Profound survival benefit with concurrent chemotherapy: insights from a Chinese phase III trial in older patients with esophageal cancer - Schweizer, Claudia; Fietkau, Rainer; Putz, Florian (Strahlentherapie und Onkologie, 2022)
CRIS-Team WoS Importer:2022-04-01

Prognostic and predictive value of PD-L1 expression and tumour infiltrating lymphocytes (TiLs) in locally advanced NSCLC treated with simultaneous radiochemotherapy in the randomized, multicenter, phase III German Intergroup lung Trial (GILT) - Tufman, Amanda; Neumann, Jens; Manapov, Farkhad; Sellmer, Laura; Jung, Andreas; Kauffmann-Guerrero, Diego; Kahnert, Kathrin; Mertsch, Pontus; Borgmeier, Astrid; Semrau, Sabine; Rittmeyer, Achim; Ulm, Bernhard; et al. (Lung Cancer, 2021)
Objectives: Immune checkpoint inhibition after radiochemotherapy (RTCT) has become a new standard of care for locally advanced non-small cell lung cancer with programmed death-ligand 1 (PD-L1) expression. However, little is known about the prognostic role of immune response markers in this setting. We analysed PD-L1 expression and tumour infiltrating lymphocytes (TiLs) in tumour biopsies from the multicenter German Intergroup Lung Trial (GILT), which previously randomised patients with stage III NSCLC to RTCT with or without consolidation chemotherapy. Materials and methods: We retrospectively analyzed tumour biopsies from patients treated in the GILT trial. PD-L1 expression was analysed using the Ventana SP263 assay and TiL score (low, intermediate, high) and pattern (excluded, inflamed, desert) were assessed. The primary endpoint of the biomarker analysis was PFS in patients with PD-L1 ≥ 1% vs. PD-L1 < 1% NSCLC. Secondary endpoints explored the prognostic relevance of additional PD-L1 expression levels and TiL score and pattern. Results: Biopsies were available from 92 patients treated with RTCT. Patients with available tumor tissue did not differ significantly from the whole study population. PD-L1 scores from 78 samples were available for analysis. There was no difference in PFS in the PD-L1 < 1% vs. PD-L1 ≥ 1% subgroups. TiL score was available in 66 patients. Patients with high TiL score showed favourable overall survival compared to the low TiL subgroup. This trend was most pronounced in those patients treated with consolidative chemotherapy. Conclusion: In this analysis, PD-L1 expression did not correlate with PFS following RTCT. However, patients with TiLs > 10% were found to have longer overall survival, especially for those patients treated with consolidation chemotherapy after the end of RTCT. Further analyses to explore the prognostic and predictive relevance of TiLs in the context of consolidative checkpoint inhibition with durvalumab are required.
CRIS-Team Scopus Importer:2021-09-17
Keywords: Checkpoint inhibition; Chemoradiotherapy; PDL1; Prognostic factors; TiLs

Prognostic impact of gross tumor volume during radical radiochemotherapy of locally advanced non-small cell lung cancer-results from the NCT03055715 multicenter cohort study of the Young DEGRO Trial Group - Ostheimer, C.; Maeurer, M.; Ebert, N.; Schmitt, D.; Krug, D.; Baumann, R.; Henkenberens, C.; Giordano, F. A.; Sautter, L.; Lopez, Guerra; Fleischmann, D. F.; Niyazi, M.; et al. (Strahlentherapie und Onkologie, 2021)
Background In radical radiochemotherapy (RCT) of inoperable non-small-cell lung cancer (NSCLC) typical prognostic factors include T- and N-stage, while there are still conflicting data on the prognostic relevance of gross tumor volume (GTV) and particularly its changes during RCT. The NCT03055715 study of the Young DEGRO working group of the German Society of Radiation Oncology (DEGRO) evaluated the prognostic impact of GTV and its changes during RCT.
CRIS-Team WoS Importer:2021-01-22

Prognostic Importance of the CD8-based Immune Status Inflamed, immune-Excluded, and immune Desert in Head and Neck Cancer Patients can be further subdivided by regulatory T Cells - Echarti, A.; Hecht, Markus; Fietkau, Rainer; Distel, Luitpold (STRAHLENTHERAPIE UND ONKOLOGIE, 2019)
CRIS-Team WoS Importer:2019-06-07

Prognostic role of patient gender in limited-disease small-cell lung cancer treated with chemoradiotherapy - Roengvoraphoj, Olarn; Eze, Chukwuka; Niyazi, Maximilian; Li, Minglun; Hildebrandt, Guido; Fietkau, Rainer; Belka, Claus; Manapov, Farkhad (Strahlentherapie und Onkologie, 2017)
BACKGROUND: Previous studies have demonstrated that female gender could be a prognostic factor in limited-disease (LD) small-cell lung cancer (SCLC), but the correlation between patient gender and survival parameters remains unclear. PATIENTS AND METHODS: Data from 179 LD SCLC patients treated with definitive chemoradiotherapy (CRT) were reviewed. Influence of patient gender on time to progression (TTP), local control (LC), brain metastasis-free (BMFS), distant metastasis-free (DMFS) and overall survival (OS) was analysed. RESULTS: Definitive CRT was completed by 179 (110 men/69 women) patients. Of these, 68 (38%; 34 men/34 women) patients were treated in concurrent and 111 (62%; 76 men/35 women) in sequential mode. Prophylactic cranial irradiation (PCI) was subsequently applied in 70 (39%; 36 men/34 women) patients with partial or complete response after CRT. Median OS was 20 (95% confidence interval [CI] 10-22) and 14 (95% CI 10-18) months in female and male patients, respectively (p = 0.021). In subgroups defined by remission status (complete and partial response) after CRT, an OS benefit for females compared to males was also detected. There was no correlation between patient gender and TTP, LC or DMFS, and no difference in OS in the female and male subgroups treated with PCI. The incidence of metachronous brain metastases (BMs) in the male and female subgroups differed significantly (40/110 men vs. 18/69 women, p = 0.03). Also, mean BMFS was significantly longer in women (p = 0.023). Patient gender also significantly correlated with OS on multivariate analysis after adjustment for other prognostic factors (p = 0.04, HR 1.38, 95% CI 1.08-1.92). CONCLUSION: In this heterogeneous LD SCLC patient cohort treated with definitive CRT, female gender was significantly associated with longer BMFS and OS, as well as with a lower incidence of metachronous brain failure.
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Prognostic Significance of CD8-Based Immune Status Inflamed, Immune-Excluded and Immune Desert in Head and Neck Tumors can be Further Subdivided by Regulatory T Cells - Distel, Luitpold; Echarti, Alessia; Fietkau, Rainer; Hecht, Markus (ONCOLOGY RESEARCH AND TREATMENT, 2020)
CRIS-Team WoS Importer:2020-03-20

Prognostic Significance of immune-associated Side Effects under Radioimmunotherapy and Immunotherapy alone in Patients of the prospective ST-ICI Study - Schweizer, C.; Schubert, P.; Haderlein, Marlen; Rutzner, Sandra; Semrau, Sabine; Donaubauer, Anna-Jasmina; Becker, Ina; Frey, Benjamin; Fietkau, Rainer; Gaipl, Udo; Hecht, Markus (STRAHLENTHERAPIE UND ONKOLOGIE, 2020)
CRIS-Team WoS Importer:2020-10-02

