permits breast conservation for the majority of women by halving local recurrence as well as reducing progression rates into invasive cancer. New data confirmed this effect in all patient subsets-even in low risk subgroups (LoE 1a).
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Deletion of the receptor tyrosine kinase Tyro3 inhibits synovial hyperplasia and bone damage in arthritis - Ruiz-Heiland, Gisela; Zhao, Yi; Derer, Anja; Braun, Timm; Engelke, Klaus; Neumann, Elena; Mueller-Ladner, Ulf; Liu, Yi; Zwerina, Jochen; Schett, Georg (Annals of the Rheumatic Diseases, 2014)
To test whether the tyrosine kinase Tyro3 affects arthritis. Tyro3, the ligand of growth arrest-specific protein 6 (GAS6) is a receptor tyrosine kinase involved in cell survival. Tyro3 and GAS6 are expressed in the arthritic synovium, and in vitro studies have shown their role in osteoclast differentiation.Bone was assessed by micro CT and histomorphometry in Tyro3-deficient (Tyro3(-/-)) and wild-type mice. Arthritis was induced in both genotypes, and Gas6 level was measured by ELISA. Synovitis, synovial hyperplasia, bone erosion, osteoclast activation and osteoclast gene expression were assessed by histomorphometry and reverse transcriptase-PCR, respectively. In vitro osteoclast differentiation assays were performed in Tyro3(-/-) and wild-type mice. Furthermore, effects of Tyro3 and GAS6 on human synovial fibroblast proliferation and osteoclastogenesis were assessed in human cells.Tyro3(-/-) mice had significantly higher bone mass than wild-type littermates. Induction of arthritis increased GAS6 serum levels. Arthritic Tyro3(-/-) mice showed less synovial hyperplasia, osteoclast numbers and bone damage compared with controls. In vivo expression of osteoclast-associated receptor and receptor activator of nuclear factor-?B and in vitro osteoclastogenesis were impaired in Tyro3(-/-) mice. GAS6 also induced synovial fibroblast proliferation and osteoclast differentiation in human cells in Tyro3-dependent manner.These findings indicate that Tyro3 is a critical signal for synovial hyperplasia, osteoclast differentiation and bone erosion during arthritis. GAS6 and Tyro3 therefore constitute therapeutic targets to inhibit synovial hyperplasia and associated bone erosion.
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Dense feature-based motion estimation in MV fluoroscopy during dynamic tumor tracking treatment: preliminary study on reduced aperture and partial occlusion handling - Serpa, Marco; Bert, Christoph (Physics in Medicine and Biology, 2020)
Quality assurance solutions to complement available motion compensation technologies are central for their safe routine implementation and success of treatment. This work presents a dense feature-based method for soft-tissue tumor motion estimation in megavoltage (MV) beam's-eye-view (BEV) projections for potential intra-treatment monitoring during dynamic tumor tracking (DTT). Dense sampling and matching principles were employed to track a gridded set of features landmarks (FLs) in MV-BEV projections and estimate tumor motion, capable to overcome reduced field aperture and partial occlusion challenges. The algorithm's performance was evaluated by retrospectively applying it to fluoroscopic sequences acquired at similar to 2 frames s(-1) (fps) for a dynamic phantom and two lung stereotactic body radiation therapy (SBRT) patients treated with DTT on the Vero SBRT system. First, a field-specific train image is initialized by sampling the tumor region at, S, pixel intervals on a grid using a representative frame from a stream of query frames. Sampled FLs are locally characterized in the form of descriptor vectors and geometric attributes representing the target. For motion tracking, subsequent query frames are likewise sampled, corresponding feature descriptors determined, and then patch-wise matched to the training set based on their descriptors and geometric relationships. FLs with high correspondence are pruned and used to estimate tumor displacement. In scenarios of partial occlusions, position is estimated from the set of correctly (visible) FLs on past observations. Reconstructed trajectories were benchmarked against ground-truth manual tracking using the root-mean-square (RMS) as a metric of positional accuracy. A total of 19 fluoroscopy sequences were analyzed. This included scenarios of field aperture obstruction during three-dimensional conformal, as well as step-and-shoot intensity modulated radiotherapy (IMRT) delivery assisted with DTT. The algorithm resolved target motion satisfactorily. The RMS was <1.2 mm and <1.8 mm for the phantom and the clinical dataset, respectively. Dense tracking showed promising results to overcome localization challenges at the field penumbra and partial obstruction by multi-leaf collimator (MLC). Motion retrieval was possible in similar to 66% of the control points studied. In addition to MLC obstruction, changes in the external/internal breathing dynamics and baseline drifts were a major source of estimation bias. Dense feature-based tracking is a viable alternative. The algorithm is rotation-/scale-invariant and robust to photometric changes. Tracking multiple features may help overcome partial occlusion challenges by the MLC. This in turn opens up new possibilities for motion detection and intra-treatment monitoring during IMRT and potentially VMAT.
CRIS-Team WoS Importer:2021-01-15

Detailed in vitro analyses of the impact of multimodal cancer therapy with hyperthermia and radiotherapy on the immune phenotype of human glioblastoma cells - Stoll, Eileen; Hader, Michael; Rückert, Michael; Weissmann, Thomas; Lettmaier, Sebastian; Putz, Florian; Hecht, Markus; Fietkau, Rainer; Rosin, Andreas; Frey, Benjamin; Gaipl, Udo (International Journal of Hyperthermia, 2022)
Purpose Improvements of heat-delivery systems have led to hyperthermia (HT) being increasingly recognized as an adjunct treatment modality also for brain tumors. But how HT affects the immune phenotype of glioblastoma cells is only scarcely known. Materials and Methods We therefore investigated the effect of in vitro HT, radiotherapy (RT), and the combination of both (RHT) on cell death modalities, immune checkpoint molecule (ICM) expression and release of the danger signal HSP70 of two human glioblastoma cell lines (U87 and U251) by using multicolor flow cytometry and ELISA. Hyperthermia was performed once or twice for 60-minute sessions reaching temperatures of 39 degrees C, 41 degrees C, and 44 degrees C, respectively. RT was administered with 5 x 2 Gy. Results A hyperthermia chamber for cell culture t-flasks regulating the temperature via a contact sensor was developed. While the glioblastoma cells were rather radioresistant, particularly in U251 cells, the combination of RT with HT significantly increased the percentage of apoptotic and necrotic cells for all temperatures examined and for both, single and double HT application. In line with that, an increased release of HSP 70 was seen only in U251 cells, mainly following treatment with HT at temperatures of 44 degrees C alone or in combination with RT. In contrast, immune suppressive (PD-L1, PD-L2, HVEM) and immune stimulatory (ICOS-L, CD137-L and Ox40-L) ICMs were significantly increased mostly on U87 cells, and particularly after RHT with 41 degrees C. Conclusions Individual assessment of the glioblastoma immune cell phenotype with regard to the planned treatment is mandatory to optimize multimodal radio-immunotherapy protocols including HT.
CRIS-Team WoS Importer:2022-06-24
Keywords: Hyperthermia; radiotherapy; immune checkpoint molecules; danger signals; glioblastoma; multimodal cancer therapy

Detection of Human Cytomegalovirus (HCMV) in monocytic Cells of the peripheral Blood in Glioma Patients during Radio (chemo) Therapy - Bäumler, Monika; Becker, Ina; Frey, Benjamin; Pohn, Anna; Winkler, Thomas; Fietkau, Rainer; Gaipl, Udo (STRAHLENTHERAPIE UND ONKOLOGIE, 2021)
CRIS-Team WoS Importer:2021-07-16

Deterioration of Health-Related Quality of Life Scores under Treatment Predicts Longer Survival - Jörling, Maike; Rutzner, Sandra; Hecht, Markus; Fietkau, Rainer; Distel, Luitpold (BioMed Research International, 2020)
Objectives: Baseline health-related quality of life (HRQoL) scores predict survival, which has already been demonstrated in various studies. However, we were interested in whether changes in baseline scores during treatment are also significant predictors of survival. Methods and Materials: We analysed the data of 400 consecutive cancer patients receiving radiochemotherapy. Leading diagnoses were head and neck cancer (34.5%), rectal cancer (24.5%), and lung cancer (13%). HRQoL was studied at baseline, six weeks after therapy and after each completed year after the start of therapy until drop out of the study using the EORTC QLQ-C30 questionnaire. The change score was calculated as the baseline score subtracted from the score after therapy. Statistics included Kaplan-Meier estimates and Cox regression. Results: High global health status (p = 0.005) and low pain scores (p = 0.040) at baseline were related to favourable overall survival. Change scores of role functioning (p = 0.027), global health status (p < 0.018), and pain (p < 0.001) were predictive of overall survival. Pain was the superior predictor of survival (p = 0.001) among all variables and QoL scores studied by multivariate analysis. A deterioration in pain was associated with a 2.8 times higher chance of survival (HR 0.36). Conclusions: Deterioration of HRQoL baseline pain score by cancer treatment is a favourable and superior prognostic factor for survival.
CRIS-Team Scopus Importer:2020-09-11

Determinants Affecting the Clinical Implementation of a Molecularly Informed Molecular Tumor Board Recommendation: Experience from a Tertiary Cancer Center. - Tögel, Lars; Schubart, Christoph; Lettmaier, Sebastian; Neufert, Clemens; Hoyer, Juliane; Wolff, Kerstin; Moskalev, Evgeny; Stöhr, Robert; Agaimy, Abbas; Wiesmann da Silva Reis, André; Wullich, Bernd; Mackensen, Andreas; et al. (Cancers, 2023)
Molecular Tumor Boards (MTBs) converge state-of-the-art next-generation sequencing (NGS) methods with the expertise of an interdisciplinary team consisting of clinicians, pathologists, human geneticists, and molecular biologists to provide molecularly informed guidance in clinical decision making to the treating physician. In the present study, we particularly focused on elucidating the factors impacting on the clinical translation of MTB recommendations, utilizing data generated from gene panel mediated comprehensive genomic profiling (CGP) of 554 patients at the MTB of the Comprehensive Cancer Center Erlangen, Germany, during the years 2016 to 2020. A subgroup analysis of cases with available follow-up data (n = 332) revealed 139 cases with a molecularly informed MTB recommendation, which was successfully implemented in the clinic in 44 (31.7%) of these cases. Here, the molecularly matched treatment was applied in 45.4% (n = 20/44) of cases for ≥6 months and in 25% (n = 11/44) of cases for 12 months or longer (median time to treatment failure, TTF: 5 months, min: 1 month, max: 38 months, ongoing at data cut-off). In general, recommendations were preferentially implemented in the clinic when of high (i.e., tier 1) clinical evidence level. In particular, this was the case for MTB recommendations suggesting the application of PARP, PIK3CA, and IDH1/2 inhibitors. The main reason for non-compliance to the MTB recommendation was either the application of non-matched treatment modalities (n = 30)/stable disease (n = 7), or deteriorating patient condition (n = 22)/death of patient (n = 9). In summary, this study provides an insight into the factors affecting the clinical implementation of molecularly informed MTB recommendations, and careful considerations of these factors may guide future processes of clinical decision making.
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Keywords: Molecular Tumor Board; clinical decision making; precision medicine; molecular pathology; real-world data; cancer care

Deutsche Gesellschaft für Radioonkologie (DEGRO) mahnt stationäre strahlentherapeutische Versorgung an: Stellungnahme zu einem Urteil des Bundessozialgerichts vom 29.08.2023 zur Erbringung stationärer strahlentherapeutischer Leistungen - Fietkau, Rainer; Höller, Ulrike; van Kampen, Michael; Krause, Mechthild; Petersen, Cordula; Vordermark, Dirk (Strahlentherapie und Onkologie, 2023)
CRIS-Team Scopus Importer:2023-11-03

Development and clinical implementation of a digital system for risk assessments for radiation therapy - Kornek, Dominik; Menichelli, David; Leske, Jörg; Hofmann, Michael; Antkiewicz, David; Brandt, Tobias; Ott, Oliver; Lotter, Michael; Lang-Welzenbach, Marga; Fietkau, Rainer; Bert, Christoph (Zeitschrift für Medizinische Physik, 2023)
Before introducing new treatment techniques, an investigation of hazards due to unintentional radiation exposures is a reasonable activity for proactively increasing patient safety. As dedicated software is scarce, we developed a tool for risk assessment to design a quality management program based on best practice methods, i.e., process mapping, failure modes and effects analysis and fault tree analysis. Implemented as a web database application, a single dataset was used to describe the treatment process and its failure modes. The design of the system and dataset allowed failure modes to be represented both visually as fault trees and in a tabular form. Following the commissioning of the software for our department, previously conducted risk assessments were migrated to the new system after being fully re-assessed which revealed a shift in risk priorities. Furthermore, a weighting factor was investigated to bring risk levels of the migrated assessments into perspective. The compensation did not affect high priorities but did re-prioritize in the midrange of the ranking. We conclude that the tool is suitable to conduct multiple risk assessments and concomitantly keep track of the overall quality management activities.
CRIS-Team Scopus Importer:2023-09-15
Keywords: Failure modes and effects analysis (FMEA); Fault tree analysis (FTA); Process throughput; Radiation therapy; Risk analysis; Risk-based quality management

Development and Validation of a Gene Signature for Prediction of Relapse in Stage I Testicular Germ Cell Tumors - Zhou, Jian Guo; Yang, Jie; Jin, Su Han; Xiao, Siyu; Shi, Lei; Zhang, Ting You; Ma, Hu; Gaipl, Udo (Frontiers in Oncology, 2020)
Background: Testicular germ cell tumors (TGCTs) are commonly diagnosed tumors in young men. However, a satisfactory approach to predict relapse of stage I TGCTs is still lacking. Therefore, this study aimed to develop a robust risk score model for stage I TGCTs. Method: RNA-sequence data of stage I TGCTs and normal testis samples were downloaded and analyzed to identify different expression genes. Gene-based prognostic model was constructed in The Cancer Genome Atlas (TCGA) using least absolute shrinkage and selection operator (LASSO) regression analysis and validated in GSE99420 dataset. Potential biological functions of the genes in prognostic model were determined via Gene Set Enrichment Analysis (GSEA) between high-risk and low-risk patients. Results: A total of 9,391 differentially expressed genes and 84 prognosis-related genes were identified. An eight-gene-based risk score model was constructed to divide patients into high or low risk of relapse. The low-risk patients had a significantly better relapse-free survival (RFS) than high-risk patients in both training and validation cohorts (HR = 0.129, 95% CI = 0.059–0.284, P < 0.001; HR = 0.277, 95% CI = 0.116–0.661, P = 0.004, respectively). The area under the receiver operating characteristic curve (AUC) values at 5 years was 0.805 and 0.724 in the training and validation cohorts, respectively. Functional enrichment analyses showed that DNA replication, ribosome, cell cycle, and TGF-beta signaling pathway may contribute to the relapse process. Conclusion: In summary, our analysis provided a novel eight-gene signature that could predict RFS in stage I TGCT patients.
CRIS-Team Scopus Importer:2020-08-28
Keywords: GEO; relapse; risk score model; testicular germ cell tumors; The Cancer Genome Atlas

Development and Validation of an RNA-Seq-Based Prognostic Signature in Neuroblastoma - Zhou, Jian-Guo; Liang, Bo; Jin, Su-Han; Liao, Hui-Ling; Du, Guo-Bo; Cheng, Long; Ma, Hu; Gaipl, Udo (Frontiers in Oncology, 2019)
Objective: The stratification of neuroblastoma (NBL) prognosis remains difficult. RNA-based signatures might be able to predict prognosis, but independent cross-platform validation is still rare. Methods: RNA-Seq-based profiles from NBL patients were acquired and then analyzed. The RNA-Seq prognostic index (RPI) and the clinically adjusted RPI (RCPI) were successively established in the training cohort (TARGET-NBL) and then verified in the validation cohort (GSE62564). Survival prediction was assessed using a time-dependent receiver operating characteristic (ROC) curve and area under the ROC curve (AUC). Functional enrichment analysis of the genes was conducted using bioinformatics methods. Results: In the training cohort, 10 gene pairs were eventually integrated into the RPI. In both cohorts, the high-risk group had poor overall survival (OS) (P < 0.001 and P < 0.001, respectively) and favorable event-free survival (EFS) (P = 0.00032 and P = 0.06, respectively). ROC curve analysis also showed that the RPI predicted OS (60 month AUC values of 0.718 and 0.593, respectively) and EFS (60 month AUC values of 0.627 and 0.852, respectively) well in both the training and validation cohorts. Clinicopathological indicators associated with prognosis in the univariate and multivariate regression analyses were identified and added to the RPI to form the RCPI. The RCPI was also used to divide populations into different risk groups, and the high-risk group had poor OS (P < 0.001 and P < 0.001, respectively) and EFS (P < 0.05 and P < 0.05, respectively). Finally, the RCPI had higher accuracy than the RPI for the prediction of OS (60 month AUC values of 0.730 and 0.852, respectively) and EFS (60 month AUC values of 0.663 and 0.763, respectively) in both the training and validation cohorts. Moreover, these differentially expressed genes may be involved in certain NBL-related events. Conclusions: The RCPI could reliably categorize NBL patients based on different risks of death.
CRIS-Team WoS Importer:2020-01-03

Development of Admission to Radiotherapy Departments in Germany: A Population-Based Study of DRG Data - Medenwald, D.; Fietkau, Rainer; Klautke, G.; Wuerschmidt, F.; Vordermark, D. (STRAHLENTHERAPIE UND ONKOLOGIE, 2021)
CRIS-Team WoS Importer:2021-07-16

Development of a flow cytometry-based whole-blood prognostic immune signature in metastatic cancer patients treated with immune checkpoint inhibitors - Zhou, Jianguo; Donaubauer, Anna-Jasmina; Frey, Benjamin; Becker, Ina; Rutzner, Sandra; Eckstein, Markus; Sun, R.; Ma, H.; Schubert, Philipp; Schweizer, C.; Fietkau, Rainer; Deutsch, E.; et al. (ANNALS OF ONCOLOGY, 2020)
CRIS-Team WoS Importer:2021-01-15

Development of a Modular Assay for Detailed Immunophenotyping of Peripheral Human Whole Blood Samples by Multicolor Flow Cytometry - Rühle, Paul-Friedrich; Fietkau, Rainer; Gaipl, Udo; Frey, Benjamin (International Journal of Molecular Sciences, 2016)
The monitoring of immune cells gained great significance in prognosis and prediction of therapy responses. For analyzing blood samples, the multicolor flow cytometry has become the method of choice as it combines high specificity on single cell level with multiple parameters and high throughput. Here, we present a modular assay for the detailed immunophenotyping of blood (DIoB) that was optimized for an easy and direct application in whole blood samples. The DIoB assay characterizes 34 immune cell subsets that circulate the peripheral blood including all major immune cells such as T cells, B cells, natural killer (NK) cells, monocytes, dendritic cells (DCs), neutrophils, eosinophils, and basophils. In addition, it evaluates their functional state and a few non-leukocytes that also have been associated with the outcome of cancer therapy. This DIoB assay allows a longitudinal and close-meshed monitoring of a detailed immune status in patients requiring only 2.0 mL of peripheral blood and it is not restricted to peripheral blood mononuclear cells. It is currently applied for the immune monitoring of patients with glioblastoma multiforme (IMMO-GLIO-01 trial, NCT02022384), pancreatic cancer (CONKO-007 trial, NCT01827553), and head and neck cancer (DIREKHT trial, NCT02528955) and might pave the way for immune biomarker identification for prediction and prognosis of therapy outcome.
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Development of an immunological prognostic Signature in metastatic Patients who were treated with Immune Checkpoint Inhibitors as part of the ST-ICI Study - Zhou, Jianguo; Donaubauer, Anna-Jasmina; Frey, Benjamin; Becker, Ina; Rutzner, Sandra; Sun, R.; Ma, H.; Fietkau, Rainer; Deutsch, E.; Hecht, Markus; Gaipl, Udo (STRAHLENTHERAPIE UND ONKOLOGIE, 2020)
CRIS-Team WoS Importer:2020-10-02

Development of curative therapies for Ewing sarcomas by interdisciplinary cooperative groups in Europe - Boelling, T.; Braun-Munzinger, G.; Burdach, S.; Calaminus, G.; Craft, A.; Delattre, O.; Deley, M. -C. L.; Dirksen, U.; Dockhorn-Dworniczak, B.; Dunst, J.; Engel, S.; Faldum, Andreas; et al. (Klinische Pädiatrie, 2015)
Curative therapies for Ewing sarcoma have been developed within cooperative groups. Consecutive clinical trials have systematically assessed the impact and timing of local therapy and the activity of cytotoxic drugs and their combinations. They have led to an increase of long-term disease-free survival to around 70% in patients with localized disease. Translational research in ES remains an area in which interdisciplinary and international cooperation is essential for future progress. This article reviews current state-of-the art therapy, with a focus on trials performed in Europe, and summarizes novel strategies to further advance both the cure rates and quality of survival.
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Development of Recurrence and Long-term Toxicity in Prostate Carcinoma after combined Radiotherapy with interstitial Brachytherapy Boost - Schweizer, Claudia; Strnad, Vratislav; Fietkau, Rainer (STRAHLENTHERAPIE UND ONKOLOGIE, 2022)
CRIS-Team WoS Importer:2022-06-03

Diagnosis and Therapeutic Management in Kidney, Ureter and Bladder Trauma - Hirsch, Karin; Heinz, Marco; Wullich, Bernd (Aktuelle Urologie, 2017)
Trauma refers to the destruction of tissues or organs by external forces and it is the most common cause of mortality and morbidity in children (1, 2). Injuries of the genitourinary tract may be the result of blunt (falls, sport injuries, motor vehicle accidents and sexual abuse) or penetrating (stab wounds, gun shots, falling onto sharp objects) injuries. The genitourinary tract is significantly injured in 2.9 % of paediatric trauma patients [4]. In the paediatric population, the kidney is the most affected organ in the genitourinary tract (> 60 % of all genitourinary tract injuries) [4]. Blunt renal trauma is the most common type of injury representing 80-90 % [4]. The paediatric kidney is more susceptible due to less abdominal and retroperitoneal fat, weaker trunk and abdominal muscles and a lower position in the abdomen. Preexisting renal abnormalities such as UPJ obstruction, hydronephrosis, horseshoe kidney or ectopic kidney make the kidney more vulnerable. Spiral computed tomography is the gold standard method for radiological assessment. Surgical intervention is needed only in the minority of children. Isolated ureteral injury due to trauma is very rare in children. Penetrating ureteral trauma is more common than blunt trauma in the paediatric population. Among all urological trauma cases, the incidence of ureteral injury is lower than 1 % [4]. Ureteral injuries include contusion, laceration and avulsion. Because of their hyperextensible vertebral column, children are more likely to sustain deceleration injuries. Delayed films of IVP and CT are the main diagnostic tools whereas the gold standard is retrograde ureteropyelography. Ureteral injury treatment options depend on the location of injury. The bladder in children is a more abdominal organ than in adults. Lying in an exposed position above the pelvis, the bladder is more vulnerable in this age group as it is less well protected due to the less developed abdominal fat and rectus muscles. Here, too, the most common type of trauma is blunt injury. High percentages of bladder injuries are associated with pelvic fractures (70-90 %) [4]. The average rate of bladder injury in patients with pelvic fractures is 4 % in the paediatric age group [4]. Conventional or CT cystography is the gold standard method of imaging.
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Diagnosis of A3 Pulley Injuries Using Ultrasound. - Schoeffl, Isabelle; Deeg, Johannes; Lutter, Christoph; Bayer, Thomas; Schöffl, Volker (Sportverletzung-Sportschaden, 2018)
RATIONALE AND OBJECTIVES: Pulley ruptures are the most common injuries in sport climbing. Ruptures of the A2 and A4 pulleys have been studied extensively, and ultrasound has proven to be a highly sensitive and specific tool for their diagnosis. However, the correct diagnosis of A3 pulley ruptures continues to be a challenge. Therefore, we investigated a novel approach to this pathology. MATERIAL AND METHODS: Eighteen fingers from nine different human cadavers were examined using high-resolution, dynamic ultrasound before and after being subjected to different combinations of singular and multiple iatrogenic pulley ruptures in a standardised fashion. Special attention was paid to the behaviour of the volar plate (VP) with respect to the proximal interphalangeal joint (PIP) and the flexor tendons before and after pulley rupture. RESULTS: Injuries to the A2 and A4 pulleys were diagnosed via ultrasound with sensitivities of 90 % and 94 % and specificities of 100 % and 97 %, respectively. A direct visualisation of the A3 pulley was achieved in 61 % of the fingers. The VP became significantly thicker and shorter during finger flexion as well as after A3 pulley rupture. The distance between tendon and VP became significantly more pronounced after A3 pulley rupture. For distances greater than 0.9 mm between VP and tendon, a sensitivity of 76 % and a specificity of 94 % were achieved for determining A3 pulley ruptures. CONCLUSION: The distance measurement between VP and tendon was found to be a valid indirect method for the diagnosis of A3 pulley ruptures. This approach is the first ultrasound method for accurately diagnosing A3 pulley ruptures.
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Keywords: sport climbing; finger injury; volar plate; pulley

Diagnostic imaging of benign and malignant osseous tumors of the fingers - Melamud, Kira; Drape, Jean-Luc; Hayashi, Daichi; Roemer, Frank; Zentner, Joachim; Guermazi, Ali (Radiographics, 2014)
Primary lesions of the tubular bones of the digits are not uncommon, and the vast majority of these lesions are benign. Benign intramedullary lesions such as enchondromas are frequently discovered incidentally, unless they are associated with a pathologic fracture. Expansile lesions or lesions that are pedunculated and protrude from the cortex may manifest with pain and functional deficits from local inflammatory reactions. Systemic disorders such as sarcoidosis and local soft-tissue lesions with involvement of adjacent bone may mimic primary phalangeal bone tumors. Primary or secondary malignant lesions of the phalanges, most commonly chondrosarcomas, are extremely rare, and their characterization may require the use of multiple modalities, including radiography, computed tomography, and magnetic resonance imaging. Although ultrasonography is extremely useful in the evaluation of soft-tissue lesions of the hand, its role in the evaluation of osseous lesions is limited. The authors describe the imaging features of the most common benign osseous and chondral lesions of the fingers, including enchondromas, cystic lesions, and osteochondromas. In addition, they discuss malignant entities that may occur in the fingers (eg, chondrosarcomas and metastatic lesions) and commonly encountered mimics of primary osseous lesions (eg, glomus tumors, intraosseous epidermal inclusion cysts, infectious entities, and manifestations of systemic diseases). They also discuss the advantages and disadvantages of the most commonly used imaging modalities in differentiating benign from malignant lesions.
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Die Bedeutung der Strahlentherapie im Kontext immer effektiver werdender Systemtherapien beim metastasierten NSCLC – Hinweise aus einer Rezidivanalyse nach Immuncheckpointinhibitoren - Schubert, Philipp; Fietkau, Rainer; Hecht, Markus (Strahlentherapie und Onkologie, 2021)
CRIS-Team Scopus Importer:2021-12-03