Prognostic subdivision of ypT3 rectal tumours according to extension beyond the muscularis propria - Merkel, Susanne; Weber, K.; Schellerer, Vera; Göhl, Jonas; Fietkau, Rainer; Agaimy, Abbas; Hohenberger, Werner; Hermanek, Peter (British Journal of Surgery, 2014)
The subdivision of T3 in rectal carcinoma according to the depth of invasion into perirectal fat has been recommended in the TNM Supplement since 1993. This study assessed the prognostic impact of this pathological staging in tumours removed after neoadjuvant chemoradiotherapy (ypT3).Data from patients with ypT3 rectal carcinoma (less than 12 cm from the anal verge) treated with neoadjuvant chemoradiation and total mesorectal excision were analysed. Tumour category ypT3 was subdivided into ypT3a (5 mm or less) and ypT3b (more than 5 mm), based on histological measurements of maximal tumour invasion beyond the outer border of the muscularis propria.Important differences between ypT3a (81 patients) and ypT3b (43) were found in 5-year rates of locoregional recurrence (7 versus 18 per cent; P = 0·049), distant metastasis (20 versus 41 per cent; P = 0·002), disease-free survival (73 versus 47 per cent; P = 0·001), overall survival (79 versus 74 per cent; P = 0·036) and cancer-related survival (81 versus 74 per cent; P = 0·007). In Cox regression analyses, the ypT3 subclassification was identified as an independent prognostic factor for disease-free (ypT3b: hazard ratio (HR) 2·13, 95 per cent confidence interval 1·16 to 3·89; P = 0·014), observed (ypT3b: HR 2·02, 1·05 to 3·87; P = 0·035) and cancer-related (ypT3b: HR 2·46, 1·20 to 5·04; P = 0·014) survival. Extramural venous invasion was found to be an additional prognostic factor, but the pathological node category after chemoradiotherapy (ypN) did not influence survival.In ypT3 rectal carcinomas, the proposed subclassification is superior to ypN in predicting prognosis.
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Prognostic Value of Homotypic Cell Internalization by Nonprofessional Phagocytic Cancer Cells - Schwegler, Manuela; Wirsing, Anna Maria; Schenker, Hannah; Ott, Laura; Ries, Johannes; Buettner-Herold, Maike; Fietkau, Rainer; Putz, Florian; Distel, Luitpold (BioMed Research International, 2015)
Background. In this study, we investigated the prognostic role of homotypic tumor cell cannibalism in different cancer types. Methods. The phenomenon of one cell being internalized into another, which we refer to as "cell-in-cell event," was assessed in 416 cases from five head and neck cancer cohorts, as well as one anal and one rectal cancer cohort. The samples were processed into tissue microarrays and immunohistochemically stained for E-cadherin and cleaved caspase-3 to visualize cell membranes and apoptotic cell death. Results. Cell-in-cell events were found in all of the cohorts. The frequency ranged from 0.7 to 17.3 cell-in-cell events per mm(2). Hardly any apoptotic cells were found within the cell-in-cell structures, although apoptotic cell rates were about 1.6 to two times as high as cell-in-cell rates of the same tissue sample. High numbers of cell-in-cell events showed adverse effects on patients' survival in the head and neck and in the rectal cancer cohorts. In multivariate analysis, high frequency was an adverse prognostic factor for overall survival in patients with head and neck cancer (p = 0.008). Conclusion. Cell-in-cell events were found to predict patient outcomes in various types of cancer better than apoptosis and proliferation and might therefore be used to guide treatment strategies.
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Progress Patterns under Radioimmunotherapy - clinical Evaluation of the prospective STICI Study - Schubert, Philipp; Schweizer, Claudia; Roesch, Johannes; Haderlein, Marlen; Rutzner, Sandra; Semrau, Sabine; Donaubauer, Anna-Jasmina; Zhou, Jianguo; Frey, Benjamin; Fietkau, Rainer; Gaipl, Udo; Hecht, Markus (STRAHLENTHERAPIE UND ONKOLOGIE, 2021)
CRIS-Team WoS Importer:2021-07-16

Proliferating non-professional Phagocytes are able to generate Cell-in-Cell Structures - Hofmann, Andrea; Seeberg, J.; Fietkau, Rainer; Distel, Luitpold (2018)
EVALuna2:36485

Proliferating non-professional Phagocytes to generate Cell-in-Cell Structures - Hofmann, Andrea; Fietkau, Rainer; Distel, Luitpold (STRAHLENTHERAPIE UND ONKOLOGIE, 2021)
CRIS-Team WoS Importer:2021-07-16

Prolonged high-pressure treatments in mammalian skeletal muscle result in loss of functional sodium channels and altered calcium channel kinetics. - Friedrich, Oliver; Kress, Kai; Hartmann, Martin; Frey, Benjamin; Sommer, Karl; Ludwig, Horst; Fink, Rainer (Cell Biochemistry and Biophysics, 2006)
Activation and inactivation of ion channels involve volume changes from conformational rearrangements of channel proteins. These volume changes are highly susceptible to changes in ambient pressure. Depending on the pressure level, channel function may be irreversibly altered by pressure. The corresponding structural changes persist through the post-decompression phase. High-pressure applications are a useful tool to evaluate the pressure dependence as well as pressure limits for reversibility of such alterations. Mammalian cells are only able to tolerate much lower pressures than microorganisms. Although some limits for pressure tolerance in mammalian cells have been evaluated, the mechanisms of pressure-induced alteration of membrane physiology, in particular of channel function, are unknown. To address this question, we recorded fast inward sodium (I(Na)) and slowly activating L-type calcium (I(Ca)) currents in single mammalian muscle fibers in the post-decompression phase after a prolonged 3-h, high-pressure treatment of up to 20 MPa. I(Na) and I(Ca) peak amplitudes were markedly reduced after pressure treatment at 20 MPa. This was not from a general breakdown of membrane integrity as judged from in situ high-pressure fluorescence microscopy. Membrane integrity was preserved even for pressures as high as 35 MPa at least for pressure applications of shorter durations. Therefore, the underlying mechanisms for the observed amplitude reductions have to be determined from the activation (time-to-peak [TTP]) and inactivation (tau(dec)) kinetics of I(Na) and I(Ca). No major changes in I(Na) kinetics, but marked increases, both in TTP and tau(dec) for I(Ca), were detected after 20 MPa. The apparent molecular volume changes (activation volumes) deltaV(double dagger) for the pressure-dependent irreversible alteration of channel gating approached zero for Na+ channels. For Ca2+ channels, deltaV(double dagger) was very large, with approx 2.5-fold greater values for channel activation than inactivation (approx 210 A3). We conclude, that in skeletal muscle, high pressure differentially and irreversibly affects the gating properties and the density of functional Na+ and Ca2+ channels. Based on these results, a model of high pressure-induced alterations to the channel conformation is proposed.

Proposal for a new M1 subclassification in colorectal carcinoma - Merkel, Susanne; Weber, K.; Croner, R.; Golcher, H.; Göhl, Jonas; Agaimy, Abbas; Semrau, S.; Wein, Axel; Hohenberger, Werner; Wittekind, C.; Siebler, Jürgen (2016)
EVALuna2:2176

Prospective Assessment of the Inflammation Parameters in Blood Counts and Blood Serum as prognostic/predictive Parameters for Treatment with Immune Checkpoint-Inhibitors - Schweizer, Claudia; Haderlein, Marlen; Schubert, Philipp; Zhou, Jianguo; Semrau, Sabine; Rutzner, Sandra; Gostian, Antoniu-Oreste; Frey, Benjamin; Donaubauer, Anna-Jasmina; Eckstein, Markus; Becker, Ina; Fietkau, Rainer; et al. (STRAHLENTHERAPIE UND ONKOLOGIE, 2021)
CRIS-Team WoS Importer:2021-07-16

Prospective development and validation of a liquid immune profile-based signature (LIPS) to predict response of patients with recurrent/metastatic cancer to immune checkpoint inhibitors - Zhou, Jianguo; Donaubauer, Anna-Jasmina; Frey, Benjamin; Becker, Ina; Rutzner, Sandra; Eckstein, Markus; Sun, Roger; Ma, Hu; Schubert, Philipp; Schweizer, Claudia; Fietkau, Rainer; Deutsch, Eric; et al. (Journal for ImmunoTherapy of Cancer, 2021)
Background The predictive power of novel biological markers for treatment response to immune checkpoint inhibitors (ICI) is still not satisfactory for the majority of patients with cancer. One should identify valid predictive markers in the peripheral blood, as this is easily available before and during treatment. The current interim analysis of patients of the ST-ICI cohort therefore focuses on the development and validation of a liquid immune profile-based signature (LIPS) to predict response of patients with metastatic cancer to ICI targeting the programmed cell death protein 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) axis. Methods A total of 104 patients were prospectively enrolled. 54 immune cell subsets were prospectively analyzed in patients' peripheral blood by multicolor flow cytometry before treatment with ICI (pre-ICI; n=89), and after the first application of ICI (n=65). Pre-ICI, patients were randomly allocated to a training (n=56) and a validation cohort (n=33). Univariate Cox proportional hazards regression analysis and least absolute shrinkage and selection operator Cox model were used to create a predictive immune signature, which was also checked after the first ICI, to consider the dynamics of changes in the immune status. Results Whole blood samples were provided by 89 patients pre-ICI and by 65 patients after the first ICI. We identified a LIPS which is based on five immune cell subtypes: CD14 high monocytes, CD8+/PD-1 + T cells, plasmacytoid dendritic cells, neutrophils, and CD3 + /CD56 + /CD16 + natural killer (NK)T cells. The signature achieved a high accuracy (C-index 0.74 vs 0.71) for predicting overall survival (OS) benefit in both the training and the validation cohort. In both cohorts, the low-risk group had significantly longer OS than the high-risk group (HR 0.26, 95% CI 0.12 to 0.56, p=0.00025; HR 0.30, 95% CI 0.10 to 0.91, p=0.024, respectively). Regarding the whole cohort, LIPS also predicted progression-free survival (PFS). The identified LIPS was not affected by clinicopathological features with the exception of brain metastases. NKT cells and neutrophils of the LIPS can be used as dynamic predictive biomarkers for OS and PFS after first administration of the ICI. Conclusion Our study identified a predictive LIPS for survival of patients with cancer treated with PD-1/PD-L1 ICI, which is based on immune cell subsets in the peripheral whole blood. Trial registration number NCT03453892.
CRIS-Team Scopus Importer:2021-03-05
Keywords: biomarkers; immunotherapy; programmed cell death 1 receptor; tumor; tumor biomarkers; tumor microenvironment