Differences and Similarities in the Pattern of Early Metabolic and Morphologic Response after Induction Chemo-Immunotherapy versus Induction Chemotherapy Alone in Locally Advanced Squamous Cell Head and Neck Cancer - Beck, Michael; Semrau, Sabine; Haderlein, Marlen; Gostian, Antoniu-Oreste; Hartwich, Julius; Mueller, Sarina K.; Kallies, Annett; Geppert, Carol-Immanuel; Schonath, Miriam; Putz, Florian; Gaipl, Udo; Frey, Benjamin; et al. (Cancers, 2022)
Simple Summary There are differences and similarities when assessing the short-term therapeutic response of chemotherapy and chemotherapy plus immunotherapy using imaging techniques, which may be necessary to make treatment decisions in malignant head and neck tumors. After both chemo- and immunochemotherapy, remission becomes measurable in cross-sectional and metabolic diagnostics after only one cycle of therapy, with (18)FDG-PET/CT predicting complete remission of tumor cells in a representative biopsy better than MRI/CT examination in both therapeutic modalities. While complete tumor remission is highly likely (88%) after immunochemotherapy in tumors with low residual activity (<= 40% of initial SUV), this is less common after chemotherapy alone (65%). In metabolic nonresponse with more than 80% residual activity, the probability of complete remission nevertheless is low after chemotherapy alone (6%). After immunochemotherapy, these false nonresponders are common (35%), requiring additional diagnostics by deep biopsy. Cases of pseudoprogression with an increase of SUVmax of more than 125% of the baseline were not observed. Background: In head and neck cancer patients, parameters of metabolic and morphologic response of the tumor to single-cycle induction chemotherapy (IC) with docetaxel, cis- or carboplatin are used to decide the further course of treatment. This study investigated the effect of adding a double immune checkpoint blockade (DICB) of tremelimumab and durvalumab to IC on imaging parameters and their significance with regard to tumor cell remission. Methods: Response variables of 53 patients treated with IC+DICB (ICIT) were compared with those of 104 who received IC alone. Three weeks after one cycle, pathologic and, in some cases, clinical and endoscopic primary tumor responses were evaluated and correlated with a change in 18F-FDG PET and CT/MRI-based maximum-standardized uptake values (SUVmax) before (SUV(max)pre), after treatment (SUV(max)post) and residually (resSUV(max) in % of SUV(max)pre), and in maximum tumor diameter (D-max) before (D(max)pre) and after treatment (D(max)post) and residually (resD). Results: Reduction of SUVmax and D-max occurred in both groups; values were SUV(max)pre: 14.4, SUV(max)post: 6.6, D(max)pre: 30 mm and D(max)post: 23 mm for ICIT versus SUV(max)pre: 16.5, SUV(max)post: 6.4, D(max)pre: 21 mm, and D(max)post: 16 mm for IC alone (all p < 0.05). ResSUV(max) was the best predictor of complete response (IC: AUC: 0.77; ICIT: AUC: 0.76). Metabolic responders with resSUV(max) <= 40% tended to have a higher rate of CR to ICIT (88%; n = 15/17) than to IC (65%; n = 30/46; p = 0.11). Of the metabolic nonresponders (resSUV(max) > 80%), 33% (n = 5/15) achieved a clinical CR to ICIT versus 6% (n = 1/15) to IC (p = 0.01). Conclusions: ICIT and IC quickly induce a response and 18F-FDG PET is the more accurate modality for identifying complete remission. The rate of discrepant response, i.e., pCR with metabolic nonresponse after ICIT was >30%.
CRIS-Team WoS Importer:2022-10-21

Differences in and Prognostic Value of Quality of Life Data in Rectal Cancer Patients with and without Distant Metastases - Frank, Fabian; Hecht, Markus; Loy, Florian; Rutzner, Sandra; Fietkau, Rainer; Distel, Luitpold (Healthcare, 2021)
(1) Background: Individualization of treatment is a major challenge in oncology and requires a variety of predictive and prognostic parameters. In addition to tumor biology analyses, baseline health-related quality of life might be a valid tool to predict overall survival. This study was conducted to evaluate the prognostic relevance of baseline quality of life data in patients with rectal cancer. In this context, differences between patients with and without distant metastases were of particular interest. (2) Methods: Our cohort included 258 patients with rectal cancer treated in the radiotherapy department of the University Hospital Erlangen. Patients completed the European Organisation for Research and Treatment of Cancer (EORTC) core quality of life questionnaire (QLQ C30) and colorectal cancer questionnaire (CR38). Clinical and survival data were provided by the Giessener Tumor Documentation System (GTDS) of the Comprehensive Cancer Center Erlangen-EMN (CCC, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany). Statistical analyses were performed using Kaplan-Meier analyses and univariate and multivariate Cox regression. (3) Results: A cohort of 258 patients with rectal adenocarcinoma was analyzed including 50 patients (19.4%) with metastatic disease. No differences were observed between patients with and without distant metastases in most areas of quality of life studied, with the exception of physical function, loss of appetite, chemotherapy side effects and weight loss. Gender, baseline physical function, sexual function, diarrhea, and weight loss over time had a prognostic value in the entire cohort. Appetite loss was an additional prognostic parameter in patients with distant metastases. (4) Conclusions: The quality of life of patients with metastatic disease differed only slightly from non-metastatic patients. Health-related quality of life data provide prognostic information for patients with rectal cancer.
CRIS-Team WoS Importer:2021-02-12

Differences in Dose Coverage and Uniformity in Fractionated High-Dose-Rate Interstitial Breast Brachytherapy Based on EMT Measurements - Kellermeier, Markus; Hofmann, B.; Strnad, Vratislav; Bert, Christoph (2016)
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Differences of the immune phenotype of breast cancer cells after ex vivo hyperthermia by warm-water or microwave radiation in a closed-loop system alone or in combination with radiotherapy - Hader, Michael; Savcigil, Deniz Pinar; Rosin, Andreas; Ponfick, Philipp; Gekle, Stephan; Wadepohl, Martin; Bekeschus, Sander; Fietkau, Rainer; Frey, Benjamin; Schlücker, Eberhard; Gaipl, Udo (Cancers, 2020)
The treatment of breast cancer by radiotherapy can be complemented by hyperthermia. Little is known about how the immune phenotype of tumor cells is changed thereby, also in terms of a dependence on the heating method. We developed a sterile closed-loop system, using either a warm-water bath or a microwave at 2.45 GHz to examine the impact of ex vivo hyperthermia on cell death, the release of HSP70, and the expression of immune checkpoint molecules (ICMs) on MCF-7 and MDA-MB-231 breast cancer cells by multicolor flow cytometry and ELISA. Heating was performed between 39 and 44◦C. Numerical process simulations identified temperature distributions. Additionally, irradiation with 2 × 5 Gy or 5 × 2 Gy was applied. We observed a release of HSP70 after hyperthermia at all examined temperatures and independently of the heating method, but microwave heating was more effective in cell killing, and microwave heating with and without radiotherapy increased subsequent HSP70 concentrations. Adding hyperthermia to radiotherapy, dynamically or individually, affected the expression of the ICM PD-L1, PD-L2, HVEM, ICOS-L, CD137-L, OX40-L, CD27-L, and EGFR on breast cancer cells. Well-characterized pre-clinical heating systems are mandatory to screen the immune phenotype of tumor cells in clinically relevant settings to define immune matrices for therapy adaption.
CRIS-Team Scopus Importer:2020-05-08
Keywords: Breast cancer; Danger signals; EGFR; Hyperthermia; Immune checkpoint molecules; Immunogenic cancer cell phenotype; Immunotherapy; Microwave-heating; Multimodal tumor therapies; Radiotherapy

Differentiation of ductal carcinoma in situ versus fibrocystic changes by magnetic resonance imaging: are there pathognomonic imaging features? - Dietzel, Matthias; Kaiser, Clemens G.; Wenkel, Evelyn; Clauser, Paola; Uder, Michael; Schulz-Wendtland, Rüdiger; Baltzer, Pascal A. T. (Acta Radiologica, 2017)
Background In breast magnetic resonance imaging (MRI), the diagnosis of ductal carcinoma in situ (DCIS) remains controversial; the most challenging cause of false-positive DCIS diagnosis is fibrocystic changes (FC). Purpose To search for typical and pathognomonic patterns of DCIS and FC using a standard clinical MRI protocol. Material and Methods Consecutive patients scheduled for breast MRI (standardized protocols @ 1.5T: dynamic-T1-GRE before/after Gd-DTPA [0.1 mmol/kg body weight (BW)]; T1-TSE), with subsequent pathological sampling, were investigated. Sixteen MRI descriptors were prospectively assessed by two experienced radiologists in consensus (blinded to pathology) and explored in patients with DCIS (n = 77) or FC (n = 219). Univariate and multivariate statistics were performed to identify the accuracy of descriptors (alone, combined). Furthermore, pathognomonic descriptor-combinations with an accuracy of 100% were explored (?(2) statistics; decision trees). Results Six breast MRI descriptors significantly differentiated DCIS from FC ( Pcorrected < 0.05; odds ratio < 7.9). Pathognomonic imaging features were present in 33.8% (n = 100) of all cases allowing the identification of 42.9% of FC (n = 94). Conclusion Pathognomonic patterns of DCIS and FC were frequently observed in a standard clinical MRI protocol. Such imaging patterns could decrease the false-positive rate of breast MRI and hence might help to decrease the number of unnecessary biopsies in this clinically challenging subgroup.
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Diffuse Encephalopathy Associated with Isolated Cerebral Langerhans Cell Histiocytosis - Rompel, Oliver; Buslei, Rolf; Hammon, Matthias; Dörr, Helmuth-Günther; Chada, Martin; Nikkhah, Guido; Uder, Michael; Trollmann, Regina (Pediatric Neurology, 2016)
Langerhans cell histiocytosis is a rare disease of the monocyte-macrophage system. Abnormalities of the hypothalamic-pituitary region are common in individuals with central nervous system involvement.This six-year-old boy developed rapidly progressive aggressive behavior, central diabetes insipidus, and repeated complex partial seizures. Magnetic resonance imaging revealed a diffuse leukoencephalopathy-like pattern and numerous infratentorial and supratentorial granulomatous nodules in the brain parenchyma along with infundibular and hypothalamic mass lesions. Stereotactic serial biopsies enabled histopathologic and immunohistochemical diagnosis of Langerhans cell histiocytosis.Similar MRI findings have rarely been described in the literature. These findings represent part of the broad neuroradiological spectrum of Langerhans cell histiocytosis of the nervous system in children.
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Diffusion-weighted MR imaging of benign and malignant breast lesions before and after contrast enhancement - Janka, Rolf Matthias; Hammon, Matthias; Geppert, C.; Nothhelfer, A.; Uder, Michael; Wenkel, Evelyn (Röfo-Fortschritte auf dem Gebiet der Röntgenstrahlen und der bildgebenden Verfahren, 2014)
Many publications describe the use of diffusion-weighted imaging (DWI) in breast MRI. This article addresses the question of when to apply the DWI sequence in the course of the scan protocol. The effect of T1-shortening contrast media (CM) on the ADC values of breast lesions is investigated.Data were acquired on a 1.5 T scanner. 60 patients with 79 lesions (20 benign, 59 malignant) were included. The DWI sequence (4 mm slice thickness, b-values: 50, 400, 800) was applied before and after CM administration. Before calculating the ADC map, the b50, b400 and b800 series were analyzed concerning lesion displacement. ADC values before and after CM application were compared.The mean lesion size was 1.5 ± 0.8 cm. On the basis of the b50 and b400 measurements, the mean ADC value of benign lesions was 1.89 ± 0.30 × 10-3 mm2/s before and 1.85 ± 0.28 ×10-3 mm2/s after CM administration. The consecutive values for two pure mucinous carcinomas were 1.88 × 10-3 mm2/s and 1.81 × 103 mm2/s and for the remaining malignant lesions 1.00 ± 0.18 × 10-3 mm2/s and 0.88 ± 0.21 × 10-3 mm2. On the basis of the b50, b400 and b800 measurements, the mean ADC value of benign lesions was 1.99 ± 0.37 × 10-3 mm2/s before and 1.97 ± 0.30 × 10-3 mm2/s after CM application, whereas the mean ADC value of the malignant lesions was 0.90 ± 0.14 × 10-3 mm2/s before and 0.80 ± 0.14 × 10-3 mm2/s after CM application. While there was no significant change for benign lesions, the ADC value decrease in post-contrast malignant lesions was highly significant.DWI after CM is possible and even leads to slightly better lesion discrimination between benign and malignant. However, further studies need to be performed to verify this. Citation Format: o?Janka R, Hammon M, Geppert C et al. Diffusion-Weighted MR Imaging of Benign and Malignant Breast Lesions Before and After Contrast Enhancement. Fortschr Röntgenstr 2014; 186: 130 - 135.
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Dissecting Tumor Antigens and Immune Subtypes of Glioma to Develop mRNA Vaccine - Zhong, Hua; Liu, Shuai; Cao, Fang; Zhao, Yi; Zhou, Jianguo; Tang, Feng; Peng, Zhaohua; Li, Yangsheng; Xu, Shen; Wang, Chunlin; Yang, Guohua; Li, Zhi Qiang (Frontiers in Immunology, 2021)
Background: Nowadays, researchers are leveraging the mRNA-based vaccine technology used to develop personalized immunotherapy for cancer. However, its application against glioma is still in its infancy. In this study, the applicable candidates were excavated for mRNA vaccine treatment in the perspective of immune regulation, and suitable glioma recipients with corresponding immune subtypes were further investigated. Methods: The RNA-seq data and clinical information of 702 and 325 patients were recruited from TCGA and CGGA, separately. The genetic alteration profile was visualized and compared by cBioPortal. Then, we explored prognostic outcomes and immune correlations of the selected antigens to validate their clinical relevance. The prognostic index was measured via GEPIA2, and infiltration of antigen-presenting cells (APCs) was calculated and visualized by TIMER. Based on immune-related gene expression, immune subtypes of glioma were identified using consensus clustering analysis. Moreover, the immune landscape was visualized by graph learning-based dimensionality reduction analysis. Results: Four glioma antigens, namely ANXA5, FKBP10, MSN, and PYGL, associated with superior prognoses and infiltration of APCs were selected. Three immune subtypes IS1–IS3 were identified, which fundamentally differed in molecular, cellular, and clinical signatures. Patients in subtypes IS2 and IS3 carried immunologically cold phenotypes, whereas those in IS1 carried immunologically hot phenotype. Particularly, patients in subtypes IS3 and IS2 demonstrated better outcomes than that in IS1. Expression profiles of immune checkpoints and immunogenic cell death (ICD) modulators showed a difference among IS1–IS3 tumors. Ultimately, the immune landscape of glioma elucidated considerable heterogeneity not only between individual patients but also within the same immune subtype. Conclusions: ANXA5, FKBP10, MSN, and PYGL are identified as potential antigens for anti-glioma mRNA vaccine production, specifically for patients in immune subtypes 2 and 3. In summary, this study may shed new light on the promising approaches of immunotherapy, such as devising mRNA vaccination tailored to applicable glioma recipients.
CRIS-Team Scopus Importer:2021-09-24
Keywords: glioma; immune landscape; immune subtypes; mRNA vaccine; tumor antigens

Distant metastases in colorectal carcinoma: A proposal for a new M1 subclassification - Merkel, Susanne; Weber, K.; Croner, R. S.; Golcher, H.; Göhl, Jonas; Agaimy, Abbas; Semrau, S.; Wein, Axel; Hohenberger, Werner; Wittekind, C.; Siebler, Jürgen (Ejso, 2016)
In 2010, the seventh Tumour-Node-Metastasis (TNM) cancer staging system of the International Union for Cancer Control (UICC) and the American Joint Committee of Cancer (AJCC) introduced a subdivision of M1 in the TNM classification of colorectal carcinomas. For the eighth TNM edition which will be released in the autumn of 2016 and will become effective in January 2017 new proposals are appreciated. The aim of our study was to define a new and better proposal for M1 subclassification.In a total of 814 patients with stage IV colorectal carcinoma treated between 1995 and 2013 prognostic factors were analysed in univariate and multivariate analyses.Advanced age, treatment in the earlier period 1995-2003, involvement of multiple metastatic sites, and non-curative resection were found to be independent prognostic factors. In patients with only one metastatic site, survival was good in patients with liver or lung metastasis, moderate in patients with metastasis of the peritoneum or non-regional lymph nodes and poor in patients with other rarely metastatic involved organs. The new proposal defines M1a, Metastasis confined to one organ: liver or lung (2-year survival 51.6%); M1b, Metastasis confined to one organ: peritoneum or non-regional lymph nodes, or Metastasis confined to liver plus lung (2-year survival 39.4%); and M1c, Metastasis confined to one organ: all other sites, or Metastasis in more than one organ, except liver plus lung (2-year survival 21.6%).The new proposal can identify three prognostic groups in stage IV colorectal carcinomas with significant differences in survival.
EVALuna2:2060

Distinct increased outliers among 136 rectal cancer patients assessed by ?H2AX - Kroeber, Jana; Wenger, Barbara; Schwegler, Manuela; Daniel, Christoph; Schmidt, Manfred; Djuzenova, Cholpon S.; Polat, Buelent; Flentje, Michael; Fietkau, Rainer; Distel, Luitpold (Radiation Oncology, 2015)
In recent years attention has focused on ?H2AX as a very sensitive double strand break indicator. It has been suggested that ?H2AX might be able to predict individual radiosensitivity. Our aim was to study the induction and repair of DNA double strand breaks labelled by ?H2AX in a large cohort.In a prospective study lymphocytes of 136 rectal cancer (RC) patients and 59 healthy individuals were ex vivo irradiated (IR) and initial DNA damage was compared to remaining DNA damage after 2 Gy and 24 hours repair time and preexisting DNA damage in unirradiated lymphocytes. Lymphocytes were immunostained with anti-?H2AX antibodies and microscopic images with an extended depth of field were acquired. ?H2AX foci counting was performed using a semi-automatic image analysis software.Distinct increased values of preexisting and remaining ?H2AX foci in the group of RC patients were found compared to the healthy individuals. Additionally there are clear differences within the groups and there are outliers in about 12% of the RC patients after ex vivo IR.The ?H2AX assay has the capability to identify a group of outliers which are most probably patients with increased radiosensitivity having the highest risk of suffering radiotherapy-related late sequelae.
EVALuna2:18245

Distinguishing Progression and Radionecrosis in large progressive Brain Metastases after Stereotaxy by integrating Radiomics, Dose Radiomics and clinical Risk Factors - Sommer, Phillip; Huang, Yixing; Srinivasan, Aishwarya Lakshmi; Fischer, Stefan; Dörfler, Arnd; Schmidt, Manuel; Frey, Benjamin; Maier, Andreas; Fietkau, Rainer; Bert, Christoph; Putz, Florian (STRAHLENTHERAPIE UND ONKOLOGIE, 2022)
CRIS-Team WoS Importer:2022-06-03

DNA as the main target in radiotherapy—a historical overview from first isolation to anti-tumour immune response - Frey, Benjamin; Borgmann, Kerstin; Jost, Tina; Greve, Burkhard; Oertel, Michael; Micke, Oliver; Eckert, Franziska (Strahlentherapie und Onkologie, 2023)
DNA damage is one of the foremost mechanisms of irradiation at the biological level. After the first isolation of DNA by Friedrich Miescher in the 19th century, the structure of DNA was described by Watson and Crick. Several Nobel Prizes have been awarded for DNA-related discoveries. This review aims to describe the historical perspective of DNA in radiation biology. Over the decades, DNA damage has been identified and quantified after irradiation. Depending on the type of sensing, different proteins are involved in sensing DNA damage and repairing the damage, if possible. For double-strand breaks, the main repair mechanisms are non-homologous end joining and homologous recombination. Additional mechanisms are the Fanconi anaemia pathway and base excision repair. Different methods have been developed for the detection of DNA double-strand breaks. Several drugs have been developed that interfere with different DNA repair mechanisms, e.g., PARP inhibitors. These drugs have been established in the standard treatment of different tumour entities and are being applied in several clinical trials in combination with radiotherapy. Over the past decades, it has become apparent that DNA damage mechanisms are also directly linked to the immune response in tumours. For example, cytosolic DNA fragments activate the innate immune system via the cGAS STING pathway.
CRIS-Team Scopus Importer:2023-09-01
Keywords: DNA double-strand breaks; DNA repair; History; Immunooncology; Radiobiology

Does a dedicated Radiation Planning MRI add Value to cranial Stereotaxy? - Mengling, Veit; Putz, Florian; Perrin, R.; Fietkau, Rainer; Bert, Christoph (STRAHLENTHERAPIE UND ONKOLOGIE, 2020)
CRIS-Team WoS Importer:2020-10-02

Does the Planning MRI for cranial Stereotaxy have to be performed in the Irradiation Position? An Examination of Brain Tissue Deformations between MR Imaging in diagnostic and Radiation Positions - Putz, Florian; Mengling, Veit; Masitho, Siti; Perrin, R.; Roesch, Johannes; Weissmann, T.; Bäuerle, Tobias; Fietkau, Rainer; Bert, Christoph (STRAHLENTHERAPIE UND ONKOLOGIE, 2020)
CRIS-Team WoS Importer:2020-10-02

Dose adjustment of cisplatin, etoposide, and ifosfamide according to kidney function: a retrospective analysis and implications for medication safety - Grafe, Carolin; Semrau, Sabine; Hein, Alexander; Beckmann, Matthias; Mackensen, Andreas; Dörje, Frank; Fromm, Martin (Naunyn-Schmiedeberg's Archives of Pharmacology, 2018)
Clearance of cisplatin, etoposide, and ifosfamide depends on kidney function and dosages should be adjusted in patients with renal impairment. However, there is still limited data on the adherence of physicians to dosing recommendations for these drugs in cancer patients with renal impairment. Three thousand four hundred forty-eight prescriptions to 369 patients, treated in the Comprehensive Cancer Center of a German university hospital, were retrospectively evaluated. The administered relative doses of cisplatin, etoposide, and ifosfamide were compared with relative doses recommended at the time of prescription according to the patients' creatinine clearance. Cisplatin is contraindicated according to two German summary of product characteristics (SmPC) in patients with a creatinine clearance < 60 mL/min. Nevertheless, 37 cisplatin prescriptions were made for this group of patients (i.e., 2.0% of all cisplatin prescriptions). According to one German SmPC (valid in the year of data analysis), etoposide dosage should be reduced in patients with a creatinine clearance from 15 to 50 mL/min, while it is contraindicated below 15 mL/min. Thirteen etoposide prescriptions were without dose reduction in patients with creatinine clearance from 15 to 50 mL/min (1.5% of all etoposide prescriptions); one patient received etoposide with creatinine clearance below 15 mL/min. In 8.9% of ifosfamide prescriptions, patients did not receive a reduced dose in spite of respective recommendations. Dosages of cisplatin, etoposide, and ifosfamide are not always adjusted as recommended in patients with renal impairment. Consistent international dosing recommendations (e.g., in SmPCs), preferentially included in clinical decision support systems, should be developed to tackle this problem.
EVALuna2:25784

Dose calculation and verification of the Vero gimbal tracking treatment delivery - Prasetio, Heru; Wölfelschneider, Jens; Ziegler, Marc; Serpa, M.; Witulla, Barbara; Bert, Christoph (Physics in Medicine and Biology, 2018)
The Vero linear accelerator delivers dynamic tumor tracking (DTT) treatment using a gimbal motion. However, the availability of treatment planning systems (TPS) to simulate DTT is limited. This study aims to implement and verify the gimbal tracking beam geometry in the dose calculation. Gimbal tracking was implemented by rotating the reference CT outside the TPS according to the ring, gantry, and gimbal tracking position obtained from the tracking log file. The dose was calculated using these rotated CTs. The geometric accuracy was verified by comparing calculated and measured film response using a ball bearing phantom. The dose was verified by comparing calculated 2D dose distributions and film measurements in a ball bearing and a homogeneous phantom using a gamma criterion of 2%/2 mm. The effect of implementing the gimbal tracking beam geometry in a 3D patient data dose calculation was evaluated using dose volume histograms (DVH). Geometrically, the gimbal tracking implementation accuracy was <0.94 mm. The isodose lines agreed with the film measurement. The largest dose difference of 9.4% was observed at maximum tilt positions with an isocenter and target separation of 17.51 mm. Dosimetrically, gamma passing rates were >98.4%. The introduction of the gimbal tracking beam geometry in the dose calculation shifted the DVH curves by 0.05%-1.26% for the phantom geometry and by 5.59% for the patient CT dataset. This study successfully demonstrates a method to incorporate the gimbal tracking beam geometry into dose calculations. By combining CT rotation and MU distribution according to the log file, the TPS was able to simulate the Vero tracking treatment dose delivery. The DVH analysis from the gimbal tracking dose calculation revealed changes in the dose distribution during gimbal DTT that are not visible with static dose calculations.
EVALuna2:33026