Prospective Evaluation of All-lesion Versus Single-lesion Radiotherapy in Combination With PD-1/PD-L1 Immune Checkpoint Inhibitors - Schubert, Philipp; Rutzner, Sandra; Eckstein, Markus; Frey, Benjamin; Schweizer, Claudia; Haderlein, Marlen; Lettmaier, Sebastian; Semrau, Sabine; Gostian, Antoniu Oreste; Zhou, Jianguo; Gaipl, Udo; Fietkau, Rainer; et al. (Frontiers in Oncology, 2020)
Background: Local ablative treatments improve survival in patients with oligometastatic disease in addition to chemotherapy. The application of immune checkpoint inhibitors prolonged patients’ survival in different tumor entities. This raises the question if patients still benefit from intensified local treatments in combination with a more efficient systemic treatment with immune checkpoint inhibitors. Methods: The prospective non-interventional ST-ICI trial investigates treatment with PD-1/PD-L1 (Programmed cell death protein 1/Programmed cell death 1 ligand 1) immune checkpoint inhibitors and radiotherapy in different tumor entities. Patients who started radiotherapy and immunotherapy concomitantly were included in this interim analysis. In this cohort patients with all-lesion radiotherapy (all tumor lesions irradiated, al-RT) were compared to patients with radiotherapy to only a single of their tumor lesions (single-lesion radiotherapy, sl-RT). Endpoints of the interim analysis were progression-free survival (PFS), overall survival (OS) and time to progression (TTP). Results: A total of 104 patients were registered between April 2017 and August 2019. Fifty patients started immune checkpoint inhibitor treatment and radiotherapy concomitantly and were included. Most frequent tumor entities were non-small cell lung cancer (62%) followed by head and neck squamous cell cancer (26%). Most frequent location of radiotherapy was lung (34%) and central nervous system (20%). Median duration of follow-up was 8.6 months beginning with first administration of the immune-checkpoint-inhibitor. Median PFS was 9.2 months (95% CI, 5.8 – 12.6) in the al-RT group and 3.0 months (95% CI, 2.5 – 3.5) in the sl-RT group (p<0.001). Median OS was 11.6 months (95% CI, 8.1 - 15.1) in the al-RT group and 4.2 months (95% CI, 3.0 - 5.4) in the sl-RT group (p=0.007). Median TTP was not reached in the al-RT group compared to 4.6 months (95% CI, 1.1–8.0) in the sl-RT group (p=0.028). Univariate Cox regression analyses computed tumor entity, histology, central nervous system metastases, immunotherapy drug and al-RT as predictors of OS (with an effect p-value of ≤ 0.1). In the multivariable analysis only tumor entity and al-RT remained prognostic factors for OS. Conclusion: Patients with PD-1/PD-L1 immune checkpoint inhibitor therapy benefit from local radiotherapy to all known lesions compared to single-lesion radiotherapy regarding PFS and OS.
CRIS-Team Scopus Importer:2020-11-20
Keywords: all-lesion; immune checkpoint inhibitors; immunotherapy; oligometastatic; radiotherapy; single-lesion

Prospective Evaluation of CD45RA+/CCR7- Effector Memory T (TEMRA) Cell Subsets in Patients with Primary and Secondary Brain Tumors during Radiotherapy of the Brain within the Scope of the Prospective Glio-CMV-01 Clinical Trial - Scheer, Ilka; Becker, Ina; Schmitter, Charlotte; Semrau, Sabine; Fietkau, Rainer; Gaipl, Udo; Frey, Benjamin; Donaubauer, Anna-Jasmina (Cells, 2023)
Radiotherapy (RT) of the brain is a common treatment for patients with high-grade gliomas and brain metastases. It has previously been shown that reactivation of cytomegalovirus (CMV) frequently occurs during RT of the brain. This causes neurological decline, demands antiviral treatment, and is associated with a worse prognosis. CMV-specific T cells are characterized by a differentiated effector memory phenotype and CD45RA+ CCR7- effector memory T (TEMRA) cells were shown to be enriched in CMV seropositive individuals. In this study, we investigated the distribution of TEMRA cells and their subsets in the peripheral blood of healthy donors and, for the first time, prospectively within the scope of the prospective Glio-CMV-01 clinical trial of patients with high-grade glioma and brain metastases during radiation therapy as a potential predictive marker. First, we developed a multicolor flow cytometry-based assay to monitor the frequency and distribution of TEMRA cells in a longitudinal manner. The CMV serostatus and age were considered as influencing factors. We revealed that patients who had a reactivation of CMV have significantly higher amounts of CD8+ TEMRA cells. Further, the distribution of the subsets of TEMRA cells based on the expression of CD27, CD28, and CD57 is highly dependent on the CMV serostatus. We conclude that the percentage of CD8+ TEMRA cells out of all CD8+ T cells has the potential to serve as a biomarker for predicting the risk of CMV reactivation during RT of the brain. Furthermore, this study highlights the importance of taking the CMV serostatus into account when analyzing TEMRA cells and their subsets.
CRIS-Team Scopus Importer:2023-03-17
Keywords: brain metastases; cytomegalovirus (CMV); glioblastoma; infection; radiotherapy; T

Prospective evaluation of the prognostic value of immune-related adverse events in patients with non-melanoma solid tumour treated with PD-1/PD-L1 inhibitors alone and in combination with radiotherapy - Schweizer, Claudia; Schubert, Philipp; Rutzner, Sandra; Eckstein, Markus; Haderlein, Marlen; Lettmaier, Sebastian; Semrau, Sabine; Gostian, Antoniu Oreste; Frey, Benjamin; Gaipl, Udo; Zhou, Jianguo; Fietkau, Rainer; et al. (European Journal of Cancer, 2020)
Background: Prospective data about the prognostic value of immune-related adverse events (irAEs) in non-melanoma solid tumours are rare. The prognostic value of irAEs in patients treated with combined radiotherapy and immunotherapy is currently unknown. Patients and methods: The prospective non-interventional ST-ICI trial investigates treatment response of tumour patients to anti–programmed cell death-ligand 1 (PD-L1) immune checkpoint inhibitors alone and in combination with radiotherapy and possible predictive markers. Patients undergoing immunotherapy or immunoradiotherapy were surveyed for irAEs. Results: A total of 104 patients were included of whom 29 patients (28%) developed irAEs. Additional radiotherapy was performed in 50 patients (48%). Main tumour entities within the entire cohort were non–small cell lung cancer (NSCLC) (44%) and head and neck squamous cell carcinoma (42%). The rate of irAEs did not differ in patients with and without radiotherapy (p = 0.668). Patients who developed irAEs had longer overall survival (OS) (median: 22.8 months versus 9.0 months without irAEs, p = 0.001) and progression-free survival (PFS) (median: 7.8 months versus 3.2 months without irAEs, p = 0.002). In the subgroup with combined radiotherapy, patients with irAEs also had longer OS (median: 22.8 months versus 7.1 months without irAEs, p = 0.005) and PFS (median: 8.8 months versus 3.0 months without irAEs, p = 0.005). On multivariate analysis only PD-L1 on tumour cells (p = 0.049) and irAEs (p = 0.001) remained independent predictors of OS. Conclusion: The development of irAEs represents a favourable prognostic parameter in patients undergoing immunotherapy and immunoradiotherapy for solid tumours.
CRIS-Team Scopus Importer:2020-10-16
Keywords: Immune checkpoint inhibitors; Immune-related adverse events; Non-melanoma solid tumours; Prognostic parameters; Radiotherapy

Protein Supplementation to Augment the Effects of High Intensity Resistance Training in Untrained Middle-Aged Males: The Randomized Controlled PUSH Trial - Wittke, Andreas; von Stengel, Simon; Hettchen, Michael; Froehlich, Michael; Giessing, Juergen; Lell, Michael; Scharf, Michael; Bebenek, Michael; Kohl, Matthias; Kemmler, Wolfgang (BioMed Research International, 2017)
High intensity (resistance exercise) training (HIT) defined as a "single set resistance exercise to muscular failure" is an efficient exercise method that allows people with low time budgets to realize an adequate training stimulus. Although there is an ongoing discussion, recent meta-analysis suggests the significant superiority of multiple set (MST) methods for body composition and strength parameters. The aim of this study is to determine whether additional protein supplementation may increase the effect of a HIT-protocol on body composition and strength to an equal MST-level. One hundred and twenty untrained males 30-50 years old were randomly allocated to three groups: (a) HIT, (b) HIT and protein supplementation (HIT&P), and (c) waiting-control (CG) and (after cross-over) high volume/high-intensity-training (HVHIT). HIT was defined as "single set to failure protocol" while HVHIT consistently applied two equal sets. Protein supplementation provided an overall intake of 1.5-1.7 g/kg/d/body mass. Primary study endpoint was lean body mass (LBM). LBM significantly improved in all exercise groups (p <= 0.043); however only HIT&P and HVHIT differ significantly from control (p <= 0.002). HIT diverges significantly from HIT&P (p = 0.017) and nonsignificantly from HVHIT (p = 0.059), while no differences were observed for HIT&P versus HVHIT (p = 0.691). In conclusion, moderate to high protein supplementation significantly increases the effects of a HIT-protocol on LBM in middle-aged untrained males.
EVALuna2:14638

Pt-Fe3O4, Pd-Fe3O4, and Au-Fe3O4Nanoheterodimers and Their Efficacy as Radiosensitizers in Cancer Therapy - Klein, Stefanie; Otto, Julia; Harreiß, Christina; Distel, Luitpold; Leistner, Angelika; Neuhuber, Winfried; Spiecker, Erdmann; Kryschi, Carola (ACS Applied Bio Materials, 2021)
The X-radiation enhancing effect of caffeic acid-functionalized Au-Fe3O4, Pt-Fe3O4, and Pd-Fe3O4 nanoheterodimers (NHDs) on 2D and 3D breast tumor (MCF-7) and healthy breast epithelial (MCF-10A) cells was comprehensively examined by performing cell viability, reactive oxygen species (ROS) detection, enzyme activity, and clonogenic assays. Intracellular NHDs were observed to cause DNA fragmentation and to enhance superoxide and hydroxyl radical formation in MCF-7 cells when exposed to a single dose of 1 Gy. MCF-7-derived multicellular tumor spheroids (MCF-7 MCTS) and MCF-10A-derived multicellular spheroids (MCF-10A MCS) were incubated with the NHDs and irradiated with five daily doses of 2 Gy. The Au-Fe3O4 and Pt-Fe3O4 NHD-loaded MCF-7 MCTS significantly decreased in volume after being exposed to fractionated irradiation, whereas intracellular Au-Fe3O4 and Pt-Fe3O4 NHDs promoted the growth of the irradiated MCF-10A MCS. Moreover, Au-Fe3O4 and Pt-Fe3O4 NHDs were shown to impede ROS formation and inhibit DNA strand breakage in the noncancerous MCF-10A cells. On the other hand, the Pd-Fe3O4 NHDs boosted X-radiation-induced damage of MCF-10 A cells, which was ascribed to impairment of the ROS scavenging enzyme activities. In summary, caffeic acid-functionalized Au-Fe3O4 and Pt-Fe3O4 NHDs performed as excellent X-radiation enhancing agents in breast tumor cells, while they protect healthy breast epithelial cells against X-radiation.
CRIS-Team Scopus Importer:2021-11-05
Keywords: Au-Fe; caffeic acid; MCF-10A; MCF-7; multicellular tumor spheroids; Pd-Fe; Pt-Fe; radiotherapy

QAMaster: A new software framework for phantom-based computed tomography quality assurance - Karius, Andre; Bert, Christoph (Journal of Applied Clinical Medical Physics, 2022)
The regular evaluation of imaging performance of computed tomography (CT) scanners is essential for CT quality assurance. For automation of this process, the software QAMaster was developed at the Universitätsklinikum Erlangen, which provides based on CT scans of the CatPhan® 504 (The Phantom Laboratory, Salem, USA) automated image quality analysis and documentation by evaluating CT number accuracy, spatial linearity, uniformity, contrast-noise-ratio, spatial resolution, noise, and slice thickness. Dose assessment is supported by calculations of the weighted computed tomography dose index (CTDIw) and weighted cone beam dose index (CBDIw). QAMaster was tested with CatPhan® 504 scans and compared to manual evaluations of these scans, whereby high consistency of the respective results was observed. The CT numbers, spatial linearity, uniformity, contrast-noise-ratio, noise, and slice thickness deviated by only (0.13 ± 0.25) HU, (0.02 ± 0.05) mm, (−0.01 ± 0.03)%, 0.8 ± 1.8, (0.131 ± 0.05) HU, and (0.004 ± 0.005) mm between both evaluations, respectively. The QAMaster results for spatial resolution did not differ significantly (p = 0.34) from the CatPhan® 504 based manual resolution assessment. Dose computations were fully consistent between QAMaster and manual calculations. Thus, QAMaster proved to be a comprehensive and functional software for performing an automated CT quality assurance routine. QAMaster will be open-source after its release.
CRIS-Team Scopus Importer:2022-03-25
Keywords: computed tomography; cone beam computed tomography; image quality assurance; phantom-based software framework

QOL After APBI (Multicatheter Brachytherapy) Versus WBI: 5-Year Results, Phase 3 GEC-ESTRO Trial - Schaefer, R.; Strnad, Vratislav; Polgar, C.; Uter, Wolfgang; Hildebrandt, G.; Ott, O. J.; Kauer-Dorner, D.; Knauerhase, H.; Major, T.; Lyczek, J.; Guinot, J. L.; Dunst, J.; et al. (2018)
EVALuna2:36515

QoL after multimodal treatment of rectal cancer with/without oxaliplatin (phase 3, CAO/ARO/AIO-04) - Kosmala, R.; Fokas, E.; Flentje, M.; Sauer, Rolf; Liersch, T.; Graeven, U.; Fietkau, Rainer; Hohenberger, Werner; Arnold, D.; Hofheinz, R.; Ghadimi, M.; Raab, H.; et al. (RADIOTHERAPY AND ONCOLOGY, 2019)
CRIS-Team WoS Importer:2019-06-18

Quality assurance and long-term stability of a novel 3-in-1 X-ray system for brachytherapy - Karius, Andre; Szkitsak, Juliane; Boronikolas, Vasilios; Fietkau, Rainer; Bert, Christoph (Journal of Applied Clinical Medical Physics, 2022)
Purpose A novel, mobile 3-in-1 X-ray system featuring radiography, fluoroscopy, and cone-beam computed tomography (CBCT) has been launched for brachytherapy recently. Currently, there is no quality assurance (QA) procedure explicitly applicable to this system equipped with innovative technologies such as dynamic jaws and motorized lasers. We developed a dedicated QA procedure and, based on its performance for a duration of 6 months, provide an assessment of the device's stability over time. Methods With the developed QA procedure, we assessed the system's planar and CBCT-imaging performance by investigating geometric accuracy, CT-number stability, contrast-noise-ratio, uniformity, spatial resolution, low-contrast detectability, dynamic range, and X-ray exposure using dedicated phantoms. Furthermore, we evaluated geometric stability by using the flexmap-approach and investigated the device's laser- and jaw-positioning accuracy with an in-house test phantom. CBCT- and planar-imaging protocols for pelvis, breast, and abdomen imaging were examined. Results Planar- and CBCT-imaging performances were widely stable with a geometric accuracy <= 1 mm, CT-number stability of up to 46 HU, and uniformity variations of up to 48 HU over time. For planar imaging, low-contrast detectability and dynamic range exceeded current recommendations. Although geometric stability was considered tolerable, partly substantial positioning inaccuracies of up to more than 120 mm and -13 mm were obtained for lasers and jaws, respectively. X-ray exposure showed small variations of <= 0.56 mu Gy and <= 0.76 mGy for planar- and CBCT-imaging, respectively. The conductance of the QA procedure allowed a smooth evaluation of the system's overall performance. Conclusion We developed a QA workflow for a novel 3-in-1 X-ray system allowing to assess the device's imaging and hardware performance. The system showed in general a reasonable imaging performance and stability over time, whereas improvements regarding laser and jaw accuracy are strictly required.
CRIS-Team WoS Importer:2022-07-29

Quality Assurance by electromagnetic Tracking in Interstitial multi-catheter HDR Brachytherapy Using a hybrid Afterloading System - Kallis, Karoline; Strnad, Vratislav; Fietkau, Rainer; Bert, Christoph (2018)
EVALuna2:36475

Quality assurance for dynamic tumor tracking - Witulla, Barbara; Ziegler, Marc; Brandt, Tobias; Prasetio, Heru; Fietkau, Rainer; Bert, Christoph (Zeitschrift für Medizinische Physik, 2021)
The purpose of this work was to develop a treatment plan verification routine for a linear accelerator dedicated to SBRT treatments with gimbal based dynamic tumor tracking using three commercially available phantoms. The accelerator system has two special features: It operates with a rotation of the ring shaped gantry instead of a couch rotation and target motion can be compensated for via a gimbal system (dynamic tumor tracking, DTT). DTT plans were each measured with the three different phantoms. Afterwards the measured dose distribution was compared with the calculated dose distribution via global Gamma Index analysis (3 mm / 3%, threshold: 10%). The global gamma pass rates were on average (93.5 ± 7.2) % for ArcCHECK, (98.0 ± 2.6) % for OCTAVIUS® 4D and (98.4 ± 4.2) % for MatriXX Evolution. All three systems could be used for quality assurance with ring rotations and DTT, however, each with limitations.
CRIS-Team Scopus Importer:2021-03-05
Keywords: Intensity modulated radiation therapy; quality assurance; Stereotactic body radiation therapy; Tumor Tracking