Dose-dependent deterioration of swallowing function after induction chemotherapy and definitive chemoradiotherapy for laryngopharyngeal cancer - Haderlein, Marlen; Semrau, S.; Ott, O.; Speer, S.; Bohr, Christopher; Fietkau, Rainer (Strahlentherapie und Onkologie, 2014)
To evaluate the influence of clinical, treatment- and dose-dependent factors on posttreatment swallowing function after induction chemotherapy and definitive chemoradiotherapy in a group of homogeneously treated laryngopharyngeal cancer patients.From 28 May 2008 to 15 February 2013, 45 patients with borderline inoperable laryngopharyngeal cancer that had responded well to induction chemotherapy were treated with definitive chemoradiotherapy. Median follow-up was 22 months. Swallowing function and clinical data were prospectively analyzed using the EORTC QLQ-C30 questionnaire. Swallowing structures were retrospectively delineated on the original treatment planning CT. Dose-volume histograms were calculated for swallowing structures and Dmean, Dmax and V50-V64 values (in 2 Gy increments) were determined for each patient. Tumor volume and infiltration of the swallowing apparatus was defined by CT before induction chemotherapy.Of the 45 patients, 26 (57.8 %) fully regained swallowing function after chemoradiotherapy. A further 12 patients (26.7 %) were able to manage soft, pureed and/or liquid foods; the remaining 7 (15.6 %) were completely dependent on percutaneous endoscopic gastrostomy (PEG). Posttreatment swallowing function was significantly influenced by Dmean to the superior pharyngeal constrictor muscle (PCM, p = 0.041). Correlations between late dysphagia and dose-volume relationships in the superior PCM and soft palate were also observed, which were significant from V60 (p = 0.043) and V58 for the soft palate and superior PCM, respectively. Of the evaluated clinical and tumor-related factors, only alcohol abuse (p = 0.024) had an influence on posttreatment swallowing function.Almost 50 % of patients had deterioration of swallowing function after definitive chemoradiotherapy for laryngopharyngeal cancer. The dose to anatomical structures responsible for swallowing function appears to play a role. Therefore, in selected patients, target volume delineation for radiotherapy of laryngopharyngeal cancer should be optimized on an individual basis to spare the swallowing apparatus.
EVALuna2:18123

Dose-escalated re-irradiation improves outcome in locally recurrent head and neck cancer – Results of a large multicenter analysis - Roesch, Johannes; Oertel, Michael; Wegen, Simone; Trommer, Maike; Schleifenbaum, Julia; Hering, Dominik; Mäurer, Matthias; Knippen, Stefan; Dobiasch, Sophie; Waltenberger, Maria; von der Grün, Jens; Medenwald, Daniel; et al. (Radiotherapy and Oncology, 2023)
To determine efficacy and prognostic parameters of definitive re-irradiation of locoregionally recurrent squamous cell carcinoma of the head and neck (HNSCC). Materials and methods: Patients with locoregionally recurrent or second primary HNSCC undergoing re-irradiation with modern radiotherapy technique were eligible for this multicentric retrospective analysis. Main endpoints were overall survival (OS), progression-free survival (PFS) and locoregional control (LC). Univariate analyses were performed using the Kaplan Meier Method (log-rank). For multivariable analysis, Cox regression was used. Results: A total of 253 patients treated between 2009 and 2020 at 16 university hospitals in Germany were included. The median follow up was 27.4 months (range 0.5–130). The median OS and PFS were 13.2 (CI: 10.7 – 15.7) months and 7.9 (CI: 6.7 – 9.1) months, respectively, corresponding to two-year OS and PFS rates of 29 % and 19 %. Rates of locoregional progression and “in-field-failure” were 62 % and 51 % after two years. Multivariable Cox regression analysis identified good ECOG performance status and high radiation dose as independent prognostic parameters for OS. Doses above 50 Gy (EQD2) achieved longer median OS of 17.8 months (vs 11.7 months, p < 0.01) and longer PFS of 9.6 months (vs 6.8 months, p < 0.01). In addition, there was a trend for worse survival in patients with tracheostomy (multivariable, p = 0.061). Concomitant systemic therapy did not significantly impact PFS or OS. Conclusion: Re-irradiation of locally recurrent or second primary HNSCC is efficient, especially if doses above 50 Gy (EQD2) are delivered. ECOG performance score was the strongest prognostic parameter for OS and PFS.
CRIS-Team Scopus Importer:2023-02-17
Keywords: Head and neck cancer; HNSCC; Re-irradiation; Re-Radiochemotherapy; Recurrent; Reirradiation

Dose reduction in computed tomography of the chest: image quality of iterative reconstructions at a 50% radiation dose compared to filtered back projection at a 100% radiation dose - May, Matthias; Eller, A.; Stahl, Christian; Wuest, W.; Scharf, M.; Hammon, Matthias; Dankerl, P.; Schlechtweg, Philipp; Allmendinger, T.; Sedlmair, M.; Schmidt, B.; Uder, Michael; et al. (Röfo-Fortschritte auf dem Gebiet der Röntgenstrahlen und der bildgebenden Verfahren, 2014)
The aim of this study was to evaluate the potential of iterative reconstruction (IR) in chest computed tomography (CT) to reduce radiation exposure. The qualitative and quantitative image quality of standard reconstructions with filtered back projection (FBP) and half dose (HD) chest CT data reconstructed with FBP and IR was assessed.52 consecutive patients underwent contrast-enhanced chest CT on a dual-source CT system at 120 kV and automatic exposure control. The tube current was equally split on both tube detector systems. For the HD datasets, only data from one tube detector system was utilized. Thus, FD and HD data was available for each patient with a single scan. Three datasets were reconstructed from the raw data: standard full dose (FD) images applying FBP which served as a reference, HD images applying FBP and IR. Objective image quality analysis was performed by measuring the image noise in tissue and air. The subjective image quality was evaluated by 2 radiologists according to European guidelines. Additional assessment of artifacts, lesion conspicuity and edge sharpness was performed.Image noise did not differ significantly between HD-IR and FD-FBP (p = 0.254) but increased substantially in HD-FBP (p < 0.001). No statistically significant differences were found for the reproduction of anatomical and pathological structures between HD-IR and FD-FBP, subsegmental bronchi and bronchioli. The image quality of HD-FBP was rated inferior because of increased noise.A 50 % dose reduction in contrast-enhanced chest CT is feasible without a loss of diagnostic confidence if IR is used for image data reconstruction. Iterative reconstruction is another powerful tool to reduce radiation exposure and can be combined with other dose-saving techniques.o?Iterative reconstructions allow for image noise and artifact reduction.o?Comparable image data can thus be attained even at 50 % radiation dose.o?Diagnostic confidence remains unaffected.
EVALuna2:14376

Dose Reduction in the Swallowing Area by De-intensification of Radiotherapy in Patients with Head and Neck Cancer in the postoperative Situation - first Plan Analyzes of the DIREKHT Study - Haderlein, Marlen; Speer, Stefan; Hecht, Markus; Merten, Ricarda; Scherl, C.; Semrau, S.; Ott, O.; Fietkau, Rainer (2018)
EVALuna2:36499

Dose reduction to the swallowing apparatus and the salivary glands by de-intensification of postoperative radiotherapy in patients with head and neck cancer: First (treatment planning) results of the prospective multicenter DIREKHT trial - Haderlein, Marlen; Speer, Stefan; Ott, Oliver; Lettmaier, Sebastian; Hecht, Markus; Semrau, Sabine; Frey, Benjamin; Scherl, Claudia; Iro, Heinrich; Kesting, Marco Rainer; Fietkau, Rainer (Cancers, 2020)
Aim: Evaluating radiotherapy treatment plans of the prospective DIREKHT trial (ClinicalTrials.gov, NCT02528955) investigating de-intensification of radiotherapy in patients with head and neck cancer. Patients and Methods: The first 30 patients from the DIREKHT trial of the leading study centre were included in this analysis. Standard treatment plans and study treatment plans derived from the protocol were calculated for each patient. Sizes of planning target volumes (PTVs) and mean doses to organs at risk were compared using the Student’s t-test with paired samples. Results: Mean PTV3 including primary tumor region and ipsilateral elective neck up to a dose of 50 Gy in the study treatment plans was 662 mL (+/− 165 mL standard deviation (SD)) and therefore significantly smaller than those of the standard treatment plans (1166 mL (+/− 266 mL SD). In the medial and inferior constrictor muscles, cricopharyngeal muscle, glottic and supraglottic laryngeal areas, arytenoid cartilages, contralateral major salivary glands highly significant dose reductions (p < 0.0001) of more than 10 Gy were achieved in study treatment plan compared to standard treatment plan. Conclusion: De-intensification of radiotherapy led to smaller planning target volumes and clinical relevant dose reductions in the swallowing apparatus and in the contralateral salivary glands.
CRIS-Team Scopus Importer:2020-03-06
Keywords: De-intensification; Head neck cancer; Ipsilateral elective neck irradiation only; Postoperative; Radiotherapy; Salivary glands; Swallowing apparatus

Dose volume histogram constraints in patients with soft tissue sarcomas of the extremities and the superficial trunk treated with surgery and perioperative HDR brachytherapy: Dose Volume Histogram Constraints for Sarcoma Brachytherapy - Gómez-Álvarez, Jorge; Martín Pastor, Santiago; Gimeno, Marta; Lamo-Espinosa, José; Ramos, Luis I.; Cambeiro, Mauricio; Tagliaferri, Luca; Kovacs, Gyoergy; Strnad, Vratislav; San-Julián, Mikel; Martinez-Monge, Rafael (Radiotherapy and Oncology, 2022)
Background: Wound healing complications (WHC), osteoradionecrosis (ORN), and nerve damage (ND) are common adverse effects in adult patients with soft tissue sarcomas of the extremities and the superficial trunk treated with surgery and perioperative high dose rate brachytherapy (PHDRB) alone or combined with external beam radiotherapy (EBRT). Rationale: Analysis of the treatment factors contributing to these complications can potentially minimize their occurrence and severity. Patients: A total of 169 patients enrolled in two parallel prospective studies were included in this analysis. Previously Unirradiated cases (Group 1; n = 139) were treated with surgical resection, 16–24 Gy of PHDRB and 45 Gy of EBRT. Adjuvant chemotherapy was given to selected patients with high-grade tumors. Previously irradiated cases (Group 2; n = 30) were treated with surgical resection and 32–40 Gy of PHDRB without further EBRT. Methods: Patient factors, tumor factors, surgical factors, PHDRB factors and EBRT factors were analyzed using Cox univariate and multivariate analysis. Results: In Previously Unirradiated cases, WHC, ORN and ND occurred in 38.8%, 5.0% and 19.4%. Multivariate analysis indicated that WHC increased with CTV size (p = 0.02) and CTV2cm3 Physical dose (p = 0.02). ORN increased with Bone2cm3 EQD2 ≥ 67 Gy (p = 0.01) and ND was more frequent in patients with TV100 DVH-based dose (tissue volume encompassed by the 100% isodose) ≥ 84 Gy (p < 0.01). In Previously Irradiated cases, WHC, ORN and ND occurred in 63.3%, 3.3% and 23.3%. Multivariate analysis showed that WHC was more frequent in patients with Skin2cm3 Lifetime EQD2 ≥ 84 Gy (p = 0.01) and ND was more frequent after CTVD90 Physical Doses ≥ 40 Gy (p < 0.01). Conclusions: WHC in Previously Unirradiated patients can be minimized by using a more conservative CTV definition together with a meticulous implant technique and planning aimed to minimize hyperdose CTV2cm3 areas. In Previously Irradiated patients WHC may be mimimized considering Lifetime EQD2 Skin2cm3 doses. ORN can be reduced by using the Bone2cm3 EQD2 constraint. ND occurs more frequently in patients with large tumors receiving high treated volume doses, but no specific constraints can be recommended due to the lack of peripheral nerve definition during brachytherapy planning.
CRIS-Team Scopus Importer:2022-05-06
Keywords: Brachytherapy; External Beam Radiation Therapy; High Dose Rate; Late complications; Perioperative; Soft tissue sarcomas

Dosimetric evaluation of 6-DOF intra-fraction motion for SGRT of breast cancer patients - Sauer, Tim-Oliver; Ott, O.; Bert, Christoph (RADIOTHERAPY AND ONCOLOGY, 2022)
CRIS-Team WoS Importer:2022-07-08

Dosimetry, Optimization and FMEA of Total Skin Electron Irradiation (TSEI) - Shariff, Maya; Stillkrieg, Willi; Lotter, Michael; Lohmann, Daniel; Weissmann, Thomas; Fietkau, Rainer; Bert, Christoph (Zeitschrift für Medizinische Physik, 2022)
Purpose: Total Skin Electron Irradiation (TSEI) is a method for treating malignant cutaneous T-cell lymphomas. This work aims to implement and optimize the total skin technique established at Strahlenklinik Erlangen, Germany on two new linear accelerators and to quantify the risks using failure mode and effects (FMEA) analysis. Material and methods: TSEI is performed at a VersaHD accelerator (Elekta, Stockholm) with 6 MeV in the “high dose rate mode” HDRE and a nominal field size of 40 × 40 cm2. To reach the entire skin surface, the patients perform 6 different body positions at a distance of 330 cm behind an acrylic scatter plate, with two overlapping irradiation fields being radiated at 2 gantry angles per position. The irradiation technique was commissioned according to the recommendation of AAPM report 23. With the help of a reference profile at 270°, 2 gantry angles were calculated, which in total resulted in an optimal dose distribution. This was metrologically verified with ion-chamber measurements in the patient's longitudinal axis. The influence of the shape of the acrylic scatter plate and the distance between the acrylic scatter plate and patient was determined by measurements. The dose homogeneity was verified using an anthropomorphic disc phantom equipped with GafChromic films. The workflows and failure modes of the total skin technique were described in a process map and subsequently quantified with a FMEA analysis. Results: An optimal dose distribution is achieved at a distance of SSD = 330 cm, using the gantry angles 289° and 251°. The previously used segmented acrylic scatter plate was replaced by a flat plate (200 × 120 × 0.5 cm3), which is placed at a distance of 50 cm in front of the patient. The densitometric evaluation of the GafChromic films in the anthropomorphic disc phantom revealed an expected dose distribution of 3 Gy at a depth of up to 1.5 cm below the skin surface, with a homogeneity of ±10% over the phantom's longitudinal axis. By FMEA a maximum risk priority number of 30 was determined. Conclusion: Based on the calculations and measurements performed on the new accelerators as well as the risk analysis, we concluded that total skin therapy can be implemented clinically.
CRIS-Team Scopus Importer:2022-06-17
Keywords: Dosimetry; FMEA; HDRE; Mycosis fungoides; Quality assurance; Total Skin Electron Irradiation (TSEI)

Downstage migration after neoadjuvant chemoradiotherapy for rectal cancer: the reverse of the Will Rogers phenomenon? - Fokas, Emmanouil; Liersch, Torsten; Fietkau, Rainer; Hohenberger, Werner; Hess, Clemens; Becker, Heinz; Sauer, Rolf; Wittekind, Christian; Roedel, Claus (Cancer, 2015)
Downstaging after neoadjuvant treatment is increasingly used as a prognostic factor and surrogate endpoint in clinical trials. However, in recent trials of neoadjuvant 5-fluorouracil-based chemoradiotherapy for rectal cancer, downstaging did not translate into a benefit with regard to either disease-free survival (DFS) or overall survival. By analyzing the 10-year outcome data of the German CAO/ARO/AIO-94 phase 3 trial, the authors demonstrated that significantly fewer patients had poor prognostic features (eg, ypT3-4, ypN1-2) after preoperative 5-fluorouracil-based chemoradiotherapy. Nevertheless, these patients with International Union for Cancer Control stage II disease were found to be at a higher risk of developing distant metastases and had poorer DFS compared with patients with corresponding TNM tumor (sub)groups in the postoperative treatment arm, whereas patients with International Union for Cancer Control stage III disease demonstrated a nonsignificant trend toward a worse outcome after preoperative treatment. Overall, DFS remained identical in both treatment arms. Thus, "downstage migration" after neoadjuvant treatment resembles the reverse of the Will Rogers phenomenon and therefore may not be a reliable endpoint for long-term outcomes.
EVALuna2:15194

Drug priming enhances radiosensitivity of adamantinomatous craniopharyngioma via downregulation of survivin - Stache, Christina; Bils, Christiane; Fahlbusch, Rudolf; Flitsch, Joerg; Buchfelder, Michael; Stefanits, Harald; Czech, Thomas; Gaipl, Udo; Frey, Benjamin; Buslei, Rolf; Hoelsken, Annett (Neurosurgical Focus, 2016)
OBJECTIVE In this study, the authors investigated the underlying mechanisms responsible for high tumor recurrence rates of adamantinomatous craniopharyngioma (ACP) after radiotherapy and developed new targeted treatment protocols to minimize recurrence. ACPs are characterized by the activation of the receptor tyrosine kinase epidermal growth factor receptor (EGFR), known to mediate radioresistance in various tumor entities. The impact of tyrosine kinase inhibitors (TKIs) gefitinib or CUDC-101 on radiation-induced cell death and associated regulation of survivin gene expression was evaluated. METHODS The hypothesis that activated EGFR promotes radioresistance in ACP was investigated in vitro using human primary cell cultures of ACP (n = 10). The effects of radiation (12 Gy) and combined radiochemotherapy on radiosensitivity were assessed via cell death analysis using flow cytometry. Changes in target gene expression were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). Survivin, identified in qRT-PCR to be involved in radioresistance of ACP, was manipulated by small interfering RNA (siRNA), followed by proliferation and vitality assays to further clarify its role in ACP biology. Immunohistochemically, survivin expression was assessed in patient tumors used for primary cell cultures. RESULTS In primary human ACP cultures, activation of EGFR resulted in significantly reduced cell death levels after radiotherapy. Treatment with TKIs alone and in combination with radiotherapy increased cell death response remarkably, assessed by flow cytometry. CUDC-101 was significantly more effective than gefitinib. The authors identified regulation of survivin expression after therapeutic intervention as the underlying molecular mechanism of radioresistance in ACP. EGFR activation promoting ACP cell survival and proliferation in vitro is consistent with enhanced survivin gene expression shown by qRT-PCR. TKI treatment, as well as the combination with radiotherapy, reduced survivin levels in vitro. Accordingly, ACP showed reduced cell viability and proliferation after survivin downregulation by siRNA. CONCLUSIONS These results indicate an impact of EGFR signaling on radioresistance in ACP. Inhibition of EGFR activity by means of TKI treatment acts as a radiosensitizer on ACP tumor cells, leading to increased cell death. Additionally, the results emphasize the antiapoptotic and pro-proliferative role of survivin in ACP biology and its regulation by EGFR signaling. The suppression of survivin by treatment with TKI and combined radiotherapy represents a new promising treatment strategy that will be further assessed in in vivo models of ACP.
EVALuna2:7353

Dual mtor/dna-pk inhibitor cc-115 induces cell death in melanoma cells and has radiosensitizing potential - Bürkel, Felix; Jost, Tina; Hecht, Markus; Heinzerling, Lucie; Fietkau, Rainer; Distel, Luitpold (International Journal of Molecular Sciences, 2020)
CC-115 is a dual inhibitor of the mechanistic target of rapamycin (mTOR) kinase and the DNA-dependent protein kinase (DNA-PK) that is currently being studied in phase I/II clinical trials. DNA-PK is essential for the repair of DNA-double strand breaks (DSB). Radiotherapy is frequently used in the palliative treatment of metastatic melanoma patients and induces DSBs. Melanoma cell lines and healthy-donor skin fibroblast cell lines were treated with CC-115 and ionizing irradiation (IR). Apoptosis, necrosis, and cell cycle distribution were analyzed. Colony forming assays were conducted to study radiosensitizing effects. Immunofluorescence microscopy was performed to determine the activity of homologous recombination (HR). In most of the malign cell lines, an increasing concentration of CC-115 resulted in increased cell death. Furthermore, strong cytotoxic effects were only observed in malignant cell lines. Regarding clonogenicity, all cell lines displayed decreased survival fractions during combined inhibitor and IR treatment and supra-additive effects of the combination were observable in 5 out of 9 melanoma cell lines. CC-115 showed radiosensitizing potential in 7 out of 9 melanoma cell lines, but not in healthy skin fibroblasts. Based on our data CC-115 treatment could be a promising approach for patients with metastatic melanoma, particularly in the combination with radiotherapy.
CRIS-Team Scopus Importer:2020-12-25
Keywords: DNA repair; DNA-PK; Homologous recombination (HR); Kinase inhibitor; Melanoma; MTOR; Non-homologous end-joining (NHEJ); Radiosensitivity

Durvalumab improves prognosis of stage III non-small-cell lung cancer after definitive chemoradiotherapy - Hecht, Markus; Gaipl, Udo; Fietkau, Rainer (Strahlentherapie und Onkologie, 2018)
EVALuna2:33776

EARLY BLOOD CELL COUNT TEST (BCT) FOR SURVIVAL PREDICTION FOR NON-SMALL CELL LUNG CANCER PATIENTS TREATED WITH ATEZOLIZUMAB: INTEGRATED ANALYSIS OF 4 MULTICENTER CLINICAL TRIALS - Zhou, Jian-Guo; Wong, Ada Hang-Heng; Wang, Haitao; Jin, Su-Han; Tan, Fangya; Chen, Yu-Zhong; He, Si-Si; Shen, Gang; Frey, Benjamin; Fietkau, Rainer; Hecht, Markus; Shen, Bo; et al. (JOURNAL FOR IMMUNOTHERAPY OF CANCER, 2021)
Immune checkpoint inhibitor (ICI) therapy is a major breakthrough for non-small cell lung cancer (NSCLC) treatment given its high efficacy and tolerable toxicity. Although pre-treatment PD-L1 expression levels and tumor mutation burden (TMB) may serve as prognostic biomarkers for patient stratification, effective predictive biomarkers are lacking. Blood cell count test (BCT) is a routine, regular blood test conducted before and during treatment to provide a direct overview of the immune landscape based on the counts of various types of immune cells (ICs). For instance, previous studies showed that neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) both indicate poor treatment outcomes of ICI therapy of NSCLC patients.<br
CRIS-Team WoS Importer:2022-04-15

Early Mortality of Brain Cancer Patients and its Connection to Cytomegalovirus Reactivation During Radiochemotherapy - Goerig, Nicole; Frey, Benjamin; Korn, Klaus; Fleckenstein, Bernhard; Überla, Klaus; Schmidt, Manuel; Dörfler, Arnd; Engelhorn, Tobias; Eyüpoglu, Ilker Yasin; Rühle, Paul-Friedrich; Putz, Florian; Semrau, Sabine; et al. (Clinical Cancer Research, 2020)
PURPOSE: If routine diagnostics are inconclusive, neurologic deterioration and death of patients with brain cancer are attributed to tumor or therapy. Therefore, diagnosing symptoms of encephalopathy caused by human cytomegalovirus (HCMV) reactivation remains uncommon. We investigated the role of HCMV reactivation in neurologic decline and clinical outcome after the start of radiochemotherapy. EXPERIMENTAL DESIGN: HCMV analyses and extended MRI studies including additional independent retrospective neuroradiologic evaluation were performed at predetermined intervals and in case of sudden neurologic decline for 118 adult patients: 63 histologically proven high-grade gliomas, 55 with brain metastases. Immunophenotyping from simultaneously taken whole-blood samples was carried out to detect immune cells serving as prognostic marker for HCMV-associated complications. Symptomatic viremia and overall survival (OS) were the endpoints. RESULTS: Twenty-four percent (28/118) of all patients (12/44 glioblastoma, 3/13 anaplastic astrocytoma; 8/31 non-small cell lung cancer (NSCLC), 13/24 other brain metastases) developed HCMV-viremia during or within 4 weeks after radiotherapy; 21 of 28 patients experienced concurrent major neurologic decline, reversible by antiviral treatment. Identified by immunophenotyping, pretherapeutically low basophil counts predicted a high-risk for HCMV-associated encephalopathy (glioblastoma: P = 0.002, NSCLC: P = 0.02). Median OS was substantially reduced after HCMV-associated encephalopathy without MRI signs of tumor progression [glioblastoma: 99 vs. 570 days (calculated 1-year OS: 22% vs. 69%; P = 0.01) and NSCLC: 47 vs. 219 days (calculated 1-year OS: 0% vs. 32%; P = 0.02)]. CONCLUSIONS: For patients with brain cancer, HCMV reactivation after the start of radiochemotherapy is a frequent risk for cognitively detrimental but treatable encephalopathy and premature death. Routinely performed HCMV diagnostics, assessing basophil counts and study-based anti-viral regimens, are necessary to combat this hidden threat.See related commentary by Lawler et al., p. 3077.
CRIS-Team Scopus Importer:2020-07-17

ECG-based 4D-dose reconstruction of cardiac arrhythmia ablation with carbon ion beams: application in a porcine model - Richter, Daniel; Lehmann, H. Immo; Eichhorn, Anna; Constantinescu, Anna M.; Kaderka, Robert; Prall, Matthias; Lugenbiel, Patrick; Takami, Mitsuru; Thomas, Dierk; Bert, Christoph; Durante, Marco; Packer, Douglas L.; et al. (Physics in Medicine and Biology, 2017)
Noninvasive ablation of cardiac arrhythmia by scanned particle radiotherapy is highly promising, but especially challenging due to cardiac and respiratory motion. Irradiations for catheter-free ablation in intact pigs were carried out at the GSI Helmholtz Center in Darmstadt using scanned carbon ions. Here, we present real-time electrocardiogram (ECG) data to estimate time-resolved (4D) delivered dose. For 11 animals, surface ECGs and temporal structure of beam delivery were acquired during irradiation. R waves were automatically detected from surface ECGs. Pre-treatment ECG-triggered 4D-CT phases were synchronized to the R-R interval. 4D-dose calculation was performed using GSI's in-house 4D treatment planning system. Resulting dose distributions were assessed with respect to coverage (D95 and V95), heterogeneity (HI = D5-D95) and normal tissue exposure. Final results shown here were performed offline, but first calculations were started shortly after irradiation The D95 for TV and PTV was above 95% for 10 and 8 out of 11 animals, respectively. HI was reduced for PTV versus TV volumes, especially for some of the animals targeted at the atrioventricular junction, indicating residual interplay effects due to cardiac motion. Risk structure exposure was comparable to static and 4D treatment planning simulations. ECG-based 4D-dose reconstruction is technically feasible in a patient treatment-like setting. Further development of the presented approach, such as real-time dose calculation, may contribute to safe, successful treatments using scanned ion beams for cardiac arrhythmia ablation.
EVALuna2:36481

Editorial: Community series in immunotherapy with checkpoint inhibitors for non-small cell lung cancer, colon cancer, and esophageal cancer, volume II - Li, Yueyi; Wang, Yusha; Gao, Jinsheng; Tan, Keqin; Frey, Benjamin; Gaipl, Udo; Shi, Hubing; Ma, Xuelei (Frontiers in Immunology, 2023)
CRIS-Team Scopus Importer:2023-07-28
Keywords: colorectal cancer; editorial; esophageal cancer (EC); mmune checkpoint inhibitors (ICIs); non-small cell lung cancer (NSCLC)

Editorial: Immune-Related Adverse Events for Patients With Lung Cancer - Yang, Ruoning; Wang, Haiyang; Yin, Xiaomeng; Frey, Benjamin; Gaipl, Udo; Shi, Hubing; Ma, Xuelei (Frontiers in Oncology, 2022)
CRIS-Team WoS Importer:2022-05-27