Quality assurance for interstitial brachytherapy using an EMT system integrated into an afterloader - Kallis, Karoline; Strnad, Vratislav; Fietkau, Rainer; Bert, Christoph (2018)
EVALuna2:36479

Quality assurance guidelines for superficial hyperthermia clinical trials: I. Clinical requirements - Trefna, Hana Dobsicek; Crezee, Hans; Schmidt, Manfred; Marder, Dietmar; Lamprecht, Ulf; Ehmann, Michael; Hartmann, Josefin; Nadobny, Jacek; Gellermann, Johanna; Van Holthe, Netteke; Ghadjar, Pirus; Lomax, Nicoletta; et al. (International Journal of Hyperthermia, 2017)
Quality assurance guidelines are essential to provide uniform execution of clinical trials and treatment in the application of hyperthermia. This document provides definitions for a good hyperthermia treatment and identifies the clinical conditions where a certain hyperthermia system can or cannot adequately heat the tumour volume. It also provides brief description of the characteristics and performance of the current electromagnetic (radiative and capacitive), ultrasound and infra-red heating techniques. This information helps to select the appropriate heating technique for the specific tumour location and size, and appropriate settings of the water bolus and thermometry. Finally, requirements of staff training and documentation are provided. The guidelines in this document focus on the clinical application and are complemented with a second, more technical quality assurance document providing instructions and procedure to determine essential parameters that describe heating properties of the applicator for superficial hyperthermia. Both sets of guidelines were developed by the ESHO Technical Committee with participation of senior STM members and members of the Atzelsberg Circle.
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Quality assurance guidelines for superficial hyperthermia clinical trials : II. Technical requirements for heating devices - Trefna, Hana Dobsicek; Crezee, Johannes; Schmidt, Manfred; Marder, Dietmar; Lamprecht, Ulf; Ehmann, Michael; Nadobny, Jacek; Hartmann, Josefin; Lomax, Nicolleta; Abdel-Rahman, Sultan; Curto, Sergio; Bakker, Akke; et al. (Strahlentherapie und Onkologie, 2017)
Quality assurance (QA) guidelines are essential to provide uniform execution of clinical trials with uniform quality hyperthermia treatments. This document outlines the requirements for appropriate QA of all current superficial heating equipment including electromagnetic (radiative and capacitive), ultrasound, and infrared heating techniques. Detailed instructions are provided how to characterize and document the performance of these hyperthermia applicators in order to apply reproducible hyperthermia treatments of uniform high quality. Earlier documents used specific absorption rate (SAR) to define and characterize applicator performance. In these QA guidelines, temperature rise is the leading parameter for characterization of applicator performance. The intention of this approach is that characterization can be achieved with affordable equipment and easy-to-implement procedures. These characteristics are essential to establish for each individual applicator the specific maximum size and depth of tumors that can be heated adequately. The guidelines in this document are supplemented with a second set of guidelines focusing on the clinical application. Both sets of guidelines were developed by the European Society for Hyperthermic Oncology (ESHO) Technical Committee with participation of senior Society of Thermal Medicine (STM) members and members of the Atzelsberg Circle.
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Quality Assurance in interstitial multi-catheter Brachytherapy using an electromagnetic Tracking System - Abu-Hossin, Nadin; Kallis, Karoline; Strnad, Vratislav; Fietkau, Rainer; Bert, Christoph (STRAHLENTHERAPIE UND ONKOLOGIE, 2019)
CRIS-Team WoS Importer:2019-06-07

Quality assurance of a breathing controlled four-dimensional computed tomography algorithm - Szkitsak, Juliane; Karius, Andre; Hofmann, Christian; Fietkau, Rainer; Bert, Christoph; Speer, Stefan (Physics and Imaging in Radiation Oncology, 2022)
Background & purpose: Four-dimensional computed tomography (4DCT) scans are standardly used for radiotherapy planning of tumors subject to respiratory motion. Based on online analysis and automatic adaption of scan parameters to the patient's individual breathing pattern, a new breathing-controlled 4DCT (i4DCT) algorithm attempts to counteract irregular breathing and thus prevent artifacts. The aim of this study was to perform an initial quality assurance for i4DCT. Material & methods: To validate the i4DCT algorithm, phantom measurements were performed to evaluate geometric accuracy (diameter, volume, eccentricity), image quality (dose-normalized contrast-noise-ratio, CT number accuracy), and correct representation of motion amplitude of simulated tumor lesions. Furthermore, the impact of patient weight and resulting table flexion on the measurements was investigated. Static three-dimensional CT (3DCT) scans were used as ground truth. Results: The median volume deviation magnitude between 4DCT and 3DCT was < 2% (<0.2 cm3). The volume differences ranged from –8% (–1.0 cm3) to 3% (0.4 cm3). Median tumor diameter deviation magnitudes were < 2% (<0.7 mm) for regular and < 3.5% (<1.0 mm) for irregular breathing. For eccentricity, a median deviation magnitude of < 0.05 for regular and < 0.08 for irregular breathing curves was found. The respiratory amplitude was represented with a median accuracy of < 0.5 mm. CT numbers and dose-normalized contrast-noise-ratio showed no clinically relevant difference between 4DCT and 3DCT. Table flexion proved to have no clinically relevant impact on geometric accuracy. Conclusions: The breathing-controlled algorithm provides in general good results regarding image quality, geometric accuracy, and correct depiction of motion amplitude for regular and irregular breathing.
CRIS-Team Scopus Importer:2022-07-22
Keywords: 4DCT; Quality assurance; Respiratory motion

Quality assurance of curved catheter paths in interstitial brachytherapy using a constructed phantom - Abu-Hossin, N.; Gulde, S.; Dürrbeck, Christopher; Strnad, Vratislav; Fietkau, Rainer; Bert, Christoph (RADIOTHERAPY AND ONCOLOGY, 2021)
CRIS-Team WoS Importer:2021-06-18

Quality of life in rectal cancer patients with or without oxaliplatin in the randomised CAO/ARO/AIO-04 phase 3 trial - Kosmala, Rebekka; Fokas, Emmanouil; Flentje, Michael; Sauer, Rolf; Liersch, Torsten; Graeven, Ullrich; Fietkau, Rainer; Hohenberger, Werner; Arnold, Dirk; Hofheinz, Ralf Dieter; Ghadimi, Michael; Ströbel, Philipp; et al. (European Journal of Cancer, 2021)
Background: The CAO/ARO/AIO trial has shown that oxaliplatin added to preoperative chemoradiotherapy and postoperative chemotherapy significantly improved disease-free survival in locally advanced rectal cancer (LARC). Here, we present a post-hoc analysis of quality of life (QoL) in disease-free patients. Patients and methods: Between 2006 and 2010, 1236 patients with LARC were randomly assigned either to preoperative chemoradiotherapy followed by total mesorectal excision and postoperative chemotherapy (N = 623) or combined with oxaliplatin (N = 613). QoL questionnaires (EORTC QLQ-C30, colorectal module CR38) were completed at baseline, after postoperative chemotherapy and during follow-up. Analysis was performed according intent-to-treat. Results: Available questionnaires (baseline) were 82% (N = 512) in the control and 84% (N = 513) in the investigational group. Response rates were 49% (533 of 1086) at 1 year and 43% (403 of 928) at 3 years. Global health status (GHS) for disease-free patients was stable in both groups (range 0–100). At baseline: standard arm 62.0 (mean, SD 21.6; N = 491) versus oxaliplatin arm 63.2 (mean, SD 22; N = 503); at 3 years: 69.4 (SD 19.3; N = 187) versus 65.4 (SD 22.2; N = 202). After treatment and at 3 years, no significant differences (≥10 points) between groups were found in QoL subscales. Disease-free patients experiencing neurotoxic side-effects (grade 1–4) showed reduced GHS at 3 years versus patients without neurotoxicity (mean 59.2 versus 69.3; P < 0.001), while grade 3–4 rate was low. Conclusion: The addition of oxaliplatin was not associated with worse overall QoL. This information is of interest to patients in many ongoing rectal cancer trials. Trial registration information: NCT00349076.
CRIS-Team Scopus Importer:2021-01-08
Keywords: Chemoradiotherapy; Oxaliplatin; Quality of life; Rectal neoplasms

Quality of Life of Patients with Head and Neck Cancer Receiving Cetuximab, Fluorouracil, Cisplatin Comparing to Cetuximab, Fluorouracil, Cisplatin, and Docetaxel within the CEFCID Trial - Goerling, Ute; Gauler, Thomas; Dietz, Andreas; Grünwald, Viktor; Knipping, Stephan; Guntinas-Lichius, Orlando; Frickhofen, Norbert; Lindeman, Hans Walter; Fietkau, Rainer; Haxel, Boris; Große-Thie, Christina; Maschmeyer, Georg; et al. (Oncology Research and Treatment, 2022)
Introduction: CeFCiD was a multicenter phase II study comparing the efficacy of cetuximab (C), 5-flourouracil, and cisplatin with the same regimen adding docetaxel (D) in recurrent/metastatic head and neck cancer. The primary analysis trial did not demonstrate survival benefit from therapy intensification in first-line recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN). The current analysis of the trial assessed the impact of treatment on quality of life (QoL). Methods: The European Organization for Research and Treatment of Cancer Quality of life Questionnaire QLQ-C30 and the tumor-specific module for head and neck cancer (QLQ-H&N35) were used to assess QoL at baseline (visit 1), after 2 (visit 3), 4 (visit 5), and 6 (visit 7) cycles of chemotherapy. Results: Of 180 patients included in this study, 86 patients (47.8%) completed the questionnaires at baseline. Considering selected scores over treatment time, there was no difference in global QoL, dyspnea, swallowing, and speech between the treatment arms in the course. For fatigue, a significant increase from baseline to visit 3 (p = 0.02), visit 5 (p = 0.002), and to visit 7 (p = 0.003) was observed for patients receiving D, cisplatin or carboplatin (P), 5-fluorouracil (F), and C. At the end of chemotherapy, the manifestation of fatigue was similar compared in the 2 treatment arms. Discussion/Conclusion: Therapy intensification not adversely affects selected scores of QoL of patients with recurrent and/or metastatic SCCHN. Nevertheless, fatigue seems to be pronounced in patients treated with D.
CRIS-Team Scopus Importer:2022-07-01
Keywords: Docetaxel; Head and neck cancer; Quality of life; Recurrent and metastatic; Therapy intensification

Quality of life of patients with newly diagnosed glioblastoma during TTFields therapy in routine clinical care: first results of the TIGER study - Baehr, O.; Tabatabai, G.; Fietkau, Rainer; Goldbrunner, R.; Glas, M. (STRAHLENTHERAPIE UND ONKOLOGIE, 2021)
CRIS-Team WoS Importer:2021-07-16

Quality-of-life results for accelerated partial breast irradiation with interstitial brachytherapy versus whole-breast irradiation in early breast cancer after breast-conserving surgery (GEC-ESTRO): 5-year results of a randomised, phase 3 trial - Schaefer, Rebekka; Strnad, Vratislav; Polgar, Csaba; Uter, Wolfgang; Hildebrandt, Guido; Ott, Oliver J.; Kauer-Dorner, Daniela; Knauerhase, Hellen; Major, Tibor; Lyczek, Jaroslaw; Guinot, Jose Luis; Dunst, Juergen; et al. (Lancet Oncology, 2018)
BACKGROUND: Previous results from the GEC-ESTRO trial showed that accelerated partial breast irradiation (APBI) using multicatheter brachytherapy in the treatment of early breast cancer after breast-conserving surgery was non-inferior to whole-breast irradiation in terms of local control and overall survival. Here, we present 5-year results of patient-reported quality of life. METHODS: We did this randomised controlled phase 3 trial at 16 hospitals and medical centres in seven European countries. Patients aged 40 years or older with 0-IIA breast cancer were randomly assigned (1:1) after breast-conserving surgery (resection margins ≥2 mm) to receive either whole-breast irradiation of 50 Gy with a boost of 10 Gy or APBI using multicatheter brachytherapy. Randomisation was stratified by study centre, tumour type, and menopausal status, with a block size of ten and an automated dynamic algorithm. There was no masking of patients or investigators. The primary endpoint of the trial was ipsilateral local recurrence. Here, we present 5-year results of quality of life (a prespecified secondary endpoint). Quality-of-life questionnaires (European Organisation for Research and Treatment of Cancer QLQ-C30, breast cancer module QLQ-BR23) were completed before radiotherapy (baseline 1), immediately after radiotherapy (baseline 2), and during follow-up. We analysed the data according to treatment received (as-treated population). Recruitment was completed in 2009, and long-term follow-up is continuing. The trial is registered at ClinicalTrials.gov, number NCT00402519. FINDINGS: Between April 20, 2004, and July 30, 2009, 633 patients had accelerated partial breast irradiation and 551 patients had whole-breast irradiation. Quality-of-life questionnaires at baseline 1 were available for 334 (53%) of 663 patients in the APBI group and 314 (57%) of 551 patients in the whole-breast irradiation group; the response rate was similar during follow-up. Global health status (range 0-100) was stable in both groups: at baseline 1, APBI group mean score 65·5 (SD 20·6) versus whole-breast irradiation group 64·6 (19·6), p=0·37; at 5 years, APBI group 66·2 (22·2) versus whole-breast irradiation group 66·0 (21·8), p=0·94. The only moderate, significant difference (difference of 10-20 points) between the groups was found in the breast symptoms scale. Breast symptom scores were significantly higher (ie, worse) after whole-breast irradiation than after APBI at baseline 2 (difference of means 13·6, 95% CI 9·7-17·5; p<0·0001) and at 3-month follow-up (difference of means 12·7, 95% CI 9·8-15·6; p<0·0001). INTERPRETATION: APBI with multicatheter brachytherapy was not associated with worse quality of life compared with whole-breast irradiation. This finding supports APBI as an alternative treatment option after breast-conserving surgery for patients with early breast cancer. FUNDING: German Cancer Aid.
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Quality requirements for MRI simulation in cranial stereotactic radiotherapy: a guideline from the German Taskforce “Imaging in Stereotactic Radiotherapy” - Putz, Florian; Bock, Michael; Schmitt, Daniela; Bert, Christoph; Blanck, Oliver; Ruge, Maximilian I.; Hattingen, Elke; Karger, Christian P.; Fietkau, Rainer; Grigo, Johanna; Schmidt, Manuel; Bäuerle, Tobias; et al. (Strahlentherapie und Onkologie, 2024)
Accurate Magnetic Resonance Imaging (MRI) simulation is fundamental for high-precision stereotactic radiosurgery and fractionated stereotactic radiotherapy, collectively referred to as stereotactic radiotherapy (SRT), to deliver doses of high biological effectiveness to well-defined cranial targets. Multiple MRI hardware related factors as well as scanner configuration and sequence protocol parameters can affect the imaging accuracy and need to be optimized for the special purpose of radiotherapy treatment planning. MRI simulation for SRT is possible for different organizational environments including patient referral for imaging as well as dedicated MRI simulation in the radiotherapy department but require radiotherapy-optimized MRI protocols and defined quality standards to ensure geometrically accurate images that form an impeccable foundation for treatment planning. For this guideline, an interdisciplinary panel including experts from the working group for radiosurgery and stereotactic radiotherapy of the German Society for Radiation Oncology (DEGRO), the working group for physics and technology in stereotactic radiotherapy of the German Society for Medical Physics (DGMP), the German Society of Neurosurgery (DGNC), the German Society of Neuroradiology (DGNR) and the German Chapter of the International Society for Magnetic Resonance in Medicine (DS-ISMRM) have defined minimum MRI quality requirements as well as advanced MRI simulation options for cranial SRT.
CRIS-Team Scopus Importer:2024-01-12
Keywords: Brain metastases; DEGRO; DGMP; DGNC; DGNR; DS-ISMRM; Guideline; Meningioma; MRI simulation; Pituitary adenoma; Stereotactic radiosurgery; Stereotactic radiotherapy; Trigeminal neuralgia; Vestibular schwannoma

Quantification of an external motion surrogate for quality assurance in lung cancer radiation therapy - Wölfelschneider, Jens; Brandt, Tobias; Lettmaier, Sebastian; Fietkau, Rainer; Bert, Christoph (BioMed Research International, 2014)
The purpose of this work was to validate the stability of the end exhale position in deep expiration breath hold (DEBH) technique for quality assurance in stereotactic lung tumor radiation therapy. Furthermore, a motion analysis was performed for 20 patients to evaluate breathing periods and baseline drifts based on an external surrogate. This trajectory was detected using stereo infrared (IR) cameras and reflective body markers. The respiratory waveform showed large interpatient differences in the end exhale position during irradiation up to 18.8 mm compared to the global minimum. This position depends significantly on the tumor volume. Also the baseline drifts, which occur mostly in posterior direction, are affected by the tumor size. Breathing periods, which depend mostly on the patient age, were in a range between 2.4 s and 7.0 s. Fifteen out of 20 patients, who showed a reproducible end exhale position with a deviation of less than 5 mm, might benefit from DEBH due to smaller planning target volumes (PTV) compared to free breathing irradiation and hence sparing of healthy tissue. Patients with larger uncertainties should be treated with more complex motion compensation techniques.
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Quantification of pretherapeutic Changes in Brain Metastases before stereotactic Radiotherapy - Putz, Florian; Görnert, Caroline; Voigt, R.; Grigo, Johanna; Masitho, Siti; Reissig, L.; Huang, Yixing; Weissmann, Thomas; Mansoorian, Sina; Schmidt, M.; Semrau, Sabine; Bert, Christoph; et al. (STRAHLENTHERAPIE UND ONKOLOGIE, 2022)
CRIS-Team WoS Importer:2022-06-03