Editorial: Immune-related adverse events for patients with lung cancer-volume II - Wang, Yusha; Wang, Xia; Zhan, Cheng; Frey, Benjamin; Gaipl, Udo; Shi, Hubing; Ma, Xuelei (Frontiers in Oncology, 2023)
CRIS-Team Scopus Importer:2023-12-15
Keywords: editorial; immune checkpoint inhibitors (ICIs); immune-related adverse events (irAEs); Immunotherapy; lung cancer

Editorial: Osteoarticular-immunological interplay in response to disease and therapy - Deloch, Lisa; Filkova, Maria; Tomcik, Michal (Frontiers in Immunology, 2022)
CRIS-Team Scopus Importer:2022-11-04
Keywords: B cell; bone; cartilage; osteoarthritis; osteoclast; radiotherapy; rheumatoid arthritis; T cell

Editorial: Radiation and the Immune System: Current Knowledge and Future Perspectives - Lumniczky, Katalin; Candeias, Serge M.; Gaipl, Udo; Frey, Benjamin (Frontiers in Immunology, 2017)
EVALuna2:32926

Editorial: Radioimmunotherapy—Translational Opportunities and Challenges - Gaipl, Udo; Multhoff, Gabriele; Pockley, A. Graham; Rödel, Franz (Frontiers in Oncology, 2020)
CRIS-Team Scopus Importer:2020-03-20
Keywords: immune checkpoint inhibitors; immunotherapy; radioimmunotherapy; radiotherapy; translational reseach; tumor stroma; vaccination

Editorial: Recent advances in genetic and proteomic biomarkers involved in the early detection of solid tumors - Li, Jitian; Chen, Apeng; Zhang, Ruowen; Li, Changwei; Zhou, Jianguo; Fang, Bin; Jiang, Yinan (Frontiers in Genetics, 2023)
CRIS-Team Scopus Importer:2023-09-29
Keywords: biomarker; detection; prognosis; solid tumor; treatment

Editorial: Systemic immune dysregulation in malignant disease: Insights, monitoring and therapeutic exploitation - Christopoulos, Petros; Gaipl, Udo (Frontiers in Oncology, 2023)
CRIS-Team Scopus Importer:2023-05-05
Keywords: biomarkers; cell therapies; immune checkpoint inhibitors; immune dysregulation; immune microenviroment

Editorial to radiation in multimodal tumor immune therapies—mechanisms and application - Frey, Benjamin; Gaipl, Udo (International Journal of Molecular Sciences, 2021)
CRIS-Team Scopus Importer:2021-07-30

Editorial: Uncovering Drug Resistance During Cancer Therapy - Wang, Haitao; Wang, Rui Hong; Zhou, Jianguo; Hou, Weilong; Wong, Ada Hang Heng (Frontiers in Genetics, 2022)
CRIS-Team Scopus Importer:2022-08-12
Keywords: biomarkers; cancer; cancer therapy; drug resistance; next generation sequencing; oncology

Education, training and registration of Medical Physics Experts across Europe - Maas, Ad J.J.; Lammertsma, Adriaan A.; Agius, Sam; Bert, Christoph; Byrne, Brenda; Caruana, Carmel J.; Gilligan, Paddy; Koutsouveli, Efi; Pace, Eric; Brambilla, Marco (Physica Medica, 2021)
From its inception, EFOMP has pursued a policy to improve and coordinate education and training of medical physicists across all its participating European countries. Several EFOMP policy statements on education and training have been published and surveys have been held to get an overview of the actual situation. At the beginning of 2020 a new survey was distributed amongst the 36 National Member Organizations (NMOs), in which questions were based on recommendations published in the most recent policy statements. Thirty-three of the NMOs (91%) responded, of which 22 indicated having a National Registration Scheme (NRS) for Medical Physics Experts (MPEs) in place. Another 6 indicated considering such a scheme. Results of the questionnaire showed that there was good correspondence between education and training programmes, i.e. a division between a BSc phase, an MSc phase and a clinical phase after completion of the MSc. Differences between NRSs were primarily seen in the availability and composition of a supervising committee and in the availability of guidelines for handling professional misconduct. In addition, some differences were seen in the topics that were part of the education and training programme. The goal of a universal (registered) MPE accepted by all European countries is still far away despite the progress being made. The new procedure for approving an existing NRS, which fulfils all EFOMP criteria is seen as an important step forward. Exchange of experience, knowledge, ideas and, above all, MPE trainees between European countries is seen as the best approach to achieve this goal.
CRIS-Team Scopus Importer:2021-06-04
Keywords: Education and training; European Federation of Organizations for Medical Physics; Medical Physics Expert; National registration scheme; Professional misconduct; Supervising committee

Efavirenz Has the Highest Anti-Proliferative Effect of Non-Nucleoside Reverse Transcriptase Inhibitors against Pancreatic Cancer Cells - Hecht, Markus; Erber, Sonja; Harrer, Thomas; Klinker, Hartwig; Roth, Thomas; Parsch, Hans; Fiebig, Nora; Fietkau, Rainer; Distel, Luitpold (PLoS ONE, 2015)
Cancer prevention and therapy in HIV-1-infected patients will play an important role in future. The non-nucleoside reverse transcriptase inhibitors (NNRTI) Efavirenz and Nevirapine are cytotoxic against cancer cells in vitro. As other NNRTIs have not been studied so far, all clinically used NNRTIs were tested and the in vitro toxic concentrations were compared to drug levels in patients to predict possible anti-cancer effects in vivo.Cytotoxicity was studied by Annexin-V-APC/7AAD staining and flow cytometry in the pancreatic cancer cell lines BxPC-3 and Panc-1 and confirmed by colony formation assays. The 50% effective cytotoxic concentrations (EC50) were calculated and compared to the blood levels in our patients and published data.The in vitro EC50 of the different drugs in the BxPC-3 pancreatic cancer cells were: Efavirenz 31.5 ?mol/l (= 9944 ng/ml), Nevirapine 239 ?mol/l (= 63,786 ng/ml), Etravirine 89.0 ?mol/l (= 38,740 ng/ml), Lersivirine 543 ?mol/l (= 168,523 ng/ml), Delavirdine 171 ?mol/l (= 78,072 ng/ml), Rilpivirine 24.4 ?mol/l (= 8941 ng/ml). As Efavirenz and Rilpivirine had the highest cytotoxic potential and Nevirapine is frequently used in HIV-1 positive patients, the results of these three drugs were further studied in Panc-1 pancreatic cancer cells and confirmed with colony formation assays. 205 patient blood levels of Efavirenz, 127 of Rilpivirine and 31 of Nevirapine were analyzed. The mean blood level of Efavirenz was 3587 ng/ml (range 162-15,363 ng/ml), of Rilpivirine 144 ng/ml (range 0-572 ng/ml) and of Nevirapine 4955 ng/ml (range 1856-8697 ng/ml). Blood levels from our patients and from published data had comparable Efavirenz levels to the in vitro toxic EC50 in about 1 to 5% of all patients.All studied NNRTIs were toxic against cancer cells. A low percentage of patients taking Efavirenz reached in vitro cytotoxic blood levels. It can be speculated that in HIV-1 positive patients having high Efavirenz blood levels pancreatic cancer incidence might be reduced. Efavirenz might be a new option in the treatment of cancer.
EVALuna2:13144

Effective local control of advanced soft tissue sarcoma with neoadjuvant chemoradiotherapy and surgery: A single institutional experience - Stubbe, Franziska; Agaimy, Abbas; Ott, O.; Lettmaier, S.; Vassos, N.; Croner, R.; Hohenberger, Werner; Fietkau, Rainer; Semrau, S. (Cancer Radiotherapie, 2016)
There is a sound theoretical basis but little clinical evidence substantiating the benefits of concurrent chemoradiotherapy with two-drug chemotherapy for locally advanced soft tissue sarcomas. Our five-year data on the feasibility and effectiveness of neoadjuvant chemoradiotherapy with systemically effective doses of adriamycin and ifosfamide combined is presented here.Between 2000 and 2011, 53 patients with UICC (2010) stage I (n=1, 1.9%), II (n=12, 22.7%) or III (n=40, 75.5%) nonmetastatic soft tissue sarcoma received neoadjuvant chemoradiotherapy with ifosfamide (1.5g/m(2)/day, d1-5, q28) and doxorubicin (50mg/m(2)/day, d3, q28) plus concurrent radiotherapy with a target dose of 50-64Gy (median 60Gy). The treatment of 34 patients (64.2%) was combined with hyperthermia.At five years, the local control rate was 89.9% (±5.7%), distant metastasis-free survival 66.6% (±7.6%), and survival 83.3% (±6%). The R0 resection rate was 81.1%. Radiotherapy was completed as planned in all patients and chemotherapy in 42/53 (70.2%). Grades III (n=21, 29.6%) and IV (n=18, 34%) leukopenia was the main acute adverse event. All acute and chronic non-hematologic toxicities were moderate.Neoadjuvant chemoradiotherapy for soft tissue sarcoma is associated with good feasibility, manageable acute and late toxicities, and high local efficacy.
EVALuna2:6741

Effective local control of vertebral metastases by simultaneous integrated boost radiotherapy: preliminary results - Lubgan, Dorota; Ziegaus, Anke; Semrau, Sabine; Lambrecht, Ulrike; Lettmaier, Sebastian; Fietkau, Rainer (Strahlentherapie und Onkologie, 2015)
The primary endpoint was to improve local tumour control of patients with metastatic spinal tumours by stereotactic body radiotherapy (SBRT) and dose escalation by simultaneous, integrated boost (PTV-boost). We used a whole vertebral body (PTV-elective) contouring approach. Secondary endpoints were severity of acute and chronic adverse effects and overall survival.In all, 33 patients with metastases of the vertebral column were treated at Erlangen University Hospital. SBRT was given in 12 or 10 fractions. The metastatic lesion (PTV-boost) received 3.6 Gy (range 3.0-4.51 Gy) per fraction for a total of 42.0 Gy (24.36-48.0 Gy) and the whole vertebra (PTV-elective) received 2.85 Gy (range 1.8-3.6 Gy) per fraction for a total of 32.39 Gy (range 21.60-38.0 Gy). Patients were followed up every 3 months.Local control rate of all patients was 93% at 12 and 24 months. The overall survival rate was 54% at 12 months, 38% at 24 months and 18% at 36 months. No radiation myelopathy occurred. The most frequently observed adverse events in 3 cases was oesophagitis grade 2.SBRT with simultaneous, integrated boost was associated with excellent local control of 93% after 24 months. This result shows the possibility of delivering escalated doses to the target while still keeping the incidence of side effects low. This study forms the basis for a future randomised controlled trial comparing conventional radiotherapy (10 fractions of 3 Gy) with hypofractionated dose intensified SBRT (12 fractions of 3 Gy + integrated boost 12 fractions of 4 Gy) for improvement of local tumour control and pain.
EVALuna2:18283

Effective long-term local results and prognostic factors after fractionated stereotactic radiotherapy of 257 intracranial meningeoma - Lubgan, Dorota; Rutzner, Sandra; Semrau, S.; Lambrecht, U.; Roessler, K.; Buchfelder, Michael; Fietkau, Rainer (2016)
EVALuna2:18329

Effectiveness of ablative Irradiation of all Metastases versus Irradiation of a singular Metastasis in Combination with Immunocheckpoint Inhibitors - clinical Evaluation of prospective STICI Study - Schubert, P.; Schweizer, C.; Roesch, Johannes; Haderlein, Marlen; Rutzner, Sandra; Semrau, Sabine; Donaubauer, Anna-Jasmina; Zhou, Jianguo; Frey, Benjamin; Fietkau, Rainer; Gaipl, Udo; Hecht, Markus (STRAHLENTHERAPIE UND ONKOLOGIE, 2020)
CRIS-Team WoS Importer:2020-10-02

Effect of Citrate- and Gold-Stabilized Superparamagnetic Iron Oxide Nanoparticles on Head and Neck Tumor Cell Lines during Combination Therapy with Ionizing Radiation - Schreiber, Christoph; Franzen, Tim; Hildebrand, Laura; Stein, René; Friedrich, Bernhard; Tietze, Rainer; Fietkau, Rainer; Distel, Luitpold (Bioengineering, 2022)
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. They are associated with alcohol and tobacco consumption, as well as infection with human papillomaviruses (HPV). Therapeutic options include radiochemotherapy, surgery or chemotherapy. Nanoparticles are becoming more and more important in medicine. They can be used diagnostically, but also therapeutically. In order to provide therapeutic alternatives in the treatment of HNSCC, the effect of citrate-coated superparamagnetic iron oxide nanoparticles (Citrate-SPIONs) and gold-coated superparamagnetic iron oxide nanoparticles (Au-SPIONs) in combination with ionizing irradiation (IR) on two HPV positive and two HPV negative HNSCC and healthy fibroblasts and keratinocytes cell lines were tested. Effects on apoptosis and necrosis were analyzed by using flow cytometry. Cell survival studies were performed with a colony formation assay. To better understand where the SPIONs interact, light microscopy images and immunofluorescence studies were performed. The HNSCC and healthy cell lines showed different responses to the investigated SPIONs. The cytotoxic effects of SPIONs, in combination with IR, are dependent on the type of SPIONs, the dose administered and the cell type treated. They are independent of HPV status. Reasons for the different cytotoxic effect are probably the different compositions of the SPIONs and the related different interaction of the SPIONs intracellularly and paramembranously, which lead to different strong formations of double strand breaks.
CRIS-Team WoS Importer:2023-01-13

Effect of CT-based attenuation correction on uptake ratios in skeletal SPECT - Schulz, Volkmar; Nickel, Ingo; Nömayr, Anton; Vija, Alexander Hans; Hocke, Carsten; Hornegger, Joachim; Bautz, Werner; Römer, Wolfgang; Kuwert, Torsten (Nuklearmedizin-Nuclear Medicine, 2007)
The aim of this study was to determine the clinical relevance of compensating SPECT data for patient specific attenuation by the use of CT data simultaneously acquired with SPECT/CT when analyzing the skeletal uptake of polyphosphonates (DPD). Furthermore, the influence of misregistration between SPECT and CT data on uptake ratios was investigated. Methods: Thirty-six data sets from bone SPECTs performed on a hybrid SPECT/CT system were retrospectively analyzed. Using regions of interest (ROIs), raw counts were determined in the fifth lumbar vertebral body, its facet joints, both anterior iliacal spinae, and of the whole transversal slice. ROI measurements were performed in uncorrected (NAC) and attenuation-corrected (AC) images. Furthermore, the ROI measurements were also performed in AC scans in which SPECT and CT images had been misaligned by 1 cm in one dimension beforehand (ACX, ACY, ACZ). Results: After AC, DPD uptake ratios differed significantly from the NAC values in all regions studied ranging from 32% for the left facet joint to 39% for the vertebral body. AC using misaligned pairs of patient data sets led to a significant change of whole-slice uptake ratios whose differences ranged from 3,5 to 25%. For ACX, the average left-to-right ratio of the facet joints was by 8% and for the superior iliacal spines by 31% lower than the values determined for the matched images (p <0.05). Conclusions: AC significantly affects DPD uptake ratios. Furthermore, misalignment between SPECT and CT may introduce significant errors in quantification, potentially also affecting left-to-right ratios. Therefore, at clinical evaluation of attenuation-corrected scans special attention should be given to possible misalignments between SPECT and CT. © 2007 Schattauer GmbH.

Effect of hyperthermia and radiation therapy sequence on cell death and the immune phenotype of breast cancer cells - Sengedorj, Azzaya; Hader, Michael; Rückert, Michael; Frey, Benjamin; Fietkau, Rainer; Ott, Oliver; Scheidegger, S.; Barba, S. M.; Gaipl, Udo (STRAHLENTHERAPIE UND ONKOLOGIE, 2022)
CRIS-Team WoS Importer:2022-06-03

Effect of Radiotherapy and Chemotherapy on the Immunophenotype of Head and Neck Cancer Cells and the consecutive Activation of dendritic Cells - Grottker, F.; Frey, Benjamin; Gehre, S.; Reichardt, Clara; Sengedorj, Azzaya; Hecht, Markus; Fietkau, Rainer; Rieckmann, T.; Gostian, Antoniu-Oreste; Gaipl, Udo; Rückert, Michael (STRAHLENTHERAPIE UND ONKOLOGIE, 2022)
CRIS-Team WoS Importer:2022-06-03

Effect of the AMPA Receptor Inhibitor Perampanel in Combination Therapy with ionizing Radiation on Glioblastoma Cells and Fibroblasts - Knabe, A.; Stritzelberger, Jenny; Fietkau, Rainer; Distel, Luitpold (STRAHLENTHERAPIE UND ONKOLOGIE, 2021)
CRIS-Team WoS Importer:2021-07-16

Effect of the kinase-inhibitor Palbociclib on radio-therapeutic treatment in a 3D cell culture model - Jost, Tina; Hecht, Markus; Fietkau, Rainer; Distel, Luitpold (2018)
EVALuna2:36492

Effects of a Caregiver on the Quality of Life of Cancer Patients during Radiochemotherapy and Improvement Potential through Integration of the Caregiver in the Therapy - Wittenstein, Katharina; Fietkau, Rainer; Distel, Luitpold; Lebensqualitat, Studiengruppe (2017)
EVALuna2:32898

Effects of BRCA1 Mutations on Radiation Resistance and Immunophenotype in Breast Cancer Cells - Classen, S.; Rahlf, E.; Jungwirth, J.; Gehre, S.; Rückert, Michael; Rothkamm, K.; Petersen, C.; Gaipl, Udo; Pospiech, H.; Borgmann, K. (STRAHLENTHERAPIE UND ONKOLOGIE, 2022)
CRIS-Team WoS Importer:2022-06-03

Effects of Combination Therapy of Kinase Inhibitors and ionizing Radiation on ENT Tumor Cell Lines and Normal Tissue Cells - Faulhaber, E. -M; Scheper, J.; Jost, Tina; Hecht, Markus; Fietkau, Rainer; Distel, Luitpold (STRAHLENTHERAPIE UND ONKOLOGIE, 2020)
CRIS-Team WoS Importer:2020-10-02

Effects of Hippocampal Sparing Radiotherapy on Brain Microstructure—A Diffusion Tensor Imaging Analysis - Dinkel, Johannes; Lahmer, Godehard; Mennecke, Angelika; Hock, Stefan; Richter-Schmidinger, Tanja; Fietkau, Rainer; Distel, Luitpold; Putz, Florian; Dörfler, Arnd; Schmidt, Manuel (Brain Sciences, 2022)
Hippocampal-sparing radiotherapy (HSR) is a promising approach to alleviate cognitive side effects following cranial radiotherapy. Microstructural brain changes after irradiation have been demonstrated using Diffusion Tensor Imaging (DTI). However, evidence is conflicting for certain parameters and anatomic structures. This study examines the effects of radiation on white matter and hippocampal microstructure using DTI and evaluates whether these may be mitigated using HSR. A total of 35 tumor patients undergoing a prospective randomized controlled trial receiving either conventional or HSR underwent DTI before as well as 6, 12, 18, 24, and 30 (±3) months after radiotherapy. Fractional Anisotropy (FA), Mean Diffusivity (MD), Axial Diffusivity (AD), and Radial Diffusivity (RD) were measured in the hippocampus (CA), temporal, and frontal lobe white matter (TL, FL), and corpus callosum (CC). Longitudinal analysis was performed using linear mixed models. Analysis of the entire patient collective demonstrated an overall FACC decrease and RDCC increase compared to baseline in all follow-ups; ADCC decreased after 6 months, and MDCC increased after 12 months (p ≤ 0.001, 0.001, 0.007, 0.018). ADTL decreased after 24 and 30 months (p ≤ 0.004, 0.009). Hippocampal FA increased after 6 and 12 months, driven by a distinct increase in ADCA and MDCA, with RDCA not increasing until 30 months after radiotherapy (p ≤ 0.011, 0.039, 0.005, 0.040, 0.019). Mean radiation dose correlated positively with hippocampal FA (p < 0.001). These findings may indicate complex pathophysiological changes in cerebral microstructures after radiation, insufficiently explained by conventional DTI models. Hippocampal microstructure differed between patients undergoing HSR and conventional cranial radiotherapy after 6 months with a higher ADCA in the HSR subgroup (p ≤ 0.034).
CRIS-Team Scopus Importer:2022-07-22
Keywords: cognitive impairment; cranial radiotherapy; diffusion tensor imaging; fractional anisotropy; hippocampal sparing radiotherapy; hippocampus

Effects of Radiotherapy on the Kinetics of Immune Checkpoint Molecule Expression in Tumor Cells and their radioresistant Clones - Siegert, Juliane; Rückert, Michael; Meyer, F.; Borgmann, K.; Fietkau, Rainer; Frey, Benjamin; Gaipl, Udo (STRAHLENTHERAPIE UND ONKOLOGIE, 2022)
CRIS-Team WoS Importer:2022-06-03

Effects of Radon-Spa-Therapy on Patients with musculoskeletal Diseases - Becker, Ina; Donaubauer, Anna-Jasmina; Klein, G.; Fournier, C.; Fietkau, Rainer; Frey, Benjamin; Gaipl, Udo (STRAHLENTHERAPIE UND ONKOLOGIE, 2020)
CRIS-Team WoS Importer:2020-10-02

Effects of whole-body electromyostimulation combined with individualized nutritional support on body composition in patients with advanced cancer: a controlled pilot trial - Schink, Kristin; Herrmann, Hans J.; Schwappacher, Raphaela; Meyer, Julia; Orlemann, Till; Waldmann, Elisabeth; Wullich, Bernd; Kahlmeyer, Andreas; Fietkau, Rainer; Lubgan, Dorota; Beckmann, Matthias; Hack, Carolin; et al. (BMC Cancer, 2018)
BACKGROUND: Physical exercise and nutritional treatment are promising measures to prevent muscle wasting that is frequently observed in advanced-stage cancer patients. However, conventional exercise is not always suitable for these patients due to physical weakness and therapeutic side effects. In this pilot study, we examined the effect of a combined approach of the novel training method whole-body electromyostimulation (WB-EMS) and individualized nutritional support on body composition with primary focus on skeletal muscle mass in advanced cancer patients under oncological treatment. METHODS: In a non-randomized controlled trial design patients (56.5% male; 59.9 ± 12.7 years) with advanced solid tumors (UICC III/IV, N = 131) undergoing anti-cancer therapy were allocated to a usual care control group (n = 35) receiving individualized nutritional support or to an intervention group (n = 96) that additionally performed a supervised physical exercise program in form of 20 min WB-EMS sessions (bipolar, 85 Hz) 2×/week for 12 weeks. The primary outcome of skeletal muscle mass and secondary outcomes of body composition, body weight and hand grip strength were measured at baseline, in weeks 4, 8 and 12 by bioelectrical impedance analysis and hand dynamometer. Effects of WB-EMS were estimated by linear mixed models. Secondary outcomes of physical function, hematological and blood chemistry parameters, quality of life and fatigue were assessed at baseline and week 12. Changes were analyzed by t-tests, Wilcoxon signed-rank or Mann-Whitney-U-tests. RESULTS: Twenty-four patients of the control and 58 of the WB-EMS group completed the 12-week trial. Patients of the WB-EMS group had a significantly higher skeletal muscle mass (0.53 kg [0.08, 0.98]; p = 0.022) and body weight (1.02 kg [0.05, 1.98]; p = 0.039) compared to controls at the end of intervention. WB-EMS also significantly improved physical function and performance status (p < 0.05). No significant differences of changes in quality of life, fatigue and blood parameters were detected between the study groups after 12 weeks. CONCLUSIONS: Supervised WB-EMS training is a safe strength training method and combined with nutritional support it shows promising effects against muscle wasting and on physical function in advanced-stage cancer patients undergoing treatment. TRIAL REGISTRATION: ClinicalTrials.gov NCT02293239 (Date: November 18, 2014).
EVALuna2:35141

Efficacy and safety of Trifluridin/Tipiracil (FTD/TPI) (Lonsurf (R)) in patients with metastatic colorectal cancer (CRC) in clinical-routine use - Cao, J.; Wiesweg, M.; Fuchs, M.; Stein, A.; Karthaus, M.; Lettmaier, S.; Kretzschmar, A.; Draube, A.; Ettrich, T.; Ruessel, J.; Mueller, C.; Rafiyan, M. -R; et al. (2018)
EVALuna2:36527

E-Field Patterns of Coaxial MW Antennas for Combined Thermo-Brachytherapy - Erb, J.; Engelbrecht, Rainer; Schaller, Gerhard; Ross, D.; Seegenschmiedt, Heinrich; Fietkau, Rainer; Sauer, R. (Deutsche Brachytherapie-Konferenz, 1993)
UnivIS-Import:2015-04-16:Pub.1993.tech.IE.LEH.efield

EGFR inhibition in NSCLC tumor cell lines : Influence on cell cycle and tumor control - Gaipl, Udo (Strahlentherapie und Onkologie, 2016)
EVALuna2:32935

ELDORANDO - Pembrolizumab compared with methotrexate in elderly, frail or cisplatin-ineligible patients with relapsed or metastatic squamous cell carcinoma of the head and neck (RM-SCCHN) (ELDORANDO-AIO-KHT-0115) - Klinghammer, K.; Graeven, U.; Ivanyi, P.; Dietz, A.; Hahn, D.; Hackenberg, S.; Kasper, S.; Fietkau, Rainer; Moulin, J. -C; Pink, D.; Schaaf, M.; Grunwald, (ONCOLOGY RESEARCH AND TREATMENT, 2021)
CRIS-Team WoS Importer:2022-03-25

Electromagnetic tracking for treatment verification in interstitial brachytherapy - Bert, Christoph; Kellermeier, Markus; Tanderup, Kari (Journal of Contemporary Brachytherapy, 2016)
Electromagnetic tracking (EMT) is used in several medical fields to determine the position and orientation of dedicated sensors, e.g., attached to surgical tools. Recently, EMT has been introduced to brachytherapy for implant reconstruction and error detection. The manuscript briefly summarizes the main issues of EMT and error detection in brachytherapy. The potential and complementarity of EMT as treatment verification technology will be discussed in relation toin vivodosimetry and imaging.
EVALuna2:33051