Quantitative EEG may predict weaning failure in ventilated patients on the neurological intensive care unit - Welte, Tamara; Gabriel, Maria; Hopfengaertner, Ruediger; Rampp, Stefan; Gollwitzer, Stephanie; Lang, Johannes; Stritzelberger, Jenny; Reindl, Caroline; Madzar, Dominik; Sprügel, Maximilian; Huttner, Hagen; Kuramatsu, Joji; et al. (Scientific Reports, 2022)
Neurocritical patients suffer from a substantial risk of extubation failure. The aim of this prospective study was to analyze if quantitative EEG (qEEG) monitoring is able to predict successful extubation in these patients. We analyzed EEG-monitoring for at least six hours before extubation in patients receiving mechanical ventilation (MV) on our neurological intensive care unit (NICU) between November 2017 and May 2019. Patients were divided in 2 groups: patients with successful extubation (SE) versus patients with complications after MV withdrawal (failed extubation; FE), including reintubation, need for non-invasive ventilation (NIV) or death. Bipolar six channel EEG was applied. Unselected raw EEG signal underwent automated artefact rejection and Short Time Fast Fourier Transformation. The following relative proportions of global EEG spectrum were analyzed: relative beta (RB), alpha (RA), theta (RT), delta (RD) as well as the alpha delta ratio (ADR). Coefficient of variation (CV) was calculated as a measure of fluctuations in the different power bands. Mann–Whitney U test and logistic regression were applied to analyze group differences. 52 patients were included (26 male, mean age 65 ± 17 years, diagnosis: 40% seizures/status epilepticus, 37% ischemia, 13% intracranial hemorrhage, 10% others). Successful extubation was possible in 40 patients (77%), reintubation was necessary in 6 patients (12%), 5 patients (10%) required NIV, one patient died. In contrast to FE patients, SE patients showed more stable EEG power values (lower CV) considering all EEG channels (RB: p < 0.0005; RA: p = 0.045; RT: p = 0.045) with RB as an independent predictor of weaning success in logistic regression (p = 0.004). The proportion of the EEG frequency bands (RB, RA RT, RD) of the entire EEG power spectrum was not significantly different between SE and FE patients. Higher fluctuations in qEEG frequency bands, reflecting greater fluctuation in alertness, during the hours before cessation of MV were associated with a higher rate of complications after extubation in this cohort. The stability of qEEG power values may represent a non-invasive, examiner-independent parameter to facilitate weaning assessment in neurocritical patients.
CRIS-Team Scopus Importer:2022-05-20

Quantitative, multi-institutional evaluation of MR thermometry accuracy for deep-pelvic MR-hyperthermia systems operating in multi-vendor MR-systems using a new anthropomorphic phantom - Curto, Sergio; Aklan, Bassim; Mulder, Tim; Mils, Oliver; Schmidt, Manfred; Lamprecht, Ulf; Peller, Michael; Wessalowski, Ruediger; Lindner, Lars H.; Fietkau, Rainer; Zips, Daniel; Bellizzi, Gennaro G.; et al. (Cancers, 2019)
Clinical outcome of hyperthermia depends on the achieved target temperature, therefore target conformal heating is essential. Currently, invasive temperature probe measurements are the gold standard for temperature monitoring, however, they only provide limited sparse data. In contrast, magnetic resonance thermometry (MRT) provides unique capabilities to non–invasively measure the 3D–temperature. This study investigates MRT accuracy for MR–hyperthermia hybrid systems located at five European institutions while heating a centric or eccentric target in anthropomorphic phantoms with pelvic and spine structures. Scatter plots, root mean square error (RMSE) and Bland–Altman analysis were used to quantify accuracy of MRT compared to high resistance thermistor probe measurements. For all institutions, a linear relation between MRT and thermistor probes measurements was found with R2 (mean ± standard deviation) of 0.97 ± 0.03 and 0.97 ± 0.02, respectively for centric and eccentric heating targets. The RMSE was found to be 0.52 ± 0.31 °C and 0.30 ± 0.20 °C, respectively. The Bland–Altman evaluation showed a mean difference of 0.46 ± 0.20 °C and 0.13 ± 0.08 °C, respectively. This first multi–institutional evaluation of MR-hyperthermia hybrid systems indicates comparable device performance and good agreement between MRT and thermistor probes measurements. This forms the basis to standardize treatments in multi–institution studies of MR–guided hyperthermia and to elucidate thermal dose–effect relations.
CRIS-Team Scopus Importer:2019-11-15
Keywords: Anthropomorphic phantom; Magnetic resonance imaging–guided hyperthermia; Magnetic resonance thermometry; Quality assurance; Radiofrequency hyperthermia; Thermistor probe

Questionnaire-based detection of immune-related adverse events in cancer patients treated with PD-1/PD-L1 immune checkpoint inhibitors - Griewing, Luisa Maria; Schweizer, Claudia; Schubert, Philipp; Rutzner, Sandra; Eckstein, Markus; Frey, Benjamin; Haderlein, Marlen; Weissmann, Thomas; Semrau, Sabine; Gostian, Antoniu Oreste; Mueller, Sarina K.; Traxdorf, Maximilian; et al. (BMC Cancer, 2021)
Background: Immune checkpoint inhibitors (ICI) have become standard treatment in different tumor entities. However, safe treatment with ICI targeting the PD-1/PD-L1 axis requires early detection of immune-related adverse events (irAE). There exist different questionnaires of drug manufacturers for the detection of irAE that have not been validated so far. Methods: The prospective non-interventional ST-ICI trial studied treatment with PD-1/PD-L1 ICI alone or combined with radiotherapy. In the current analysis, the detection rate of self-reported irAE with a patient questionnaire containing 41 different questions was compared to clinician-reported irAE. Results: Between April 2017 and August 2019, a total of 104 patients were prospectively enrolled. NSCLC (44%) and HNSCC (42%) were the most frequent tumor entities. A total of 784 questionnaires were collected. A total of 29 irAE were reported by clinicians. The most frequent irAE was hypothyroidism (9%), followed by skin reactions (5%), hepatitis (4%), diarrhea (3%), and pneumonitis (3%). Questions that became significantly more often positive at time points of clinician-reported irAE were “weight change”, “difficulty to grip things”, “bloody or mucous stool” and “insomnia”. Self-reported organ-specific questions detected at least 50% of clinician-reported irAE of gastrointestinal, lung, endocrine, and skin irAE. It was not possible to detect hepatic irAE with the questionnaire. Conclusion: Questionnaires can help to detect gastrointestinal, lung, endocrine, or skin irAE, but not hepatic irAE. Questions on “weight change” and “insomnia” may help to increase the detection rate of irAE, besides organ-specific questions. These results are a valuable contribution to the future development of a specific and practicable questionnaire for early self-reported detection of irAE during ICI therapy in cancer patients. Trial registration: ClinicalTrials.gov, NCT03453892. Registered on 05 March 2018.
CRIS-Team Scopus Importer:2021-04-09
Keywords: Immune checkpoint inhibitors; Immune-related adverse events; Patient-reported irAE; PD-1; PD-L1; Questionnaire; Side effects; Solid tumors; Toxicity

R0 resection following chemo (radio)therapy improves survival of primary inoperable pancreatic cancer patients. Interim results of the German randomized CONKO-007± trial - Fietkau, Rainer; Grützmann, Robert; Wittel, U. A.; Croner, R. S.; Jacobasch, L.; Neumann, U. P.; Reinacher-Schick, A.; Imhoff, D.; Boeck, S.; Keilholz, L.; Oettle, H.; Hohenberger, Werner; et al. (Strahlentherapie und Onkologie, 2020)
Purpose: Chemotherapy with or without radiotherapy is the standard in patients with initially nonmetastatic unresectable pancreatic cancer. Additional surgery is in discussion. The CONKO-007 multicenter randomized trial examines the value of radiotherapy. Our interim analysis showed a significant effect of surgery, which may be relevant to clinical practice. Methods: One hundred eighty patients received induction chemotherapy (gemcitabine or FOLFIRINOX). Patients without tumor progression were randomized to either chemotherapy alone or to concurrent chemoradiotherapy. At the end of therapy, a panel of five independent pancreatic surgeons judged the resectability of the tumor. Results: Following induction chemotherapy, 126/180 patients (70.0%) were randomized to further treatment. Following study treatment, 36/126 patients (28.5%) underwent surgery; (R0: 25/126 [19.8%]; R1/R2/Rx [n = 11/126; 6.1%]). Disease-free survival (DFS) and overall survival (OS) were significantly better for patients with R0 resected tumors (median DFS and OS: 16.6 months and 26.5 months, respectively) than for nonoperated patients (median DFS and OS: 11.9 months and 16.5 months, respectively; p = 0.003). In the 25 patients with R0 resected tumors before treatment, only 6/113 (5.3%) of the recommendations of the panel surgeons recommended R0 resectability, compared with 17/48 (35.4%) after treatment (p < 0.001). Conclusion: Tumor resectability of pancreatic cancer staged as unresectable at primary diagnosis should be reassessed after neoadjuvant treatment. The patient should undergo surgery if a resectability is reached, as this significantly improves their prognosis.
CRIS-Team Scopus Importer:2020-09-25
Keywords: Neoadjuvant chemoradiotherapy; Pancreatic adenocarcinoma; Prospective randomized multicenter trial; Surgery; Tumor resectability