Electromagnetic tracking in interstitial brachytherapy: A systematic review - Sauer, Birte; Dürrbeck, Christopher; Bert, Christoph (Frontiers in Physics, 2022)
Brachytherapy is a well-established treatment option for different cancer types. One treatment option, namely temporary afterloading brachytherapy, utilizes an encapsulated radioactive source, which is guided through implanted applicators to pre-defined dwell positions, to deliver highly conformal and concentrated doses to the target volume. However, treatment errors and uncertainties might still occur. The treatment therefore requires a stringent verification on an individual patient level, particularly in the form of applicator reconstruction. Electromagnetic tracking (EMT) is a possible verification option whose application neither relies on direct line of sight nor does it increase the radiation exposure. However, its systematic clinical application is not yet realized. This review will separate the concept of treatment verification through the use of electromagnetic tracking into four focus groups and categorize the relevant papers within said groups. The four focus groups are geometric assessment, applicator reconstruction, patient-individual quality assurance and adaptive treatment planning. The reviewed papers can be mainly sorted into the focus groups of geometric assessment and applicator reconstruction underlining the potential of EMT as an asset for reconstruction and localization. A smaller group of papers can be associated with patient-individual quality assurance where the detection of implant variations such as swaps within the connector cohort or single catheter shifts take center stage. The final focus group, adaptive treatment planning, is sparsely represented, yet the feasibility of an adaptive treatment course can be derived. This review will close with a discussion of possible improvements and illustrate the path ahead to clinical implementation.
CRIS-Team WoS Importer:2022-10-14

Electronic Support for Retrospective Analysis in the Field of Radiation Oncology: Proof of Principle Using an Example of Fractionated Stereotactic Radiotherapy of 251 Meningioma Patients - Rutzner, Sandra; Fietkau, Rainer; Ganslandt, Thomas; Prokosch, Hans-Ulrich; Lubgan, Dorota (Frontiers in Oncology, 2017)
The purpose of this study is to verify the possible benefit of a clinical data warehouse (DWH) for retrospective analysis in the field of radiation oncology.We manually and electronically (using DWH) evaluated demographic, radiotherapy, and outcome data from 251 meningioma patients, who were irradiated from January 2002 to January 2015 at the Department of Radiation Oncology of the Erlangen University Hospital. Furthermore, we linked the Oncology Information System (OIS) MOSAIQ(®) to the DWH in order to gain access to irradiation data. We compared the manual and electronic data retrieval method in terms of congruence of data, corresponding time, and personal requirements (physician, physicist, scientific associate).The electronically supported data retrieval (DWH) showed an average of 93.9% correct data and significantly (p = 0.009) better result compared to manual data retrieval (91.2%). Utilizing a DWH enables the user to replace large amounts of manual activities (668 h), offers the ability to significantly reduce data collection time and labor demand (35 h), while simultaneously improving data quality. In our case, work time for manually data retrieval was 637 h for the scientific assistant, 26 h for the medical physicist, and 5 h for the physician (total 668 h).Our study shows that a DWH is particularly useful for retrospective analysis in the radiation oncology field. Routine clinical data for a large patient group can be provided ready for analysis to the scientist and data collection time can be significantly reduced. Furthermore, linking multiple data sources in a DWH offers the ability to improve data quality for retrospective analysis, and future research can be simplified.
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Electrothermic effects of microwave heating on B16 melanoma cells - examinations with a semi-continuous plug flow-like reactor - Drescher, C.; Derer, Anja; Rosin, A.; Gerdes, T.; Willert-Porada, M.; Wadepohl, M.; Fietkau, Rainer; Gaipl, Udo; Frey, Benjamin (2017)
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Elucidation of the Application of Blood Test Biomarkers to Predict Immune-Related Adverse Events in Atezolizumab-Treated NSCLC Patients Using Machine Learning Methods - Zhou, Jian-Guo; Wong, Ada Hang-Heng; Wang, Haitao; Tan, Fangya; Chen, Xiaofei; Jin, Su-Han; He, Si-Si; Shen, Gang; Wang, Yun-Jia; Frey, Benjamin; Fietkau, Rainer; Hecht, Markus; et al. (Frontiers in Immunology, 2022)
BackgroundDevelopment of severe immune-related adverse events (irAEs) is a major predicament to stop treatment with immune checkpoint inhibitors, even though tumor progression is suppressed. However, no effective early phase biomarker has been established to predict irAE until now. MethodThis study retrospectively used the data of four international, multi-center clinical trials to investigate the application of blood test biomarkers to predict irAEs in atezolizumab-treated advanced non-small cell lung cancer (NSCLC) patients. Seven machine learning methods were exploited to dissect the importance score of 21 blood test biomarkers after 1,000 simulations by the training cohort consisting of 80%, 70%, and 60% of the combined cohort with 1,320 eligible patients. ResultsXGBoost and LASSO exhibited the best performance in this study with relatively higher consistency between the training and test cohorts. The best area under the curve (AUC) was obtained by a 10-biomarker panel using the XGBoost method for the 8:2 training:test cohort ratio (training cohort AUC = 0.692, test cohort AUC = 0.681). This panel could be further narrowed down to a three-biomarker panel consisting of C-reactive protein (CRP), platelet-to-lymphocyte ratio (PLR), and thyroid-stimulating hormone (TSH) with a small median AUC difference using the XGBoost method [for the 8:2 training:test cohort ratio, training cohort AUC difference = -0.035 (p < 0.0001), and test cohort AUC difference = 0.001 (p=0.965)]. ConclusionBlood test biomarkers currently do not have sufficient predictive power to predict irAE development in atezolizumab-treated advanced NSCLC patients. Nevertheless, biomarkers related to adaptive immunity and liver or thyroid dysfunction warrant further investigation.
CRIS-Team WoS Importer:2022-07-29

Encapsulation of hydrophobic drugs in shell-by- shell coated nanoparticles for radio—and chemotherapy—an in Vitro study - Klein, Stefanie; Luchs, Tobias; Leng, Andreas; Distel, Luitpold; Neuhuber, Winfried; Hirsch, Andreas (Bioengineering, 2020)
Our research objective was to develop novel drug delivery vehicles consisting of TiO2 and Al2O3 nanoparticles encapsulated by a bilayer shell that allows the reversible embedment of hydrophobic drugs. The first shell is formed by covalent binding of hydrophobic phosphonic acid at the metal oxide surface. The second shell composed of amphiphilic sodium dodecylbenzenesulfonate emerges by self-aggregation driven by hydrophobic interactions between the dodecylbenzene moiety and the hydrophobic first shell. The resulting double layer provides hydrophobic pockets suited for the intake of hydrophobic drugs. The nanoparticles were loaded with the anticancer drugs quercetin and 7-amino-4-methylcoumarin. Irradiation with X-rays was observed to release the potential anticancer drugs into the cytoplasm. In Michigan Cancer Foundation (MCF)-10 A cells, quercetin and 7-amino-4-methylcoumarin acted as antioxidants by protecting the non-tumorigenic cells from harmful radiation effects. In contrast, these agents increased the reactive oxygen species (ROS) formation in cancerous MCF-7 cells. Quercetin and 7-amino-4-methylcoumarin were shown to induce apoptosis via the mitochondrial pathway in cancer cells by determining an increase in TUNEL-positive cells and a decrease in mitochondrial membrane potential after irradiation. After X-ray irradiation, the survival fraction of MCF-7 cells with drug-loaded nanoparticles considerably decreased, which demonstrates the excellent performance of the double-layer stabilized nanoparticles as drug delivery vehicles.
CRIS-Team Scopus Importer:2020-10-23
Keywords: Al; Chemotherapy; Drug delivery; Quercetin; Radiotherapy; Shell-by-shell nanoparticles; TiO

Endocrine therapy with accelerated Partial breast irradiatiOn or exclusive ultra-accelerated Partial breast irradiation for women aged >= 60 years with Early-stage breast cancer (EPOPE): The rationale for a GEC-ESTRO randomized phase III-controlled trial - Hannoun-Levi, Jean-Michel; Chamorey, Emmanuel; Boulahssass, Rabia; Polgar, Csaba; Strnad, Vratislav (Clinical and Translational Radiation Oncology, 2021)
Purpose: Breast cancer in the elderly has become a public health concern; there is a need to re-design its treatment with a view to de-escalation. Our paper sets out the rationale for a phase 3 randomized trial to evaluate less burdensome adjuvant procedures that remain effective and efficient.
CRIS-Team WoS Importer:2021-07-16

Enhanced In Vitro Biocompatibility and Water Dispersibility of Magnetite and Cobalt Ferrite Nanoparticles Employed as ROS Formation Enhancer in Radiation Cancer Therapy - Klein, Stefanie; Kizaloglu, Melek; Portilla Berlanga, Luis; Park, Hyoungwon; Rejek, Tobias; Hümmer, Julian; Meyer, Karsten; Hock, Rainer; Distel, Luitpold; Halik, Marcus; Kryschi, Carola (Small, 2018)

Enhanced tumour regression in a patient of liposarcoma treated with radiotherapy and hyperthermia: Hint for dynamic immunomodulation by hyperthermia - Datta, Niloy Ranjan; Grobholz, Rainer; Puric, Emsad; Bode-Lesniewska, Beata; Lomax, Nicoletta; Khan, Shaka; Gaipl, Udo; Fuchs, Bruno; Bodis, Stephan (International Journal of Hyperthermia, 2015)
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Enhancer hijacking activates oncogenic transcription factor NR4A3 in acinic cell carcinomas of the salivary glands - Haller, Florian; Bieg, Matthias; Will, Rainer; Koerner, Cindy; Weichenhan, Dieter; Bott, Alexander; Ishaque, Naveed; Lutsik, Pavlo; Moskalev, Evgeny; Müller, Susanna; Baehr, Marion; Woerner, Angelika; et al. (Nature Communications, 2019)
The molecular pathogenesis of salivary gland acinic cell carcinoma (AciCC) is poorly understood. The secretory Ca-binding phosphoprotein (SCPP) gene cluster at 4q13 encodes structurally related phosphoproteins of which some are specifically expressed at high levels in the salivary glands and constitute major components of saliva. Here we report on recurrent rearrangements [t(4;9)(q13;q31)] in AciCC that translocate active enhancer regions from the SCPP gene cluster to the region upstream of Nuclear Receptor Subfamily 4 Group A Member 3 (NR4A3) at 9q31. We show that NR4A3 is specifically upregulated in AciCCs, and that active chromatin regions and gene expression signatures in AciCCs are highly correlated with the NR4A3 transcription factor binding motif. Overexpression of NR4A3 in mouse salivary gland cells increases expression of known NR4A3 target genes and has a stimulatory functional effect on cell proliferation. We conclude that NR4A3 is upregulated through enhancer hijacking and has important oncogenic functions in AciCC.
EVALuna2:35381

Enhancing the Effect of Combination Therapy with the PARP Inhibitor Talazoparib and ionizing Radiation on Melanoma Cell Lines - Proebstle, Stephanie; Jost, Tina; Buerkel, F.; Hecht, Markus; Fietkau, Rainer; Distel, Luitpold (2018)
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Erlangen Experience on radiosurgical Treatment for Trigeminal Neuralgia - Lettmaier, S.; Putz, Florian; Distel, Luitpold; Bischoff, B.; Bozhkov, Y.; Merkel, Andreas; Lambrecht, U.; Koca, S.; Fietkau, Rainer (2017)
EVALuna2:32886

Erlangen Experiences with Durvalumab Preservation Therapy after defnitive Radiochemotherapy in Patients with NSCLC: First Survival and Toxicity Data from clinical Routine - Lettmaier, Sebastian; Hecht, Markus; Fietkau, Rainer (STRAHLENTHERAPIE UND ONKOLOGIE, 2020)
CRIS-Team WoS Importer:2020-10-02

Erratum to: DEGRO practical guidelines for radiotherapy of breast cancer V: Therapy for locally advanced and inflammatory breast cancer, as well as local therapy in cases with synchronous distant metastases - Budach, Wilfried; Matuschek, C.; Boelke, E.; Dunst, J.; Feyer, P.; Fietkau, Rainer; Haase, W.; Harms, W.; Piroth, Marc D.; Sautter-Bihl, M. -L.; Sedlmayer, F.; Souchon, R.; et al. (Strahlentherapie und Onkologie, 2015)
EVALuna2:18274

Erratum to: Primary glioblastoma multiforme tumors and recurrence: comparative analysis of the danger signals HMGB1, HSP70, and calreticulin - Muth, Carolin; Rubner, Yvonne; Semrau, Sabine; Rühle, Paul-Friedrich; Frey, Benjamin; Strnad, Annedore; Buslei, Rolf; Fietkau, Rainer; Gaipl, Udo (Strahlentherapie und Onkologie, 2016)
EVALuna2:7315

Erratum to: Stress examination of flexor tendon pulley rupture in the crimp grip position: a 1.5-Tesla MRI cadaver study - Bayer, Thomas; Fries, Simon; Schweizer, Andreas; Schoeffl, Isabelle; Janka, Rolf Matthias; Bongartz, Georg (Skeletal Radiology, 2015)
EVALuna2:14346

Error detection using an electromagnetic tracking system in multi-catheter breast interstitial brachytherapy - Masitho, Siti; Kallis, Karoline; Strnad, Vratislav; Fietkau, Rainer; Bert, Christoph (Physics in Medicine and Biology, 2019)
The hybrid treatment delivery system (HTDS) has been proposed as a possible option for a quality assurance in the multi-catheter interstitial brachytherapy for breast cancer patients. The system, which consists out of a prototype afterloader with an integrated electromagnetic tracking (EMT) sensor and an EMT system, allows the automatic measurement of implanted catheters. To test the feasibility of the system for error detection, possible treatment planning errors and treatment delivery errors were simulated. Planning errors such as an incorrect offset value, an incorrect indexer length, tip/connector end swaps, and partial swaps, and; treatment delivery errors such as catheter shifts and catheter connection swaps were manually simulated using phantoms. An in-house Matlab routine was used to assess geometrical deviations between the dwell positions defined based on CT and EMT measurement. Additionally, the influence of implant motion on the detection ability of the system was assessed. An algorithm for the detection and specification of errors based on the error simulation results was developed. At the University Hospital Erlangen, a patient study is ongoing, where errors in patient data were analyzed using the proposed algorithm. All simulated planning errors were detected. Catheter connection swaps can be detected 100% of the time. A shift detection rate of >97% was observed for shifts larger than 1.1 mm, both in the static and the motion measurements. Catheter reconstruction uncertainties and catheter shifts <2 mm were found to be the most common treatment planning and delivery errors in patient data. HTDS proved to be a reliable method for error detection.
CRIS-Team Scopus Importer:2019-10-29

Error detection using an electromagnetic tracking system in multicatheter interstitial brachytherapy - Masitho, S.; Kallis, Karoline; Strnad, Vratislav; Fietkau, Rainer; Bert, Christoph (RADIOTHERAPY AND ONCOLOGY, 2019)
CRIS-Team WoS Importer:2019-06-18

Erste erfolgversprechende Ergebnisse der Kombination aus Strahlentherapie und Pembrolizumab beim metastasierten nichtkleinzelligen Lungenkarzinom - Hecht, Markus; Gaipl, Udo; Fietkau, Rainer (Strahlentherapie und Onkologie, 2020)
CRIS-Team Scopus Importer:2020-02-25

Essential role of radiation therapy for the treatment of pancreatic cancer : Novel study concepts and established treatment recommendations - Dobiasch, Sophie; Goerig, Nicole; Fietkau, Rainer; Combs, Stephanie E. (Strahlentherapie und Onkologie, 2018)
BACKGROUND: Pancreatic cancer is one of the most aggressive human tumors and the incidence has increased over the last 6 years. In the majority of cases the disease is already in an advanced stage at the time of diagnosis where surgery, the only curative treatment, is no longer an option and explains the still abysmal overall survival. The role of radiation therapy as treatment option for patients with pancreatic cancer is controversially discussed although radiation oncology has emerged as a central pillar in the combined oncological treatment. PURPOSE: The present manuscript gives an overview of advanced radiotherapeutic strategies in the context of chemotherapy and surgery according to the current American Society of Clinical Oncology (ASCO) guidelines in comparison with the German guidelines and to elucidate the role of radiation therapy for the treatment of pancreatic cancer. CONCLUSION: Advanced modern radiotherapeutic techniques in combination with individualized high-precision radiation concepts are new therapeutic approaches for pancreatic cancer in a multimodal setting with tolerable side effects. Several clinical studies together with experimental approaches are in process, to deliver further evidence and ultimately allow true personalized medicine.
EVALuna2:36445

Establishment of a FACS Assay for Screening of (TEMRA) Cells in Glioblastoma Patients - Scheer, I.; Becker, Ina; Donaubauer, Anna-Jasmina; Fietkau, Rainer; Gaipl, Udo; Frey, Benjamin (STRAHLENTHERAPIE UND ONKOLOGIE, 2021)
CRIS-Team WoS Importer:2021-07-16

Establishment of a Multicolor Flow Cytometry Assay for Screening the NK Cells in Cancer Patients - Becker, Ina; Donaubauer, Anna-Jasmina; Multhoff, G.; Fietkau, Rainer; Frey, Benjamin; Gaipl, Udo (STRAHLENTHERAPIE UND ONKOLOGIE, 2022)
CRIS-Team WoS Importer:2022-06-03

Estimating follow-up CTs from geometric deformations of catheter implants in interstitial breast brachytherapy: A feasibility study using electromagnetic tracking - Dürrbeck, Christopher; Schulz, Moritz; Pflaum, Leonie; Kallis, Karoline; Geimer, Tobias; Abu-Hossin, Nadin; Strnad, Vratislav; Maier, Andreas; Fietkau, Rainer; Bert, Christoph (Medical Physics, 2023)
Background: Electromagnetic tracking (EMT) systems have been shown to provide valuable information on the geometry of catheter implants in breast cancer patients undergoing interstitial brachytherapy (iBT). In the context of an extended patient-specific, pre-treatment verification, EMT can play a key role in determining the potential need and, if applicable, the appropriate time for treatment adaptation. To detect dosimetric shortcomings the relative position between catheters, and target volume and critical structures must be known. Since EMT cannot provide the anatomical context and standard imaging techniques such as cone-beam CT are not yet available in most brachytherapy suites, it is not possible to detect anatomic changes on a daily or fraction basis, so the need for adaptive planning cannot be identified. Purpose: The aim of this feasibility study is to develop and evaluate a technique capable of estimating follow-up CTs at any time based on the initial treatment planning CT (PCT) and surrogate information about changes of the implant geometry from an EMT system. Methods: A deformation vector field is calculated from two different implant reconstructions acquired in treatment position through EMT, the first immediately after the PCT and the second at another time point during the course of treatment. The calculation is based on discrete displacement vectors of pairs of control and target points. These are extrapolated by means of different radial basis functions in order to cover the entire CT volume. The adequate parameters for the calculation of the deformation field were identified. By warping the PCT according to the deformation field, one obtains an estimated CT (ECT) that reflects the geometric changes. For the proof of concept, ECTs were computed for the time point of the clinical follow-up CT (FCT) that is embedded in the treatment workflow after the fourth fraction. Results: ECT and clinical FCTs of 20 patients were compared to each other quantitatively in terms of absolute Hounsfield unit differences in the planning target volume (PTV) and in a convex hull (CH) enclosing the catheters. The median differences were 31.2 and 29.5 HU for the CH and the PTV, respectively. Conclusion: The proposed ECT approach was able to approximate the “anatomy of the day” and therefore, in principle, allows a dosimetric appraisal of the treatment plan quality before each fraction. In this way, it can contribute to a more detailed patient-specific quality assurance in iBT of the breast and help to identify the timing for a potential treatment adaptation.
CRIS-Team Scopus Importer:2023-08-25
Keywords: assurance; breast cancer; electromagnetic tracking; interstitial brachytherapy

Estimation of inter-fractional variations in interstitial multi-catheter breast brachytherapy using a hybrid treatment delivery system - Kallis, Karoline; Abu-Hossin, Nadin; Kreppner, Stephan; Lotter, Michael; Strnad, Vratislav; Fietkau, Rainer; Bert, Christoph (Radiotherapy and Oncology, 2019)
Purpose: Irradiation of the tumor bed using interstitial multi-catheter brachytherapy is one of the treatment options for breast cancer patients. In order to ensure the planned dose delivery an advanced quality intervention method using an electromagnetic tracking (EMT) system is presented. The system is used to assess inter-fractional variations within the framework of a patient study. Methods and materials: Until now 41 patients were included in the study for the evaluation and overall 355 EMT measurements were performed. The catheter traces are measured automatically and sequentially using an afterloader prototype (Flexitron, Elekta, Veenendaal, The Netherlands) equipped with an EMT sensor. The implant geometry is tracked directly after implantation, after CT imaging and after each irradiation fraction. The acquired data is rigidly registered to the catheter traces defined in the treatment plan and the dwell positions (DP) are reconstructed. DPs defined in treatment planning serve as reference. Breathing motion was corrected and recorded using three reference 6DoF sensors placed on the patients’ skin. The Euclidean distance between the planned and reconstructed DPs provides information about possible inter-fractional deviations. Further, the influence of various factors on the occurrence of large deviations was investigated, like the patients’ age, the length of the catheter, the breast volume, etc. Results: Over all patient measurements a median Euclidean distance of 2.19 mm was determined between the reconstructed DPs and the reference DPs. The median deviation combining all datasets was minimal (1.67 mm) at the measurement directly after CT imaging. The deviations between the different fractions have a median distance of 2.31 mm which could be improved to 2.05 mm by adapting the treatment plan according to the follow-up CT. No correlation between the distance to the skin, ribs, mammilla or the breast volume and the occurrences of large deviations was found. The largest deviations were determined in the upper inner quadrant of the breast. Conclusion: The afterloader prototype could be well integrated into the clinical routine and is beneficial for ensuring the quality of the brachytherapy. Overall, a small median DP deviation, lower than the used step size of 2.5 mm, was detected.
CRIS-Team Scopus Importer:2019-09-17
Keywords: Breast cancer; Electromagnetic tracking; Inter-fractional variations; Interstitial multi-catheter brachytherapy

Estimation of the α/β ratio of non-small cell lung cancer treated with stereotactic body radiotherapy - Klement, Rainer J.; Sonke, Jan Jakob; Allgäuer, Michael; Andratschke, Nicolaus; Appold, Steffen; Belderbos, José; Belka, C.; Dieckmann, K.; Eich, Hans T.; Flentje, Michael; Grills, Inga; Eble, Michael; et al. (Radiotherapy and Oncology, 2019)
Background: High-dose hypofractionated radiotherapy should theoretically result in a deviation from the typical linear-quadratic shape of the cell survival curve beyond a certain threshold dose, yet no evidence for this hypothesis has so far been found in clinical data of stereotactic body radiotherapy treatment (SBRT) for early-stage non-small cell lung cancer (NSCLC). A pragmatic explanation is a larger α/β ratio than the conventionally assumed 10 Gy. We here attempted an estimation of the α/β ratio for NSCLC treated with SBRT using individual patient data. Materials and methods: We combined two large retrospective datasets, yielding 1294 SBRTs (≤10 fractions) of early stage NSCLC. Cox proportional hazards regression, a logistic tumor control probability model and a biologically motivated Bayesian cure rate model were used to estimate the α/β ratio based on the observed number of local recurrences and accounting for tumor size. Results: A total of 109 local progressions were observed after a median of 17.7 months (range 0.6–76.3 months). Cox regression, logistic regression of 3 year tumor control probability and the cure rate model yielded best-fit estimates of α/β = 12.8 Gy, 14.9 Gy and 12–16 Gy (depending on the prior for α/β), respectively, although with large uncertainties that did not rule out the conventional α/β = 10 Gy. Conclusions: Clinicians can continue to use the simple LQ formalism to compare different SBRT treatment schedules for NSCLC. While α/β = 10 Gy is not ruled out by our data, larger values in the range 12–16 Gy are more probable, consistent with recent meta-regression analyses.
CRIS-Team Scopus Importer:2019-08-23
Keywords: Linear-quadratic model; NSCLC; Radiobiology; SBRT; Tumor control probability

ESTRO-ACROP guideline: Interstitial multi-catheter breast brachytherapy as Accelerated Partial Breast Irradiation alone or as boost - GEC-ESTRO Breast Cancer Working Group practical recommendations - Strnad, Vratislav; Major, Tibor; Polgar, Csaba; Lotter, Michael; Guinot, Jose-Luis; Gutierrez-Miguelez, Cristina; Galalae, Razvan; Van Limbergen, Erik; Guix, Benjamin; Niehoff, Peter; Loessl, Kristina; Hannoun-Levi, Jean-Michel (Radiotherapy and Oncology, 2018)
PURPOSE: This consensus statement from the Breast Cancer Working Group of Groupe Européen de Curiethérapie of European Society for Radiotherapy and Oncology (GEC-ESTRO) aims at generating practical guidelines for multi-catheter image-guided brachytherapy in the conservative management of breast cancer patients used for either Accelerated Partial Breast Irradiation (APBI) or for a breast boost. METHODS: Recent advances in techniques of multi-catheter brachytherapy were summarized and all the relevant literature was reviewed by a panel of experts. Panel members of the GEC-ESTRO experts participated in a series of conferences, supplemented their clinical experience, were surveyed to determine their current practices and patterns, performed a literature review, and formulated recommendations for implementing APBI with multi-catheter brachytherapy, focusing on treatment planning issues, catheter insertion, dosimetry and quality assurance. This document was reviewed and approved by the full panel, the GEC-ESTRO executive board and by the ACROP (Advisory Committee on Radiation Oncology Practice). RESULTS: Three-dimensional (3D) treatment planning, catheter insertion techniques, dosimetry and methods of quality assurance for APBI and boost with multi-catheter image-guided brachytherapy after breast conserving surgery are described. Detailed recommendations for daily practice including dose constraints are given. CONCLUSIONS: Recent standards and guidelines for the use of APBI with different multi-catheter image-guided brachytherapy techniques have been defined. Different techniques are used to insert the catheters. Guidelines are mandatory to assure precise catheter insertion for coverage of the target volume and to guarantee high-quality dosimetry. The same rules apply for brachytherapy based boost irradiation for breast cancer after whole breast irradiation as well as for partial breast re-irradiation.
EVALuna2:36533

ESTRO-ACROP guideline on surface guided radiation therapy - Freislederer, P.; Batista, V.; Ollers, M.; Buschmann, Martin; Steiner, E.; Kugele, M.; Fracchiolla, F.; Corradini, S.; De Smet, M.; Moura, F.; Perryck, S.; Dionisi, F.; et al. (Radiotherapy and Oncology, 2022)
Surface guidance systems enable patient positioning and motion monitoring without using ionising radiation. Surface Guided Radiation Therapy (SGRT) has therefore been widely adopted in radiation therapy in recent years, but guidelines on workflows and specific quality assurance (QA) are lacking. This ESTROACROP guideline aims to give recommendations concerning SGRT roles and responsibilities and highlights common challenges and potential errors. Comprehensive guidelines for procurement, acceptance, commissioning, and QA of SGRT systems installed on computed tomography (CT) simulators, C-arm linacs, closed-bore linacs, and particle therapy treatment systems are presented that will help move to a consensus among SGRT users and facilitate a safe and efficient implementation and clinical application of SGRT. (c) 2022 The Author(s). Published by Elsevier B.V. Radiotherapy and Oncology xxx (2022) xxx-xxx This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
CRIS-Team WoS Importer:2022-07-29

European Association of Urology Guidelines on Muscle-invasive and Metastatic Bladder Cancer: Summary of the 2023 Guidelines - Alfred Witjes, J.; Max Bruins, Harman; Carrión, Albert; Cathomas, Richard; Compérat, Eva; Efstathiou, Jason A.; Fietkau, Rainer; Gakis, Georgios; Lorch, Anja; Martini, Alberto; Mertens, Laura S.; Meijer, Richard P.; et al. (European Urology, 2023)
Context: We present an overview of the updated 2023 European Association of Urology (EAU) guidelines for muscle-invasive and metastatic bladder cancer (MMIBC). Objective: To provide practical evidence-based recommendations and consensus statements on the clinical management of MMIBC with a focus on diagnosis and treatment. Evidence acquisition: A broad and comprehensive scoping exercise covering all areas of the MMIBC guidelines has been performed annually since 2017. Searches cover the Medline, EMBASE, and Cochrane Libraries databases for yearly guideline updates. A level of evidence and strength of recommendation are assigned. The evidence cutoff date for the 2023 MIBC guidelines was May 4, 2022. Evidence synthesis: Patients should be counselled regarding risk factors for bladder cancer. Pathologists should describe tumour and lymph nodes in detail, including the presence of histological subtypes. The importance of the presence or absence of urothelial carcinoma (UC) in the prostatic urethra is emphasised. Magnetic resonance imaging (MRI) of the bladder is superior to computed tomography (CT) for disease staging, specifically in differentiating T1 from T2 disease, and may lead to a change in treatment approach in patients at high risk of an invasive tumour. Imaging of the upper urinary tract, lymph nodes, and distant metastasis is performed with CT or MRI; the additional value of flurodeoxyglucose positron emission tomography/CT still needs to be determined. Frail and comorbid patients should be evaluated by a multidisciplinary team. Postoperative histology remains the most important prognostic variable, while circulating tumour DNA appears to be an interesting predictive marker. Neoadjuvant systemic therapy remains cisplatin-based. In motivated and selected women and men, sexual organ–preserving cystectomy results in better functional outcomes without compromising oncological outcomes. Robotic and open cystectomy have comparable outcomes and should be combined with (extended) lymph node dissection. The diversion type is an individual choice after taking patient and tumour characteristics into account. Radical cystectomy remains a highly complex procedure with considerable morbidity and risk of mortality, although lower rates are observed for higher hospital volumes (>20 cases/yr). With proper patient selection, trimodal therapy (chemoradiation) has comparable outcomes to radical cystectomy. Adjuvant chemotherapy after surgery improves disease-specific survival and overall survival (OS) in patients with high-risk disease who did not receive neoadjuvant treatment, and is strongly recommended. There is a weak recommendation for adjuvant nivolumab, as OS data are not yet available. Health-related quality of life should be assessed using validated questionnaires at baseline and after treatment. Surveillance is needed to monitor for recurrent cancer and functional outcomes. Recurrences detected on follow-up seem to have better prognosis than symptomatic recurrences. Conclusions: This summary of the 2023 EAU guidelines provides updated information on the diagnosis and treatment of MMIBC for incorporation into clinical practice. Patient summary: The European Association of Urology guidelines panel on muscle-invasive and metastatic bladder cancer has released an updated version of the guideline containing information on diagnosis and treatment of this disease. Recommendations are based on studies published up to May 4, 2022. Surgical removal of the bladder and bladder preservation are discussed, as well as updates on the use of chemotherapy and immunotherapy in localised and metastatic disease.
CRIS-Team Scopus Importer:2023-10-27
Keywords: Bladder cancer; Evidenced-based; Guidelines; Metastatic; Muscle-invasive; Recommendations

Evaluating predictive modeling algorithms to assess patient eligibility for clinical trials from routine data - Köpcke, Felix; Lubgan, Dorota; Fietkau, Rainer; Scholler, Axel; Nau, Carla; Stürzl, Michael; Croner, Roland S.; Prokosch, Hans-Ulrich; Toddenroth, Dennis (BMC Medical Informatics and Decision Making, 2013)
Background: The necessity to translate eligibility criteria from free text into decision rules that are compatible with data from the electronic health record (EHR) constitutes the main challenge when developing and deploying clinical trial recruitment support systems. Recruitment decisions based on case-based reasoning, i.e. using past cases rather than explicit rules, could dispense with the need for translating eligibility criteria and could also be implemented largely independently from the terminology of the EHR's database. We evaluated the feasibility of predictive modeling to assess the eligibility of patients for clinical trials and report on a prototype's performance for different system configurations. Methods. The prototype worked by using existing basic patient data of manually assessed eligible and ineligible patients to induce prediction models. Performance was measured retrospectively for three clinical trials by plotting receiver operating characteristic curves and comparing the area under the curve (ROC-AUC) for different prediction algorithms, different sizes of the learning set and different numbers and aggregation levels of the patient attributes. Results: Random forests were generally among the best performing models with a maximum ROC-AUC of 0.81 (CI: 0.72-0.88) for trial A, 0.96 (CI: 0.95-0.97) for trial B and 0.99 (CI: 0.98-0.99) for trial C. The full potential of this algorithm was reached after learning from approximately 200 manually screened patients (eligible and ineligible). Neither block- nor category-level aggregation of diagnosis and procedure codes influenced the algorithms' performance substantially. Conclusions: Our results indicate that predictive modeling is a feasible approach to support patient recruitment into clinical trials. Its major advantages over the commonly applied rule-based systems are its independency from the concrete representation of eligibility criteria and EHR data and its potential for automation. © 2013 Köpcke et al.; licensee BioMed Central Ltd.
UnivIS-Import:2015-04-14:Pub.2013.tech.IMMD.infome.evalua_3

Evaluation of a dedicated Treatment Planning-MRI for Patients with cranial Stereotaxy - Grigo, Johanna; Masitho, Siti; Putz, Florian; Fietkau, Rainer; Bert, Christoph (STRAHLENTHERAPIE UND ONKOLOGIE, 2021)
CRIS-Team WoS Importer:2021-07-16

Evaluation of a high-resolution 3D T2-SPACE-FLAIR Sequence in Comparison to the conventional 2D T2-FLAIR Sequence for the Contouring of low malignant Tumor Parts in cerebral Gliomas - Siavooshhaghighi, H.; Mengling, Veit; Masitho, Siti; Filimonova, Irina; Mansoorian, S.; Weissmann, T.; Bert, Christoph; Fietkau, Rainer; Putz, Florian (STRAHLENTHERAPIE UND ONKOLOGIE, 2020)
CRIS-Team WoS Importer:2020-10-02

Evaluation of a Marker Clip System in Sonographically Guided Core Needle Biopsy for Breast Cancer Localization Before and After Neoadjuvant Chemotherapy - Schulz-Wendtland, Rüdiger; Dankerl, P.; Bani, Mayada; Fasching, Peter; Heusinger, K.; Lux, Michael P.; Jud, Sebastian; Rauh, C.; Bayer, C. M.; Schrauder, M. G.; Beckmann, Matthias; Uder, M.; et al. (Geburtshilfe und Frauenheilkunde, 2017)
Introduction The placement of intramammary marker clips has proven to be helpful for tumor localization in patients undergoing neoadjuvant chemotherapy and breast-conserving surgery. The purpose of our study was to investigate the feasibility of using a clip marker system for breast cancer localization and its influence on the imaging assessment of treatment responses after neoadjuvant chemotherapy. Patients and Methods Between March and June 2015, a total of 25 patients (n = 25), with a suspicion of invasive breast cancer with diameters of at least 2 cm (cT2), underwent preoperative sonographically guided core needle biopsy using a single-use breast biopsy system (HistoCore(TM)) and intramammary clip marking using a directly adapted clip system based on the established O-Twist Marker(TM), before their scheduled preoperative neoadjuvant chemotherapy. Localization of the intramammary marker clip was controlled by sonography and digital breast tomosynthesis. Results Sonography detected no dislocation of intrammammary marker clips in 20 of 25 patients (80 %), while digital breast tomosynthesis showed accurate placement without dislocation in 24 patients (96 %) (p < 0.05). There was no evidence of significant clip migration during preoperative follow-up imaging after neoadjuvant chemotherapy. No complication related to the clip marking was noted and there was no difficulty in evaluating the treatment response to neoadjuvant chemotherapy. Among the breast-conserving surgeries performed, no cases were identified in which intraoperative loss of the marker clip had occurred. Conclusion Our study underscores the importance of intramammary marking clip systems before neoadjuvant chemotherapy. Placement of marker clips is advised to facilitate accurate tumor bed localization. With regard to digital breast tomosynthesis, its development continues to improve the quality of diagnostics and the therapy of breast cancer particularly for small breast cancer tumors or in neoadjuvant chemotherapy setting.
EVALuna2:14620

Evaluation of a markerless SGRT-only workflow for breast cancer patients - Sauer, Tim-Oliver; Popp, D.; Ott, O. J.; Bert, Christoph (RADIOTHERAPY AND ONCOLOGY, 2021)
CRIS-Team WoS Importer:2021-11-26

Evaluation of Concomitant Systemic Treatment in Older Adults With Head and Neck Squamous Cell Carcinoma Undergoing Definitive Radiotherapy - Rühle, Alexander; Marschner, Sebastian; Haderlein, Marlen; Fabian, Alexander; Weymann, Maria; Behrens, Max; Senger, Carolin; Dickstein, Daniel R.; Kraft, Johannes; von der Grün, Jens; Chen, Eric; Aquino-Michaels, Todd; et al. (JAMA Network Open, 2023)
Importance: The number of older adults with head and neck squamous cell carcinoma (HNSCC) is increasing, and these patients are underrepresented in clinical trials. It is unclear whether the addition of chemotherapy or cetuximab to radiotherapy is associated with improved survival in older adults with HNSCC. Objective: To examine whether the addition of chemotherapy or cetuximab to definitive radiotherapy is associated with improved survival in patients with locoregionally advanced (LA) HNSCC. Design, Setting, and Participants: The Special Care Patterns for Elderly HNSCC Patients Undergoing Radiotherapy (SENIOR) study is an international, multicenter cohort study including older adults (≥65 years) with LA-HNSCCs of the oral cavity, oropharynx/hypopharynx, or larynx treated with definitive radiotherapy, either alone or with concomitant systemic treatment, between January 2005 and December 2019 at 12 academic centers in the US and Europe. Data analysis was conducted from June 4 to August 10, 2022. Interventions: All patients underwent definitive radiotherapy alone or with concomitant systemic treatment. Main Outcomes and Measures: The primary outcome was overall survival. Secondary outcomes included progression-free survival and locoregional failure rate. Results: Among the 1044 patients (734 men [70.3%]; median [IQR] age, 73 [69-78] years) included in this study, 234 patients (22.4%) were treated with radiotherapy alone and 810 patients (77.6%) received concomitant systemic treatment with chemotherapy (677 [64.8%]) or cetuximab (133 [12.7%]). Using inverse probability weighting to attribute for selection bias, chemoradiation was associated with longer overall survival than radiotherapy alone (hazard ratio [HR], 0.61; 95% CI, 0.48-0.77; P < .001), whereas cetuximab-based bioradiotherapy was not (HR, 0.94; 95% CI, 0.70-1.27; P = .70). Progression-free survival was also longer after the addition of chemotherapy (HR, 0.65; 95% CI, 0.52-0.81; P < .001), while the locoregional failure rate was not significantly different (subhazard ratio, 0.62; 95% CI, 0.30-1.26; P = .19). The survival benefit of the chemoradiation group was present in patients up to age 80 years (65-69 years: HR, 0.52; 95% CI, 0.33-0.82; 70-79 years: HR, 0.60; 95% CI, 0.43-0.85), but was absent in patients aged 80 years or older (HR, 0.89; 95% CI, 0.56-1.41). Conclusions and Relevance: In this cohort study of older adults with LA- HNSCC, chemoradiation, but not cetuximab-based bioradiotherapy, was associated with longer survival compared with radiotherapy alone.
CRIS-Team Scopus Importer:2023-03-10

Evaluation of finger A3 pulley rupture in the crimp grip position-a magnetic resonance imaging cadaver study - Bayer, Thomas; Adler, Werner; Schweizer, Andreas; Schoeffl, Isabelle; Uder, Michael; Janka, Rolf Matthias (Skeletal Radiology, 2015)
The correct diagnosis of an A3 pulley rupture is challenging for musculoskeletal radiologists. An A3 pulley rupture should in theory influence the shape of the proximal interphalangeal joint volar plate (VP) and the amount of bowstringing at level of the VP during finger flexion. The purpose of this study was to perform MRI with metric analysis of the VP configuration and VP bowstringing in cadaver fingers in the crimp grip position and to determine cut points for A3 pulley rupture.MRI in the crimp grip position was performed in 21 cadaver fingers with artificially created flexor tendon pulley tears (fingers with A3 pulley rupture n = 16, fingers without A3 pulley rupture n = 5). The distances of the translation of the VP relative to the middle phalanx base, the distances between the flexor tendons and the VP body, and the distances between the flexor tendon and bone (TB) were measured.Statistical analysis showed significantly lower VP translation distances and significantly higher VP tendon distances if the A3 pulley was ruptured. A2 TB and A4 TB distances did not differ significantly in specimens with and without A3 pulley rupture. The optimal cut points for A3 pulley rupture were a VP translation distance <2.8 mm and a VP tendon distance >1.4 mm.Reduction of the VP translation distance and augmentation of the VP tendon distance are suitable indirect signs of A3 pulley rupture.
EVALuna2:5492

Evaluation of newly adapted clip marker system in ultrasound-guided core needle biopsy for suspicion of breast cancer - Schulz-Wendtland, Rüdiger; Dankerl, Peter; Dilbat, G.; Bani, Mayada; Fasching, Peter; Heusinger, K.; Lux, Michael P.; Löhberg, Christian; Jud, Sebastian; Rauh, Claudia; Bayer, Christian M.; Beckmann, Matthias; et al. (Geburtshilfe und Frauenheilkunde, 2013)
Introduction: A newly adapted clip system for intramammary marking during ultrasound-guided core needle biopsy for suspicion of breast cancer is described and evaluated here. Material and Method: Fifty patients with suspicion of breast cancer (cT2) had ultrasound-guided core needle biopsy using a newly adapted clip marker system (HistoCore™ and O-Twist Marker™). Subsequently, ultrasound follow-up and tomosynthesis scans were done to determine the location of the marker clips. Results: No dislocation of the marker clip was detected on ultrasound in 45 of 50 patients (90%), and 5 patients (10%) had a maximum dislocation of 5 mm along the x-, y- or z-axis. Tomosynthesis scans demonstrated precise placement without dislocation of the clip markers in 48 patients (96%); 2 patients (4%) had a maximum dislocation of 3 mm along the x-, y- or z-axis. Conclusion: The newly developed clip marker system, a combination of a single-use breast biopsy needle and a precise, length-adapted intramammary marker clip, represents a further improvement in oncological therapy. This is of particular importance for patients requiring subsequent neoadjuvant chemotherapy, as in cases with complete tumour remission, there is no target point for preoperative, ultrasound-guided wire marking. © Georg Thieme Verlag KG Stuttgart New York.
CRIS-Team Scopus Importer:2023-03-08
Keywords: biopsy; breast; breast cancer; ultrasound

Evaluation of novice reader diagnostic performance in coronary CT angiography using an advanced cardiac software package - Dankerl, Peter; Hammon, Matthias; Tsymbal, Alexey; Achenbach, Stephan; Uder, Michael; Janka, Rolf Matthias; Cavallaro, Alexander Josef (International Journal of Computer Assisted Radiology and Surgery, 2014)
The purpose of this research was to evaluate whether a commercially available advanced cardiac software package for coronary CT angiography (CTA) interpretation may reliably assist inexperienced readers to screen for significant coronary artery stenoses.Coronary CTA data sets of 61 consecutive patients with suspected coronary artery disease were evaluated by three novice readers with no experience in cardiac CT interpretation. In the first 15 patients, the novice readers were trained to use the advanced cardiac software package (includes automatic detection of coronary vessels, curved MPR and VRT reconstructions and a measurement too) knowing the results of an expert read. In the next 46 patients, the novice readers had to state whether there is a significant coronary artery stenosis ([Formula: see text]50 %) and if they are confident with their diagnosis. The results of the novice readers were compared to the expert read.The 46 coronary CTA data sets contained 184 vessels with 15 stenoses in 9 patients. On a per-vessel analysis, novice reader 1/2/3 demonstrated 60 %/100 %/ 93% sensitivity, and 98 %/90 %/86 % specificity. Per patient, the readers diagnosed 36/28/29 cases correctly as free of stenoses, 6/9/8 correctly as having at least one stenosis, missed 3/0/1 cases with a stenosis and overdiagnosed 1/9/8 patients. Cohen's kappa values for the three readers versus the expert were 0.60, 0.61 and 0.54. The three novice readers felt confident in the diagnosis of 36/33/30 patients. In these patients, they missed one significant stenosis, showed a sensitivity of 100 %/100 %/75 % and a specificity of 100 %/92 %/88 %.The evaluated advanced cardiac software package successfully assists novice readers in interpreting coronary CTA data sets especially in ruling out significant coronary artery stenosis.
EVALuna2:11866

Evaluation of the influence of susceptibility-induced magnetic field distortions on the precision of contouring intracranial organs at risk for stereotactic radiosurgery - Mengling, Veit; Putz, Florian; Laun, Frederik Bernd; Perrin, Rosalind; Eisenhut, Felix; Dörfler, Arnd; Fietkau, Rainer; Bert, Christoph (Physics and Imaging in Radiation Oncology, 2020)
Background and purpose: Magnetic resonance imaging (MRI) is a crucial factor in optimal treatment planning for stereotactic radiosurgery. To further the awareness of possible errors in MRI, this work aimed to investigate the magnitude of susceptibility induced MRI distortions for intracranial organs at risk (OARs) and test the effectiveness of actively shimming these distortions. Materials and methods: Distortion maps for 45 exams of 42 patients (18 on a 1.5 T MRI scanner, 27 on a 3 T MRI scanner) were calculated based on a high-bandwidth double-echo gradient echo sequence. The investigated OARs were brainstem, chiasm, eyes, and optic nerves. The influence of active shimming was investigated by comparing unshimmed 1.5 T data with shimmed 3 T data and comparing the results to a model based prediction. Results: The median distortion for the different OARs was found to be between 0.13 and 0.18 mm for 1.5 T and between 0.11 and 0.13 mm for 3 T. The maximum distortion was found to be between 1.3 and 1.7 mm for 1.5 T and between 1.1 and 1.4 mm for 3 T. The variation of values was much higher for 1.5 T than for 3 T across all investigated OARs. Active shimming was found to reduce distortions by a factor of 2.3 to 2.9 compared to the expected values. Conclusions: Using a safety margin for OARs of 1 mm would have encompassed 99.8% of the distortions. Since distortions are inversely proportional to the readout bandwidth, they can be further reduced by increasing the bandwidth. Additional error sources like gradient nonlinearities need to be addressed separately.
CRIS-Team Scopus Importer:2020-08-21
Keywords: Brain; MRI; PRV; Safety margins; Stereotactic; Susceptibility artifacts

Evaluation of the role of remission status in a heterogeneous limited disease small-cell lung cancer patient cohort treated with definitive chemoradiotherapy - Manapov, Farkhad; Niyazi, Maximilian; Gerum, Sabine; Roengvoraphoj, Olarn; Eze, Chukwuka; Li, Minglun; Hildebrandt, Guido; Fietkau, Rainer; Klautke, Gunther; Belka, Claus (BMC Cancer, 2016)
The role of remission status in limited disease (LD) small-cell lung cancer (SCLC) patients treated with definitive chemoradiotherapy (CRT) remains to be finally clarified.Individual data from 184 patients treated with definitive CRT concurrently or sequentially were retrospectively reviewed. Kaplan-Meier analysis as well as univariate and multivariate Cox regression models were used to describe survival within patient subgroups defined by remission status.71 (39%) patients were treated in the concurrent, 113 (61%) in the sequential CRT mode. Prophylactic cranial irradiation (PCI) was applied in 71 (39%) patients. 37 (20%) patients developed local, while 89 (48%) distant recurrence. 58 (32%) patients developed metachronous brain metastases. Complete, partial remission and non-response (defined as stable and progressive disease) were documented in 65 (35%), 77 (42%), and 37 (20%) patients, respectively. In complete responders median overall survival was 21.8 months (95CI: 18.6 - 25) versus 14.9 (95% CI: 11.7 - 18.2) (p = 0.041, log-rank test) and 11.5 months (95% CI: 8.9 - 15.0) (p < 0.001, log-rank test) in partial and non-responders, respectively. The same effect was documented for the time to progression and distant metastasis-free survival. In the multivariate analysis achievement of complete remission as a variable shows a trend for the prolonged time to progression (p = 0.1, HR 1.48) and distant metastasis-free survival (p = 0.06, HR 1.63) compared to partial responders and was highly significant compared to non-responders.In this treated heterogeneous LD SCLC patient cohort complete remission was associated with longer time to progression, distant metastasis-free and overall survival compared to the non- and especially partial responders.
EVALuna2:18335

Evidence for improved survival with bevacizumab treatment in recurrent high-grade gliomas: a retrospective study with ("pseudo-randomized") treatment allocation by the health insurance provider - Hofmann, Susanne; Schmidt, Manuel; Weissmann, Thomas; Eyüpoglu, Ilker Yasin; Strnad, Annedore; Semrau, Sabine; Fietkau, Rainer; Putz, Florian; Lettmaier, Sebastian (Journal of Neuro-Oncology, 2020)
Introduction Despite a large number of trials, the role of bevacizumab (BEV) in the treatment of recurrent high-grade gliomas is still controversial. Evidence regarding an effect on overall survival in this context is ultimately inconclusive. At the Department of Radiation Oncology at Erlangen, Germany we treated a large cohort of patients with recurrent gliomas where bevacizumab use was determined exclusively by the health care provider's approval of reimbursement. Methods 61 patients (between 06/2008 and 01/2014) with recurrent high-grade gliomas had reimbursement requests for BEV sent to their health insurance. 37 patients out of 61 (60.7%) had their requests approved and therefore received bevacizumab (BEV-arm) as part of their treatment. The remaining 24 (39.3%) patients received standard therapy without bevacizumab (non-BEV-arm). Survival endpoints were defined with reference to the first BEV request to the health insurance provider. Results Median overall survival (OS) for the whole cohort was 7.0 months. OS was significantly better for BEV vs. Non-BEV patients (median, 10.3 vs. 4.2 months, logrank p = 0.023). There was an increased BEV benefit in cases of higher-order recurrences (first order recurrence BEV vs. Non-BEV, 12.5 vs. 10.2 months, p = 0.578) (second or higher order of recurrence, 9.9 vs. 2.6 months, p = 0.010). On multivariate analysis for overall survival the prognostic impact of bevacizumab (HR = 0.43, p = 0.034) remained significant. Conclusion Our results suggest an influence of BEV on overall survival in a heavily pretreated patient population suffering from high-grade gliomas with BEV benefit being greatest in case of second or later recurrence.
CRIS-Team WoS Importer:2020-05-29

Examination of a deformable motion model for respiratory movements and 4D dose calculations using different driving surrogates - Wölfelschneider, Jens; Seregni, Matteo; Fassi, Aurora; Ziegler, Marc; Baroni, Guido; Fietkau, Rainer; Riboldi, Marco; Bert, Christoph (Medical Physics, 2017)
PURPOSE: The aim of this study was to evaluate a surrogate-driven motion model based on four-dimensional computed tomography that is able to predict CT volumes corresponding to arbitrary respiratory phases. Furthermore, the comparison of three different driving surrogates is examined and the feasibility of using the model for 4D dose re-calculation will be discussed. METHODS: The study is based on repeated 4DCTs of twenty patients treated for bronchial carcinoma and metastasis. The motion model was estimated from the planning 4DCT through deformable image registration. To predict a certain phase of a follow-up 4DCT, the model considers inter-fractional variations (baseline correction) and intra-fractional respiratory parameters (amplitude and phase) derived from surrogates. The estimated volumes resulting from the model were compared to ground-truth clinical 4DCTs using absolute HU differences in the lung region and landmarks localized using the Scale Invariant Feature Transform. Finally, the γ-index was used to evaluate the dosimetric effects of the intensity differences measured between the estimated and the ground-truth CT volumes. RESULTS: The results show absolute HU differences between estimated and ground-truth images with median value (± standard deviation) of (61.3 ± 16.7) HU. Median 3D distances, measured on about 400 matching landmarks in each volume, were (2.9 ± 3.0) mm. 3D errors up to 28.2 mm were found for CT images with artifacts or reduced quality. Pass rates for all surrogate approaches were above 98.9% with a γ-criterion of 2%/2 mm. CONCLUSION: The results depend mainly on the image quality of the initial 4DCT and the deformable image registration. All investigated surrogates can be used to estimate follow-up 4DCT phases, however, uncertainties decrease for volumetric approaches. Application of the model for 4D dose calculations is feasible.
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Examination of Gold Marker Detection in Tracking Treatments of Liver Cancer Patients using Vero SBRT System - Ziegler, Marc; Brandt, Tobias; Lettmaier, S.; Strnad, Vratislav; Fietkau, Rainer; Bert, Christoph (2018)
EVALuna2:36476

Examination of the automatic fiducial marker detection on the Vero system - Ziegler, Marc; Brandt, Tobias; Lettmaier, S.; Fietkau, Rainer; Bert, Christoph (2018)
EVALuna2:36478

Exclusive endocrine therapy or partial breast irradiation for women aged ≥70years with luminal A-like early stage breast cancer (NCT04134598 – EUROPA): Proof of concept of a randomized controlled trial comparing health related quality of life by patient reported outcome measures - Meattini, Icro; Poortmans, Philip M.P.; Marrazzo, Livia; Desideri, Isacco; Brain, Etienne; Hamaker, Marije; Lambertini, Matteo; Miccinesi, Guido; Russell, Nicola; Saieva, Calogero; Strnad, Vratislav; Visani, Luca; et al. (Journal of Geriatric Oncology, 2021)
Background: Postoperative radiation therapy after breast conserving surgery in the older adult population is a matter of debate; although radiation therapy was shown to benefit these patients concerning local disease control, the absolute benefit was small and potentially negligible. Partial breast irradiation has been introduced as an alternative treatment approach for low-risk patients. Older adult patients with early breast cancer constitute a unique population with regards to prognosis and potential comorbidities, thus minimizing treatment to maintain health-related quality of life (HRQoL) without compromising survival is extremely important. Estimates of the patient's risk of benefit and/or harm with treatment should be performed together with an assessment of baseline comorbidities, life expectancy, and care preferences. Published data suggest that radiation therapy or endocrine therapy alone resulted in excellent disease control in older women with early breast cancer, and that the combination of both treatments has less incremental benefit than expected. Conversely, the toxicity profile of endocrine therapy is well known, often significantly impacting long term HRQoL of these potentially frail patients. Methods: Patients older than 70 years receiving breast conserving surgery with T1N0, Luminal A-like tumors will be randomized to receive partial breast irradiation-alone or endocrine therapy-alone. The main objectives are to determine patient reported outcome measures in terms of HRQoL, as assessed by the EORTC QLQ-C30 using the global health status of patients, and to demonstrate a non-inferior local control rate between arms. Secondary endpoints are represented by individual scales from QLQ-C30 and module QLQ-BR45 scores; ELD14 questionnaire; geriatric COre DatasEt assessment; distant control rate, adverse events rates, breast cancer specific, and overall survival. Discussion: The EUROPA trial is a new randomized trial focused on older adults (≥70 years) affected by good prognosis primary breast cancer. Our assumption is that postoperative radiation therapy-alone avoids the long-term toxicity of endocrine therapy and favorably impacts on HRQoL in this population. In the current report we present the trial's background and methods, focusing on perspectives in the field of precision medicine. Trial registration: The trial is registered with ClinicalTrial.gov Identifier NCT04134598 / EUROPA trial.
CRIS-Team Scopus Importer:2021-04-09
Keywords: Breast cancer; Endocrine therapy; Health-related quality of life; Older adult; Partial breast irradiation

Experience gained with Durvalumab Maintenance Therapy after definitive Chemoradiotherapy in Patients with NSCLC: Survival- and Toxicity Data from Routine clinical Practice - Lettmaier, S.; Hecht, Markus; Weissmann, Thomas; Fietkau, Rainer (STRAHLENTHERAPIE UND ONKOLOGIE, 2021)
CRIS-Team WoS Importer:2021-07-16

Experimental investigation of irregular motion impact on 4D PET-based particle therapy monitoring. - Tian, Y.; Stuetzer, K.; Enghardt, W.; Priegnitz, M.; Helmbrecht, S.; Bert, Christoph; Fiedler, F. (Physics in Medicine and Biology, 2016)
Particle therapy positron emission tomography (PT-PET) is an in vivo and non-invasive imaging technique to monitor treatment delivery in particle therapy. The inevitable patient respiratory motion during irradiation causes artefacts and inaccurate activity distribution in PET images. Four-dimensional (4D) maximum likelihood expectation maximisation (4D MLEM) allows for a compensation of these effects, but has up to now been restricted to regular motion for PT-PET investigations. However, intra-fractional motion during treatment might differ from that during acquisition of the 4D-planning CT (e.g. amplitude variation, baseline drift) and therefore might induce inaccurate 4D PET reconstruction results. This study investigates the impact of different irregular analytical one-dimensional (1D) motion patterns on PT-PET imaging by means of experiments with a radioactive source and irradiated moving phantoms. Three sorting methods, namely phase sorting, equal amplitude sorting and event-based amplitude sorting, were applied to manage the PET list-mode data. The influence of these sorting methods on the motion compensating algorithm has been analysed. The event-based amplitude sorting showed a superior performance and it is applicable for irregular motions with ?4 mm amplitude elongation and drift. For motion with 10 mm baseline drift, the normalised root mean square error was as high as 10.5% and a 10 mm range deviation was observed.
EVALuna2:18310

Expert consensus on re-irradiation for recurrent glioma - Krauze, Andra; Attia, Albert; Braunstein, Steve; Chan, Michael; Combs, Stephanie; Fietkau, Rainer; Fiveash, John; Flickinger, John; Grosu, Anca; Howard, Steven; Nieder, Carsten; Niyazi, Maximilian; et al. (Radiation Oncology, 2017)
PURPOSE: To investigate radiation oncologists' opinions on important considerations to offering re-irradiation (re-RT) as a treatment option for recurrent glioma. MATERIALS AND METHODS: A survey was conducted with 13 radiation oncologists involved in the care of central nervous system tumor patients. The survey was comprised of 49 questions divided into 2 domains: a demographic section (10 questions) and a case section (5 re-RT cases with 5 to 6 questions representing one or several re-RT treatment dilemmas as may be encountered in the clinic). Respondents were asked to rate the relevance of various factors to offering re-RT, respond to the cases with a decision to offer re-RT vs. not, volume to be treated, margins to be employed, dose/fractionation suggested and any additional comments with respect to rationale in each scenario. RESULTS: Sixty nine percent of responders have been practicing for greater than 10 years and 61% have re-RT 20 to 100 patients to date, with 54% seeing 2-5 re-RT cases per month and retreating 1-2 patients per month. Recurrent tumor volume, time since previous radiation therapy, previously administered dose to organs at risk and patient performance status were rated by the majority of responders (85%, 92%, 77%, and 69% respectively) as extremely relevant or very relevant to offering re-RT as an option. CONCLUSION: The experts' practice of re-RT is still heterogeneous, reflecting the paucity of high-quality prospective data available for decision-making. Nevertheless, practicing radiation oncologists can support own decisions by referring to the cases found suitable for re-RT in this survey.
EVALuna2:32866

Explainable convolutional neural networks for assessing head and neck cancer histopathology - Dörrich, Marion; Hecht, Markus; Fietkau, Rainer; Hartmann, Arndt; Iro, Heinrich; Gostian, Antoniu-Oreste; Eckstein, Markus; Kist, Andreas (Diagnostic Pathology, 2023)
Purpose: Although neural networks have shown remarkable performance in medical image analysis, their translation into clinical practice remains difficult due to their lack of interpretability. An emerging field that addresses this problem is Explainable AI. Methods: Here, we aimed to investigate the ability of Convolutional Neural Networks (CNNs) to classify head and neck cancer histopathology. To this end, we manually annotated 101 histopathological slides of locally advanced head and neck squamous cell carcinoma. We trained a CNN to classify tumor and non-tumor tissue, and another CNN to semantically segment four classes - tumor, non-tumor, non-specified tissue, and background. We applied Explainable AI techniques, namely Grad-CAM and HR-CAM, to both networks and explored important features that contributed to their decisions. Results: The classification network achieved an accuracy of 89.9% on previously unseen data. Our segmentation network achieved a class-averaged Intersection over Union score of 0.690, and 0.782 for tumor tissue in particular. Explainable AI methods demonstrated that both networks rely on features agreeing with the pathologist’s expert opinion. Conclusion: Our work suggests that CNNs can predict head and neck cancer with high accuracy. Especially if accompanied by visual explanations, CNNs seem promising for assisting pathologists in the assessment of cancer sections.
CRIS-Team Scopus Importer:2023-11-24
Keywords: Classification; Explainable AI; Head and neck cancer; Histopathology; Semantic segmentation

Exploring the Capabilities and Limitations of Large Language Models for Radiation Oncology Decision Support - Putz, Florian; Haderlein, Marlen; Lettmaier, Sebastian; Semrau, Sabine; Fietkau, Rainer; Huang, Yixing (International Journal of Radiation Oncology Biology Physics, 2024)
Keywords: Large language model; GPT-4; Radiation Oncology

Expression of Immune Phenotypes in Rectal Cancer after neoadjuvant Chemoradiotherapy - Schnellhardt, Sören; Hirneth, Johannes; Büttner-Herold, Maike; Daniel, Christoph; Fietkau, Rainer; Distel, Luitpold (STRAHLENTHERAPIE UND ONKOLOGIE, 2021)
CRIS-Team WoS Importer:2021-07-16

Extent of simultaneous radiation dose and iodine reduction at stable image quality in computed tomography of the chest: A systematic approach using automated tube voltage adaption and iterative reconstructions - Eller, Achim; Wüst, Wolfgang; Saake, Marc; Ellmann, Stephan; Kämmerer, Nadine; Hammon, Matthias; Janka, Rolf Matthias; Uder, Michael; May, Matthias (Medicine, 2018)
BACKGROUND: Aim of this study was to systematically combine tube voltage adaptation and iterative reconstructions for reduction of iodine and radiation dose. METHODS: Settings for the study protocol were evaluated in ex-ante trials to provide image quality that is comparable to a reference protocol at 120 kV with tube current modulation. Consecutive patients were randomized to undergo computed tomography (CT) of the chest using the study protocol (n = 62) or reference protocol (n = 50). Objective and subjective image quality was assessed and compared. RESULTS: Tube voltage was decreased to 100 kV in 47 patients and to 80 kV in 15 patients in the study group. The iodine dosage (16.1 vs 10.5 g) and the effective radiation dose (3.6 vs 2.5 mSv) were significantly decreased in the study group (both P < .001). Contrast-to-noise ratio was comparable in the pulmonary trunk and increased in the aorta (P < .01). Subjective image quality was comparable without statistically significance. CONCLUSIONS: Simultaneous reductions in iodine dosage and radiation dose by one-third are feasible for CT of the chest.
EVALuna2:34701

External Beam Accelerated Partial Breast Irradiation in Early Breast Cancer and the Risk for Radiogenic Pneumonitis - Ott, Oliver; Stillkrieg, Wilhelm; Lambrecht, Ulrike; Sauer, Tim-Oliver; Schweizer, Claudia; Lamrani, Allison; Strnad, Vratislav; Hack, Caroline; Beckmann, Matthias; Uder, Michael; Fietkau, Rainer; Distel, Luitpold (Cancers, 2022)
Simple Summary Accelerated partial breast irradiation represents a well-established and safe treatment alternative for selected patients with early stage breast cancer after breast-conserving surgery. In a prospective trial on external beam partial breast irradiation, the risk for radiogenic pneumonitis is analyzed. After a median follow-up of 56 (1-129) months, radiogenic pneumonitis grade 2 appeared in only 1/170 (0.6%) patients. Compared to standard whole breast irradiation, the radiation doses applied to the lungs were very low. The patient with the radiogenic pneumonitis was found to have a generally increased radiation susceptibility. Using accelerated partial breast irradiation, the risk of radiogenic pneumonitis appeared quite low and may be limited to very exceptional cases associated with innate risk factors with an increased radiation susceptibility. In order to evaluate the risk for radiation-associated symptomatic pneumonitis in a prospective external beam accelerated partial breast irradiation (APBI) trial, between 2011 and 2021, 170 patients with early stage breast cancer were enclosed in the trial. Patients were eligible for study participation if they had a histologically confirmed breast cancer or an exclusive ductal carcinoma in situ (DCIS), a tumor size <= 3 cm, free safety margins >= 2 mm, no involved axillary lymph nodes, tumor bed clips, and were >= 50 years old. Patients received APBI with 38 Gy with 10 fractions in 10 consecutive working days. The trial was registered at the German Clinical Trials Registry, DRKS-ID: DRKS00004417. Median follow-up was 56 (1-129) months. Ipsilateral lung MLD, V20, and V30 were 4.3 +/- 1.4 Gy, 3.0 +/- 2.0%, and 1.0 +/- 1.0%, respectively. Radiogenic pneumonitis grade 2 appeared in 1/170 (0.6%) patients two months after radiotherapy. Ipsilateral MLD, V20, and V30 were 6.1 Gy, 7, and 3% in this patient. Additionally, individual radiosensitivity was increased in this specific patient. Compared to WBI, APBI leads to lower lung doses. Using APBI, the risk of symptomatic radiogenic pneumonitis is very low and may be limited, with an ipsilateral V20 < 3% to very exceptional cases associated with innate risk factors with an increased radiation susceptibility.
CRIS-Team WoS Importer:2022-08-12

External-Beam-Accelerated Partial-Breast Irradiation Reduces Organ-at-Risk Doses Compared to Whole-Breast Irradiation after Breast-Conserving Surgery - Ott, Oliver; Stillkrieg, Willy; Lambrecht, Ulrike; Schweizer, Claudia; Lamrani, Allison; Sauer, Tim-Oliver; Strnad, Vratislav; Bert, Christoph; Hack, Carolin; Beckmann, Matthias; Fietkau, Rainer (Cancers, 2023)
In order to evaluate organ-at-risk (OAR) doses in external-beam-accelerated partial-breast irradiation (APBI) compared to standard whole-breast irradiation (WBI) after breast-conserving surgery. Between 2011 and 2021, 170 patients with early breast cancer received APBI within a prospective institutional single-arm trial. The prescribed dose to the planning treatment volume was 38 Gy in 10 fractions on 10 consecutive working days. OAR doses for the contralateral breast, the ipsilateral, contralateral, and whole lung, the whole heart, left ventricle (LV), and the left anterior descending coronary artery (LAD), and for the spinal cord and the skin were assessed and compared to a control group with real-world data from 116 patients who underwent WBI. The trial was registered at the German Clinical Trials Registry, DRKS-ID: DRKS00004417. Compared to WBI, APBI led to reduced OAR doses for the contralateral breast (0.4 ± 0.6 vs. 0.8 ± 0.9 Gy, p = 0.000), the ipsilateral (4.3 ± 1.4 vs. 9.2 ± 2.5 Gy, p = 0.000) and whole mean lung dose (2.5 ± 0.8 vs. 4.9 ± 1.5 Gy, p = 0.000), the mean heart dose (1.6 ± 1.6 vs. 1.7 ± 1.4 Gy, p = 0.007), the LV V23 (0.1 ± 0.4 vs. 1.4 ± 2.6%, p < 0.001), the mean LAD dose (2.5 ± 3.4 vs. 4.8 ± 5.5 Gy, p < 0.001), the maximum spinal cord dose (1.5 ± 1.1 vs. 4.5 ± 5.7 Gy, p = 0.016), and the maximum skin dose (39.6 ± 1.8 vs. 49.1 ± 5.8 Gy, p = 0.000). APBI should be recommended to suitable patients to minimize the risk of secondary tumor induction and the incidence of consecutive major cardiac events.
CRIS-Team Scopus Importer:2023-08-25
Keywords: accelerated partial-breast irradiation; breast cancer; mean heart dose; mean lung dose; organs-at-risk

Extracranial temporal bone paragangliomas: Re-defining the role of otologic surgery within the scope of function-preserving multimodal concepts - Mantsopoulos, Konstantinos; Thimsen, Vivian; Eisenhut, Felix; Weissmann, Thomas; Putz, Florian; Fietkau, Rainer; Iro, Heinrich; Hornung, Joachim; Taha, Lava (American Journal of Otolaryngology, 2022)
Introduction: The aim of this study was to present our concept in the management of extracranial temporal bone paragangliomas and demonstrate the outcome after primary surgical management of the middle ear component, with an individualized indication for adjuvant radiotherapy. Materials and methods: The records of all patients treated for extracranial jugulotympanic paragangliomas by means of primary surgical management between 2010 and 2021 were studied retrospectively. Results: Twenty-nine patients made up our study sample (mean age 58.8 years). 15 cases were managed solely by means of surgery. Out of the remaining 14 cases with reduction of the middle ear component, adjuvant irradiation was performed in 11 cases, whereas a wait-and-scan strategy was adopted at the patient's request in three cases. No further growth was detected in our study cases. Conclusion: Our protocol seems to be associated with an acceptable quality of life and a satisfactory oncologic outcome.
CRIS-Team WoS Importer:2021-10-15

Extramedullary plasmacytoma: Tumor occurrence and therapeutic concepts-A follow-up - Holler, Adrian; Cicha, Iwona; Eckstein, Markus; Haderlein, Marlen; Poettler, Marina; Rappl, Anja; Iro, Heinrich; Alexiou, Christoph (Cancer Medicine, 2022)
Background Extramedullary plasmacytoma (EMP) is a solitary tumor consisting of neoplastic plasma cells, with very little to no bone marrow involvement. EMPs are usually located in the head and neck region, but can also occur along the digestive tract, in lungs, or extremities. Methods Following our publication on EMP, which appeared in 1999 (Cancer 85:2305-14), we conducted a literature search for EMP-related reports published between 1999 and 2021. The documented cases, as well as 14 of our own patients from the ENT Clinic Erlangen, were extensively analyzed. Results Between 1998 and 2021, 1134 patients with EMP were reported, for whom information about the tumor localization was available. Among those, 62.4% had EMP in the head and neck area and 37.6% in other body regions. Data on therapy were reported in 897 patients, including 34.3% who received radiation, 28.1% surgery, 22.6% a combination of surgery and radiation, and 15.9% another therapy. In 76.9% patients no recurrence or transformation to multiple myeloma (MM) was reported, 12.8% showed local recurrence and 10.2% developed MM. Radiotherapy alone was associated with a tendency for increased occurrence of MM. In patients with EMP of head and neck area, combination therapy (surgery and radiation) resulted in a 5-year overall survival rate of 98.3%, surgery alone of 92.4%, and radiotherapy of 92.7%. Conclusions Collectively, our analyses indicate that surgical resection alone can achieve long-term tumor control in patients with EMP, if the tumor can be removed within safe limits without causing serious functional impairment. However, if this is not certain, either radiation or a combination of surgery and radiation therapy is suggested as an effective means of local tumor control.
CRIS-Team WoS Importer:2022-05-27
Keywords: extramedullary plasmacytoma; non-Hodgkin lymphoma; survival; therapy; tumor outcomes

Ex Vivo Apoptosis in CD8+ Lymphocytes Predicts Rectal Cancer Patient Outcome - Winkler, Sebastian; Hoppe, Philipp; Haderlein, Marlen; Hecht, Markus; Fietkau, Rainer; Distel, Luitpold (Gastroenterology Research and Practice, 2016)
Background. Apoptotic rates in peripheral blood lymphocytes can predict radiation induced normal tissue toxicity. We studied whether apoptosis in lymphocytes has a prognostic value for therapy outcome. Methods. Lymphocytes of 87 rectal cancer patients were ex vivo irradiated with 2 Gy, 8 Gy, or a combination of 2 Gy ionizing radiation and Oxaliplatin. Cells were stained with Annexin V and 7-Aminoactinomycin D and apoptotic and necrotic rates were analyzed by multicolor flow cytometry. Results. After treatment, apoptotic and necrotic rates in CD8+ cells are consistently higher than in CD4+ cells, with lower corresponding necrotic rates. Apoptotic and necrotic rates of CD4+ cells and CD8+ cells correlated well within the 2 Gy, 8 Gy, and 2 Gy and Oxaliplatin arrangements (p <= 0.009). High apoptotic CD8+ rates after 2 Gy, 8 Gy, and 2 Gy + Oxaliplatin treatment were prognostically favorable for metastasis-free survival (p = 0.009, p = 0.038, and p = 0.009) and disease-free survival (p = 0.013, p = 0.098, and p = 0.013). Conclusions. Ex vivo CD8+ apoptotic rates are able to predict the patient outcome in regard to metastasis-free or disease-free survival. Patients with higher CD8+ apoptotic rates in the peripheral blood have a more favorable prognosis. In addition to the prediction of late-toxicity by utilization of CD4+ apoptotic rates, the therapy outcome can be predicted by CD8+ apoptotic rates.
EVALuna2:18338

Ex Vivo Chromosomal Radiosensitivity Testing in Patients with Pathological Germline Variants in Breast Cancer High-Susceptibility Genes BReast CAncer 1 and BReast CAncer 2 - Zuhair Kassem, Tara; Wunderle, Marius; Kuhlmann, Lukas; Rübner, Matthias; Hübner, Hanna; Hoyer, Juliane; Reis, André; Fasching, Peter; Beckmann, Matthias; Hack, Carolin; Fietkau, Rainer; Distel, Luitpold (Current Issues in Molecular Biology, 2023)
Background: Individual radiosensitivity is an important factor in the occurrence of undesirable consequences of radiotherapy. The potential for increased radiosensitivity has been linked to highly penetrant heterozygous mutations in DNA repair genes such as BRCA1 and BRCA2. By studying the chromosomal radiosensitivity of BRCA1/2 mutation carriers compared to the general population, we study whether increased chromosomal radiation sensitivity is observed in patients with BRCA1/2 variants. Methods: Three-color-fluorescence in situ hybridization was performed on ex vivo-irradiated peripheral blood lymphocytes from 64 female patients with a heterozygous germline BRCA1 or BRCA2 mutation. Aberrations in chromosomes #1, #2 and #4 were analyzed. Mean breaks per metaphase (B/M) served as the parameter for chromosomal radiosensitivity. The results were compared with chromosomal radiosensitivity in a cohort of generally healthy individuals and patients with rectal cancer or breast cancer. Results: Patients with BRCA1/2 mutations (n = 64; B/M 0.47) overall showed a significantly higher chromosomal radiosensitivity than general healthy individuals (n = 211; B/M 0.41) and patients with rectal cancer (n = 379; B/M 0.44) and breast cancer (n = 147; B/M 0.45) without proven germline mutations. Chromosomal radiosensitivity varied depending on the locus of the BRCA1/2 mutation. Conclusions: BRCA1/2 mutations result in slightly increased chromosomal sensitivity to radiation. A few individual patients have a marked increase in radiation sensitivity. Therefore, these patients are at a higher risk for adverse therapeutic consequences.
CRIS-Team Scopus Importer:2023-09-08
Keywords: BRCA1; BRCA2; breast cancer; chromosomal radiosensitivity; FISH assay; radiation oncology; radiation sensitivity testing; radiotherapy

Ex vivo heat treatment of B16 melanoma and MCF-7 breast cancer cells by warm-water or microwave radiation in a closed-loop reactor - Hader, M.; Rosin, A.; Blank, T.; Wadepohl, M.; Gaipl, Udo; Frey, Benjamin (2018)
EVALuna2:36520

Ex vivo Hyperthermia of B16 Melanoma and MCF-7/MDA-MB-231 Breast Cancer Cells by Hot Water or Microwave Irradiation in a Circulatory Process - Hader, Michael; Rosin, A.; Gekle, S.; Wadepohl, M.; Fietkau, Rainer; Frey, Benjamin; Gaipl, Udo (STRAHLENTHERAPIE UND ONKOLOGIE, 2019)
CRIS-Team WoS Importer:2019-06-07

Ex vivo radiosensitivity is increased in non-cancer patients taking valproate - Stritzelberger, Jenny; Lainer, Jennifer; Gollwitzer, Stefanie; Graf, Wolfgang; Jost, Tina; Lang, Johannes; Müller, Tamara; Schwab, Stefan; Fietkau, Rainer; Hamer, Hajo; Distel, Luitpold (BMC Neurology, 2020)
Background: Valproate (VPA) is a commonly prescribed antiepileptic drug for patients experiencing epileptic seizures due to brain tumors. VPA increases radiation sensitivity in various tumor cells in vitro due to complex mechanisms. This could make tumors more vulnerable to ionizing radiation or overcome radioresistance. Yet, clinical data on possible improvement of tumor control by adding VPA to tumor therapy is controversial. Potentially radiosensitizing effects of VPA on healthy tissue remain unclear. To determine individual radiosensitivity, we analyzed blood samples of individuals taking VPA. Methods: Ex vivo irradiated blood samples of 31 adult individuals with epilepsy were studied using 3-color fluorescence in situ hybridization. Aberrations in chromosomes 1, 2 and 4 were analyzed. Radiosensitivity was determined by the mean breaks per metaphase (B/M) and compared to age-matched (2:1) healthy donors. Results: The patient cohort (n = 31; female: 38.7%) showed an increase of their average B/M value compared to healthy individuals (n = 61; female: 56.9%; B/M: 0.480 ± 0.09 vs. 0.415 ± 0.07; p =.001). The portion of radiosensitive (B/M > 0.500) and distinctly radiosensitive individuals (B/M > 0.600) was increased in the VPA group (54.9% vs. 11.3 and 9.7% vs. 0.0%; p <.001). In 3/31 patients, radiosensitivity was determined prior to and after VPA treatment and radiosensitivity was increased by VPA-treatment. Conclusions: In our study, we confirmed that patients treated with VPA had an increased radiosensitivity compared to the control group. This could be considered in patients taking VPA prior to the beginning of radiotherapy to avoid toxic side effects of VPA-treatment.
CRIS-Team Scopus Importer:2020-11-06
Keywords: 3-colour fluorescence-in-situ-hybridization; Breaks per metaphase; Individual radiosensitivity; Valproate

F18-FDG PET/CT imaging early predicts pathologic complete response to induction chemoimmunotherapy of locally advanced head and neck cancer: preliminary single-center analysis of the checkrad-cd8 trial - Beck, Michael; Hartwich, J.; Eckstein, Markus; Schmidt, D.; Gostian, Antoniu-Oreste; Müller-Hübner, Sarina; Rutzner, Sandra; Gaipl, Udo; Von Der Gruen, J.; Illmer, T.; Hautmann, M. G.; Klautke, G.; et al. (Annals of Nuclear Medicine, 2022)
Aim: In the CheckRad-CD8 trial patients with locally advanced head and neck squamous cell cancer are treated with a single cycle of induction chemo-immunotherapy (ICIT). Patients with pathological complete response (pCR) in the re-biopsy enter radioimmunotherapy. Our goal was to study the value of F-18-FDG PET/CT in the prediction of pCR after induction therapy. Methods: Patients treated within the CheckRad-CD8 trial that additionally received FDG- PET/CT imaging at the following two time points were included: 3–14 days before (pre-ICIT) and 21–28 days after (post-ICIT) receiving ICIT. Tracer uptake in primary tumors (PT) and suspicious cervical lymph nodes (LN +) was measured using different quantitative parameters on EANM Research Ltd (EARL) accredited PET reconstructions. In addition, mean FDG uptake levels in lymphatic and hematopoietic organs were examined. Percent decrease (Δ) in FDG uptake was calculated for all parameters. Biopsy of the PT post-ICIT acquired after FDG-PET/CT served as reference. The cohort was divided in patients with pCR and residual tumor (ReTu). Results: Thirty-one patients were included. In ROC analysis, ΔSUVmax PT performed best (AUC = 0.89) in predicting pCR (n = 17), with a decline of at least 60% (sensitivity, 0.77; specificity, 0.93). Residual SUVmax PT post-ICIT performed best in predicting ReTu (n = 14), at a cutpoint of 6.0 (AUC = 0.91; sensitivity, 0.86; specificity, 0.88). Combining two quantitative parameters (ΔSUVmax ≥ 50% and SUVmax PT post-ICIT ≤ 6.0) conferred a sensitivity of 0.81 and a specificity of 0.93 for determining pCR. Background activity in lymphatic organs or uptake in suspected cervical lymph node metastases lacked significant predictive value. Conclusion: FDG-PET/CT can identify patients with pCR after ICIT via residual FDG uptake levels in primary tumors and the related changes compared to baseline. FDG-uptake in LN + had no predictive value. Trial registry: ClinicalTrials.gov identifier: NCT03426657.
CRIS-Team Scopus Importer:2022-05-20
Keywords: FDG-PET/CT; Head neck cancer; HNSCC; Immunotherapy; Induction therapy

Factors influencing downstaging after neoadjuvant long-course chemoradiotherapy in rectal carcinoma - Kohl, Valerie; Weber, Klaus; Brunner, Maximilian; Geppert, Carol-Immanuel; Fietkau, Rainer; Grützmann, Robert; Semrau, Sabine; Merkel, Susanne (International Journal of Colorectal Disease, 2022)
Purpose This single-centre cohort study was designed to identify factors that can predict primary tumour downstaging by neoadjuvant chemoradiotherapy (nCRT) in rectal carcinoma. Methods Prospectively collected data from 555 patients with clinical T category (cT) cT3-4 rectal carcinoma treated between 1995 and 2019 were retrospectively analysed. All patients received long-term neoadjuvant chemoradiotherapy followed by surgery with curative intent at the Department of Surgery, University Hospital Erlangen, Germany. Patient-, tumour- and treatment-related factors with a potential impact on the downstaging of rectal carcinoma to pathological T category (pT) ≤ ypT2 and ypT0 were analysed in univariate and multivariate logistic regression analyses. The prognosis of patients with and without downstaging of the primary tumour was compared. Results A total of 288 (51.9%) patients showed downstaging to ≤ ypT2. Eighty-six (15.5%) patients achieved clinical complete regression (ypT0). In the multivariate logistic regression analysis, the factors cT category, BMI, ECOG score, CEA, histological type, extension in the rectum and year of the start of treatment were found to be independent factors for predicting downstaging to ≤ ypT2 after neoadjuvant chemoradiotherapy. The year of treatment initiation also remained an independent significant predictor for pathological complete regression. The prognosis was superior in patients with downstaging to ≤ ypT2 in terms of locoregional and distant recurrence as well as disease-free and overall survival. Conclusion Factors predicting downstaging after long-term nCRT could be identified. This may be helpful for counselling patients and selecting the optimal treatment for patients with advanced rectal carcinoma.
CRIS-Team WoS Importer:2022-05-27
Keywords: Rectal carcinoma; Neoadjuvant chemoradiotherapy; Downstaging; Tumour regression; Prediction of pathological response; Prognostic factors

Factors Influencing the Outcome of Head and Neck Cancer of Unknown Primary (HNCUP) - Rupp, Robin; Mantsopoulos, Konstantinos; Sievert, Matti; Gostian, Magdalena; Allner, Moritz; Grundtner, Philipp; Eckstein, Markus; Iro, Heinrich; Hecht, Markus; Gostian, Antoniu-Oreste; Balk, Matthias (Journal of Clinical Medicine, 2022)
Background: This study on patients with head and neck cancer of unknown primary (HNCUP) assesses the impact of surgical and non-surgical treatment modalities and the tumour biology on the oncological outcome. Methods: A total of 80 patients with HNCUP (UICC I-IV) were treated with simultaneous neck dissection followed by adjuvant therapy, between 1 January 2007 and 31 March 2020. As the primary objective, the influence of treatment modalities on the overall survival (OS), the disease-specific survival (DSS) and the progression-free survival (PFS) were analysed in terms of cox regression and recursive partitioning. The tumour biology served as secondary objectives. Results: The 5-year OS for the entire cohort was 67.7%, (95% CI: 54.2-81.2%), the 5-year DSS was 82.3% (72.1-92.5%) and the 5-year PFS was 72.8% (61.8-83.8%). Cox regression revealed that patients undergoing adjuvant radiotherapy only had a four times higher risk to die compared to patients receiving chemoradiation therapy (HR = 4.45 (1.40; 14.17), p = 0.012). The development of distant metastases had a significantly negative impact on OS (HR = 8.24 (3.21-21.15), p < 0.001) and DSS (HR = 23.79 (6.32-89.56), p < 0.001). Recursive portioning underlined the negative influence of distant metastases on OS (3.2-fold increase in death probability) and DSS (4.3-fold increase in death probability), while an UICC stage of IVb increased the risk for further progression of the disease by a factor of 2. Conclusions: The presence of distant metastases as well as adjuvant treatment with radiation without concomitant chemotherapy, were among others, significant predictors for the overall survival of HNCUP patients, with distant metastases being the most significant predictor.
CRIS-Team WoS Importer:2022-06-10

Fast optimization and dose calculation in scanned ion beam therapy - Hild, S.; Graeff, Christian; Trautmann, J.; Kraemer, M.; Zink, Klemens; Durante, Marco; Bert, Christoph (Medical Physics, 2014)
Particle therapy (PT) has advantages over photon irradiation on static tumors. An increased biological effectiveness and active target conformal dose shaping are strong arguments for PT. However, the sensitivity to changes of internal geometry complicates the use of PT for moving organs. In case of interfractionally moving objects adaptive radiotherapy (ART) concepts known from intensity modulated radiotherapy (IMRT) can be adopted for PT treatments. One ART strategy is to optimize a new treatment plan based on daily image data directly before a radiation fraction is delivered [treatment replanning (TRP)]. Optimizing treatment plans for PT using a scanned beam is a time consuming problem especially for particles other than protons where the biological effective dose has to be calculated. For the purpose of TRP, fast optimization and fast dose calculation have been implemented into the GSI in-house treatment planning system (TPS) TRiP98.This work reports about the outcome of a code analysis that resulted in optimization of the calculation processes as well as implementation of routines supporting parallel execution of the code. To benchmark the new features, the calculation time for therapy treatment planning has been studied.Compared to the original version of the TPS, calculation times for treatment planning (optimization and dose calculation) have been improved by a factor of 10 with code optimization. The parallelization of the TPS resulted in a speedup factor of 12 and 5.5 for the original version and the code optimized version, respectively. Hence the total speedup of the new implementation of the authors' TPS yielded speedup factors up to 55.The improved TPS is capable of completing treatment planning for ion beam therapy of a prostate irradiation considering organs at risk in this has been overseen in the review process. Also see below 6 min.
EVALuna2:18191

Fast SAR-Scans of Interstitial Microwave Dipole Antennas in a Muscle Equivalent Water Phantom - Erb, J.; Engelbrecht, Rainer; Schaller, Gerhard; Roos, D.; Seegenschmiedt, Heinrich; Fietkau, Rainer; Sauer, R. (41st Ann. Meeting of the Radiation Research Society and the 13th Annual Meeting of the North American Hyperthermia Society, 1993)
UnivIS-Import:2015-04-16:Pub.1993.tech.IE.LEH.fastsa

Favorable radiation field decrease in gastric marginal zone lymphoma Experience of the German Study Group on Gastrointestinal Lymphoma (DSGL) - Reinartz, Gabriele; Pyra, Regina P.; Lenz, Georg; Liersch, Rudiger; Stueben, Georg; Micke, Oliver; Willborn, Kay; Hess, Clemens F.; Probst, Andreas; Fietkau, Rainer; Jany, Ralf; Schultze, Juergen; et al. (Strahlentherapie und Onkologie, 2019)
Purpose Long-term impact of stage-adapted field reduction in a large cohort of gastric marginal zone lymphoma (gMZL) patients treated conservatively with curative radiation therapy (RT).
CRIS-Team WoS Importer:2019-06-07

Feasibility of a 12-month-exercise intervention during and after radiation and chemotherapy in cancer patients: impact on quality of life, peak oxygen consumption, and body composition - Grabenbauer, Alexander; Grabenbauer, Andrea J.; Lengenfelder, Rosa; Grabenbauer, Gerhard G.; Distel, Luitpold (Radiation Oncology, 2016)
Accumulating evidence suggests that exercise is effective in treating many of the acute and chronic side effects of anti-cancer therapy. A recent meta-analysis supported the use of exercise to prevent or treat fatigue and lymphoedema and to improve functional status in breast cancer patients.This trial was intended as a controlled, prospective feasibility study evaluating the impact of physical exercise (PE) in cancer patients during and after treatment with radio- and chemotherapy. Inclusion criteria were previous or ongoing treatment for cancer, motivation for PE of 0.5-1hour duration at least twice weekly for at least 3 months. Continuation of PE was encouraged thereafter. Every three months the following endpoints were assessed: Peak oxygen consumption as measured by supervised cardiopulmonary exercise test, body composition and quality of life.A total of 45 patients were included with a median age of 49 years. Forty were female and five male. Cancer types were: Breast cancer (n = 30/67 %), gastrointestinal cancer (n = 5/12 %), other types (n = 10/22 %). Thirty-eight (84 %) of the patients were included during curative treatment of their disease. Seven (16 %) were considered palliative. Adherence to the PE-programme longer than 6 months was noted for 41/45 (91 %) of the patients. Intensity of PE was thrice weekly in 32/45 (71 %), twice weekly in 11/45 (24 %). Two of 45 patients (5 %) had no PE. Mean peak oxygen consumption increased from 18.8 ± 5.6 ml/min/kg to 20.5 ± 3 ml/min/kg and 19.9 ± 4.7 ml/min/kg at 3 months (p = 0.005) and 12 months (p = 0.003), respectively. Median fat mass decreased from 30.7 ± 15 kg to 28.9 ± 15 kg and 29.5 ± 13 kg at 3 months (p = 0.001) and 12 months (p = 0.017), respectively. Global health status scores increased from a median baseline value of 54.9 ± 16.3 to 66.4 ± 14 % and 68.0 ± 20.3 % at 3 months (p = 0.001) and 12 months (p = 0.002), respectively.This exercise programme in cancer patients with 2-3 weekly supervised sessions over three months was well feasible and demonstrated measurable improvement of oxygen consumption, body composition and quality of life. In addition, a 90 %-adherence rate to the PE-programme beyond 6 months was encouraging. Further randomized prospective data in a larger patient population will be collected comparing the impact of two versus four months supervision.
EVALuna2:18344

Feasibility of artificial-intelligence-based synthetic computed tomography in a magnetic resonance-only radiotherapy workflow for brain radiotherapy: Two-way dose validation and 2D/2D kV-image-based positioning - Masitho, Siti; Szkitsak, Juliane; Grigo, Johanna; Fietkau, Rainer; Putz, Florian; Bert, Christoph (Physics and Imaging in Radiation Oncology, 2022)
Background and purpose: Magnetic Resonance Imaging (MRI)-only workflow eliminates the MRI-computed tomography (CT) registration inaccuracy, which degrades radiotherapy (RT) treatment accuracy. For an MRI-only workflow MRI sequences need to be converted to synthetic-CT (sCT). The purpose of this study was to evaluate a commercially available artificial intelligence (AI)-based sCT generation for dose calculation and 2D/2D kV-image daily positioning for brain RT workflow. Materials and methods: T1-VIBE DIXON was acquired at the 1.5 T MRI for 26 patients in RT setup for sCTs generation. For each patient, a volumetric modulated arc therapy (VMAT) plan was optimized on the CT, then recalculated on the sCT; and vice versa. sCT-based digitally reconstructed radiographs (DRRs) were fused with stereoscopic X-ray images recorded as image guidance for clinical treatments. Dosimetric differences between planned/recalculated doses and the differences between the calculated and recorded clinical couch shift/rotation were evaluated. Results: Mean ΔD50 between planned/recalculated doses for target volumes ranged between −0.2 % and 0.2 %; mean ΔD50 and ΔD0.01ccm were −0.6 % and 1.6 % and −1.4 % and 1.0 % for organ-at-risks, respectively. Differences were tested for clinical equivalence using intervals ±2 % (dose), ±1mm (translation), and ±1° (rotation). Dose equivalence was found using ±2 % interval (p < 0.001). The median differences between lat./long./vert. couch shift between CT-based/sCT-based DRRs were 0.3 mm/0.2 mm/0.3 mm (p < 0.05); median differences between lat./long./vert. couch rotation were −1.5°/0.1°/0.1° (after improvement of RT setup: −0.4°/−0.1°/−0.4°, p < 0.05). Conclusions: This in-silico study showed that the AI-based sCT provided equivalent results to the CT for dose calculation and daily stereoscopic X-ray positioning when using an optimal RT setup during MRI acquisition.
CRIS-Team Scopus Importer:2022-11-25
Keywords: Artificial intelligence; Brain radiotherapy; kV-image-based positioning; MRI-only workflow; Synthetic CT

Feasibility of daily kV-Recording-based Positioning by using DRRs from an AI-based synthetic CT for MR-only intracranial Stereotactic Radiotherapy - Masitho, Siti; Grigo, Johanna; Szkitsak, Juliane; Reissig, L.; Fietkau, Rainer; Putz, Florian; Bert, Christoph (STRAHLENTHERAPIE UND ONKOLOGIE, 2022)
CRIS-Team WoS Importer:2022-06-03

Feasibility of Respiratory-gated High-pitch Spiral CT:: Free-breathing Inspiratory Image Quality - Lell, Michael; Scharf, Michael; Eller, Achim; Wüst, Wolfgang; Allmendinger, Thomas; Fuchs, Florian; Achenbach, Stephan; Uder, Michael; May, Matthias (Academic Radiology, 2016)
This study aimed to develop and implement a respiratory-gated setup for dual-source computed tomography (CT) at high pitch to examine patients in a reproducible inspiratory phase.Twenty-one patients underwent free-breathing respiratory-gated chest CT using a high-pitch scan mode no more than 6 months after inspiratory breath-held nongated CT, which serves as reference. Scan parameters were as follows: pitch = 3.4, 128 × 0.6 mm collimation, 0.28 s gantry rotation time, and 150 ref.mAs per tube at 120 kV. The examinations were triggered using the tidal wave provided by a respiratory-gating system as input signal. Image quality was assessed focusing on artifacts and delineation of the anatomical and pathological structures. Lung volumes were measured on both free-breathing and reference examinations.All examinations were performed without complications. Image quality was high with both protocols. Significantly less motion artifacts were recorded with the high-pitch mode compared to the reference (P = 0.02). Most of the artifacts were located in the peripheral parts of the lower lobes for the study group and in the central part of the left lower lobe for the reference. Average total lung volume was 4.5 ± 1.5 L in respiratory-gated examinations and 5.8 ± 0.9 L in examinations with breath-hold in inspiration.High-pitch chest CT scanning during free breathing minimizes motion artifacts, improving image quality in patients with limited breath-holding abilities. To assure scanning in an inspiratory phase, data acquisition should be triggered with a respiratory-gating system.
EVALuna2:12027

Feasibility Study on Cardiac Arrhythmia Ablation Using High-Energy Heavy Ion Beams - Lehmann, H. Immo; Graeff, Christian; Simoniello, Palma; Constantinescu, Anna; Takami, Mitsuru; Lugenbiel, Patrick; Richter, Daniel; Eichhorn, Anna; Prall, Matthias; Kaderka, Robert; Fiedler, Fine; Helmbrecht, Stephan; et al. (Scientific Reports, 2016)
High-energy ion beams are successfully used in cancer therapy and precisely deliver high doses of ionizing radiation to small deep-seated target volumes. A similar noninvasive treatment modality for cardiac arrhythmias was tested here. This study used high-energy carbon ions for ablation of cardiac tissue in pigs. Doses of 25, 40, and 55 Gy were applied in forced-breath-hold to the atrioventricular junction, left atrial pulmonary vein junction, and freewall left ventricle of intact animals. Procedural success was tracked by (1.) in-beam positron-emission tomography (PET) imaging; (2.) intracardiac voltage mapping with visible lesion on ultrasound; (3.) lesion outcomes in pathohistolgy. High doses (40-55 Gy) caused slowing and interruption of cardiac impulse propagation. Target fibrosis was the main mediator of the ablation effect. In irradiated tissue, apoptosis was present after 3, but not 6 months. Our study shows feasibility to use high-energy ion beams for creation of cardiac lesions that chronically interrupt cardiac conduction.
EVALuna2:33045

FEN1 Inhibition as a Potential Novel Targeted Therapy against Breast Cancer and the Prognostic Relevance of FEN1 - Berfelde, Johanna; Hildebrand, Laura; Kuhlmann, Lukas; Fietkau, Rainer; Distel, Luitpold (International Journal of Molecular Sciences, 2024)
To improve breast cancer treatment and to enable new strategies for therapeutic resistance, therapeutic targets are constantly being studied. Potential targets are proteins of DNA repair and replication and genomic integrity, such as Flap Endonuclease 1 (FEN1). This study investigated the effects of FEN1 inhibitor FEN1-IN-4 in combination with ionizing radiation on cell death, clonogenic survival, the cell cycle, senescence, doubling time, DNA double-strand breaks and micronuclei in breast cancer cells, breast cells and healthy skin fibroblasts. Furthermore, the variation in the baseline FEN1 level and its influence on treatment prognosis was investigated. The cell lines show specific response patterns in the aspects studied and have heterogeneous baseline FEN1 levels. FEN1-IN-4 has cytotoxic, cytostatic and radiosensitizing effects, expressed through increasing cell death by apoptosis and necrosis, G2M share, senescence, double-strand breaks and a reduced survival fraction. Nevertheless, some cells are less affected by the cytotoxicity and fibroblasts show a rather limited response. In vivo, high FEN1 mRNA expression worsens the prognosis of breast cancer patients. Due to the increased expression in breast cancer tissue, FEN1 could represent a new tumor and prognosis marker and FEN1-IN-4 may serve as a new potent agent in personalized medicine and targeted breast cancer therapy.
CRIS-Team Scopus Importer:2024-03-08
Keywords: apoptosis; breast cancer cell lines; FEN1; FEN1 inhibition; FEN1-IN-4; ionizing radiation; necrosis; radiosensitivity; targeted therapy; TNBC

Fibroblast-like Synoviocytes show Gender and Inflammatory Status-specific Responses on the Treatment with low-dose X-ray Therapy - Deloch, Lisa; Rueckert, M.; Piltz, M.; Fietkau, Rainer; Frey, Benjamin; Gaipl, Udo (STRAHLENTHERAPIE UND ONKOLOGIE, 2020)
CRIS-Team WoS Importer:2020-10-02

Fine needle aspiration cytology of lymph nodes in breast cancer follow-up is a feasible alternative to watchful waiting and to histology - Hammon, Matthias; Dankerl, Peter; Janka, Rolf Matthias; Wachter, David; Hartmann, Arndt; Schulz-Wendtland, Rüdiger; Uder, Michael; Wenkel, Evelyn (BMC Women's Health, 2015)
Early detection of loco-regional breast cancer recurrence improves patients' overall survival, as treatment can be initiated or active treatment can be changed. If a suspicious lymph node is diagnosed during a follow-up exam, surgical excision is often performed. The aim of this study was to evaluate the diagnostic performance of the minor invasive ultrasound-guided fine-needle aspiration cytology (FNAC) in sonomorphologically suspicious lymph nodes in breast cancer follow-up.Between April 2010 and November 2012, we performed ultrasound-guided FNAC in 38 sonographically suspicious lymph nodes of 37 breast cancer follow-up patients. Cytological specimens were evaluated if the sample material was sufficient for diagnosis and if they contained cancer cells. Patients with negative cytology were followed up clinically and sonographically. To evaluate the diagnostic performance we calculated sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for physical examination, the different sonomorphological malignancy criteria and FNAC.In 36/38 (94.7 %) lymph nodes, the pathologist had enough material to establish a final diagnosis; in 2/38 (5.3 %) lymph nodes, the probe material was non-evaluable during cytology, these 2 were excluded from further statistical evaluation. Cytology revealed malignancy in 21 lymph nodes and showed no evidence for malignancy in 15 lymph nodes. There was no evidence for malignant disease in follow-up exams in the 15 cytologically benign lymph nodes with an average follow-up time of 3 years. The diagnostic performances of physical examination and FNAC were: Sensitivity 52/100 %, specificity 88/100 %, PPV 85/100 %, NPV 60/100 %, respectively.Our preliminary results show that FNAC is a safe and fast diagnostic approach for the evaluation of suspicious lymph nodes in the follow-up of patients with breast cancer and, thus, together with follow-up represents a feasible alternative to surgery.
EVALuna2:6744

First clinical evaluation of breathing controlled four-dimensional computed tomography imaging - Szkitsak, Juliane; Werner, René; Fernolendt, Susanne; Schwarz, Annette; Ott, Oliver; Fietkau, Rainer; Hofmann, Christian; Bert, Christoph (Physics and Imaging in Radiation Oncology, 2021)
Background and Purpose: Four-dimensional computed tomography (4DCT) has become an essential part of radiotherapy planning but is often affected by artifacts. A new breathing controlled 4DCT (i4DCT) algorithm has been introduced. This study aims to present the first clinical data and to evaluate the achieved image quality, projection data coverage and beam-on time. Material & Methods: The analysis included i4DCT data for 129 scans of patients with thoracic tumors. Projection data coverage and beam-on time were evaluated. Additionally, image quality was exemplarily discussed and rated by ten clinical experts with a 5-score-scale for 30 patients with large variations in their breathing pattern (‘challenging subgroup’). Rated images were reconstructed amplitude- and phase-based. Results: Expert scoring revealed that 78% (amplitude-based) and 63% (phase-based) of the challenging subgroup were artifact-free (rating ≥4). For the entire cohort, average beam-on time per couch position was 4.9 ± 1.6 s. For the challenging subgroup, time increased slightly but not significantly compared to the remaining patients (5.1 s vs. 4.9 s; p = 0.64). Median projection data coverage was 93% and 94% for inhalation and exhalation, respectively, for the entire cohort. The comparison for the subgroup and the remaining patients revealed a small but significant decrease of the median coverage values for the challenging cases (inhalation: 90% vs. 94%, p = 0.02; exhalation: 93% vs. 94%, p = 0.02). Conclusions: This first clinical evaluation of i4DCT shows very promising results in terms of image quality and projection data coverage. The results agree with and support the results of previous i4DCT phantom studies.
CRIS-Team Scopus Importer:2021-11-12
Keywords: 4DCT; Motion artifacts; Respiratory motion

First clinical experience with a novel, mobile cone-beam CT system for treatment quality assurance in brachytherapy - Karius, Andre; Strnad, Vratislav; Lotter, Michael; Kreppner, Stephan; Bert, Christoph (Strahlentherapie und Onkologie, 2022)
Background and purpose: On-site cone-beam computed tomography (CBCT) has gained in importance in adaptive brachytherapy during recent years. Besides treatment planning, there is increased need particularly for image-guidance during interventional procedures and for image-guided treatment quality assurance (QA). For this purpose, an innovative CBCT device was rolled out at our hospital as the first site worldwide. We present the first clinical images and experiences. Materials and methods: The novel CBCT system is constructed of a 121 cm diameter ring gantry, and features a 43.2 × 43.2 cm2 flat-panel detector, wireless remote-control via tablet-PC, and battery-powered maneuverability. Within the first months of clinical operation, we performed CBCT-based treatment QA for a total of 26 patients (8 with breast, 16 with cervix, and 2 with vaginal cancer). CBCT scans were analyzed regarding potential movements of implanted applicators in-situ during the brachytherapy course. Results: With the presented device, treatment QA was feasible for the majority of patients. The CBCT scans of breast patients showed sufficient contrast between implanted catheters and tissue. For gynecologic patients, a distinct visualization of applicators was achieved in general. However, reasonable differentiations of organic soft tissues were not feasible. Conclusion: The CBCT system allowed basic treatment QA measures for breast and gynecologic patients. For image-guidance during interventional brachytherapy procedures, the current image quality is not adequate. Substantial performance enhancements are required for intraoperative image-guidance.
CRIS-Team Scopus Importer:2022-03-18
Keywords: Adaptive brachytherapy; Gynecologic brachytherapy; Image-guidance; Mobile imaging; On-site computed tomography imaging

First Erlang Experience with Durvalumab Maintenance Therapy after definitive Radiochemotherapy in Patients with NSCLC - Lettmaier, S.; Hecht, Markus; Fietkau, Rainer (STRAHLENTHERAPIE UND ONKOLOGIE, 2019)
CRIS-Team WoS Importer:2019-06-07

First Steps Toward Ultrasound-Based Motion Compensation for Imaging and Therapy: Calibration with an Optical System and 4D PET Imaging - Schwaab, Julia; Kurz, Christopher; Sarti, Cristina; Bongers, Andre; Schoenahl, Frederic; Bert, Christoph; Debus, Juergen; Parodi, Katia; Jenne, Juergen Walter (Frontiers in Oncology, 2015)
Target motion, particularly in the abdomen, due to respiration or patient movement is still a challenge in many diagnostic and therapeutic processes. Hence, methods to detect and compensate this motion are required. Diagnostic ultrasound (US) represents a non-invasive and dose-free alternative to fluoroscopy, providing more information about internal target motion than respiration belt or optical tracking. The goal of this project is to develop an US-based motion tracking for real-time motion correction in radiation therapy and diagnostic imaging, notably in 4D positron emission tomography (PET). In this work, a workflow is established to enable the transformation of US tracking data to the coordinates of the treatment delivery or imaging system - even if the US probe is moving due to respiration. It is shown that the US tracking signal is equally adequate for 4D PET image reconstruction as the clinically used respiration belt and provides additional opportunities in this concern. Furthermore, it is demonstrated that the US probe being within the PET field of view generally has no relevant influence on the image quality. The accuracy and precision of all the steps in the calibration workflow for US tracking-based 4D PET imaging are found to be in an acceptable range for clinical implementation. Eventually, we show in vitro that an US-based motion tracking in absolute room coordinates with a moving US transducer is feasible.
EVALuna2:18367