Radiation and checkpoint Blockade in the treatment of metastases - Hirschmann, Eva; Gaipl, Udo; Fietkau, Rainer; Distel, Luitpold; Hecht, Markus (2018)
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Radiation Immunotherapy has different effects on the immunological Composition of the Tumor Microenvironment in primary and abscopic Murine Tumors - Rueckert, M.; Deloch, Lisa; Frey, Benjamin; Fietkau, Rainer; Gaipl, Udo (STRAHLENTHERAPIE UND ONKOLOGIE, 2020)
CRIS-Team WoS Importer:2020-10-02

Radiation Induced DNA Double-Strand Breaks in Radiology - Kuefner, M. A.; Brand, Michael; Engert, C.; Schwab, S. A.; Uder, Michael (Röfo-Fortschritte auf dem Gebiet der Röntgenstrahlen und der bildgebenden Verfahren, 2015)
Shortly after the discovery of X-rays, their damaging effect on biological tissues was observed. The determination of radiation exposure in diagnostic and interventional radiology is usually based on physical measurements or mathematical algorithms with standardized dose simulations. ?-H2AX immunofluorescence microscopy is a reliable and sensitive method for the quantification of radiation induced DNA double-strand breaks (DSB) in blood lymphocytes. The detectable amount of these DNA damages correlates well with the dose received. However, the biological radiation damage depends not only on dose but also on other individual factors like radiation sensitivity and DNA repair capacity. Iodinated contrast agents can enhance the x-ray induced DNA damage level. After their induction DSB are quickly repaired. A protective effect of antioxidants has been postulated in experimental studies. This review explains the prinicple of the ?-H2AX technique and provides an overview on studies evaluating DSB in radiologic examinations.Radiologic examinations including CT and angiography induce DNA double-strand breaks. Even after mammography a slight but significant increase is detectable in peripheral blood lymphocytes. The number of radiation induced double-strand breaks correlates well with the radiation dose. Individual factors including radiation sensitivity, DNA repair capacity and the application of iodinated contrast media has an influence on the DNA damage level.
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Radiation Sensitivity in Patients with Prostate Cancer - Altmann, J. -M.; Schuster, Barbara; Geinitz, H.; Fietkau, Rainer; Distel, Luitpold (STRAHLENTHERAPIE UND ONKOLOGIE, 2021)
CRIS-Team WoS Importer:2021-07-16

Radiation therapy in Graves'-opthalmopathy - Weissmann, T.; Semrau, S.; Ott, O. J.; Fietkau, Rainer; Putz, Florian (STRAHLENTHERAPIE UND ONKOLOGIE, 2019)
CRIS-Team WoS Importer:2019-06-07

Radiochemotherapy and interstitial brachytherapy for cervical cancer: clinical results and patient-reported outcome measures - Alfrink, Johanna; Aigner, Thomas; Zoche, Hermann; Distel, Luitpold; Grabenbauer, Gerhard (Strahlentherapie und Onkologie, 2024)
Objective: To evaluate clinical results and long-term patient-reported outcome measures (PROMs) on quality of life in cervical cancer patients following radiochemotherapy (RCT) and brachytherapy (BT) as definitive treatment. Materials and methods: Between 2003 and 2023, a total of 132 patients with advanced cervical cancer were evaluated for possible treatment. Patients treated by postoperative RCT, palliative radiotherapy, and those treated for recurrent disease were excluded. Thus, 46 patients receiving standard RCT and BT as their curative treatment were included in this study. PROMs were assessed prospectively by patients’ self-completion of the EORTC-QLQ-C30 and EORTC-QLQ-CX24 questionnaires. Results: Five-year overall survival (OS), distant metastases-free survival (DMFS), and pelvic tumor-free survival rates (PTFS) were 53%, 54%, and 83%, respectively. A significant impact on OS was seen for FIGO (International Federation of Gynecologic Oncology) stage (IIB–IIIA: 79% vs. IIIB–IVA: 33%, p = 0.015), for overall treatment time (OTT; 50–65 d: 64% vs. > 65 d: 38%, p = 0.004), and for rectal D2cc (≤ 73 Gy: 50% vs. > 73 Gy: 38%, p = 0.046). The identical parameters were significantly associated with DMFS (FIGO stage: p = 0.012, OTT: p = 0.008, D2cc: p = 0.024). No parameters with a significant influence on PTFS were seen. In multivariate analysis, an impact of FIGO stage on OS (p = 0.05) and DMFS (p = 0.014) was detected, and of rectal D2cc on DMFS (p = 0.031). The overall QoL score was 63/100. Cognitive function was the least impaired (84/100), while role functioning was the worst (67/100). On the symptom scale, insomnia (46/100), fatigue (41/100), dyspnea (32/100), pain (26/100), and financial difficulties (25/100) were scored the worst. According to EORTC-QLQ-CX24, peripheral neuropathy (36/100) and lymphedema (32/100) occurred most frequently. Impaired sexual/vaginal functioning (32/100) and body image (22/100) were also frequently recorded. Conclusion: In patients with advanced cervical cancer, a combination of RCT and BT remains an excellent treatment option. In terms of patient-reported long-term quality of life, specific support is needed to alleviate symptoms including lymphedema, peripheral neuropathy, and impaired sexual activity.
CRIS-Team Scopus Importer:2024-02-16
Keywords: External radiation and interstitial brachytherapy; Locally advanced cervical cancer; Quality of life; Questionnaires; Radiochemotherapy

Radio(chemo)therapy does differently impact on PD-L1 and PD-L2 expression in human melanoma cell lines - Derer, Anja; Riegel, D.; Frey, Benjamin; Fietkau, Rainer; Gaipl, Udo (2018)
EVALuna2:36496

Radio(chemo)therapy in anaplastic thyroid cancer—high locoregional but low distant control rates—a monocentric analysis of a tertiary referral center - Schmied, Matthias; Lettmaier, Sebastian; Semrau, Sabine; Traxdorf, Maximilian; Mantsopoulos, Konstantinos; Müller-Hübner, Sarina; Iro, Heinrich; Denz, Axel; Grützmann, Robert; Fietkau, Rainer; Haderlein, Marlen (Strahlentherapie und Onkologie, 2022)
Background: Anaplastic thyroid cancer (ATC) is a lethal disease with highly aggressive disease progression. This study analyses the influence of radio(chemo)therapy, R(C)T, on disease control, survival rates and predictors for survival. Patients and methods: A total of 33 patients with ATC, treated at a tertiary referral center between May 2001 and April 2020 were included. Univariate and multivariate analysis were used to investigate correlates of R(C)T and predictors on disease control and survival rates. Results: Median follow-up was 4 months. In UICC stage IVA and IVB median overall survival (OS) was 8 months, median progression-free survival (PFS) was 6 months. Patients with UICC stage IVA and IVB and patients being irradiated with a radiation dose of more than 60 Gy showed increased OS. Of these patients, 3 were alive and free from disease. All of them receiving cisplatin-based radiochemotherapy and a minimum radiation dose of 66 Gy. UICC stage IVC showed a median OS of 2.5 months and a median PFS of 1 month. Only 2 of 16 patients had local failure. Conclusion: Depending on UICC stage, RT with high radiation dose can lead to improved OS or at least higher locoregional control. A limiting factor is the high incidence of distant metastases; therefore modern systemic treatment options should be integrated into multimodal therapy concepts.
CRIS-Team Scopus Importer:2022-05-20
Keywords: Anaplastic thyroid cancer; Chemotherapy; Multimodal treatment; Radiation dose; Radiotherapy

Radiochemotherapy with or without cetuximab for unresectable esophageal cancer: final results of a randomized phase 2 trial (LEOPARD-2) - Rades, Dirk; Bartscht, Tobias; Hunold, Peter; Schmidberger, Heinz; König, Laila; Debus, Jürgen; Belka, Claus; Homann, Nils; Spillner, Patrick; Petersen, Cordula; Kuhnt, Thomas; Fietkau, Rainer; et al. (Strahlentherapie und Onkologie, 2020)
Purpose: To investigate the efficacy and toxicity of cetuximab when added to radiochemotherapy for unresectable esophageal cancer. Methods: This randomized phase 2 trial (clinicaltrials.gov, identifier NCT01787006) compared radiochemotherapy plus cetuximab (arm A) to radiochemotherapy (arm B) for unresectable esophageal cancer. Primary objective was 2‑year overall survival (OS). Arm A was considered insufficiently active if 2‑year OS was ≤40% (null hypothesis = H0), and promising if the lower limit of the 95% confidence interval was >45%. If that lower limit was >40%, H0 was rejected. Secondary objectives included progression-free survival (PFS), locoregional control (LC), metastases-free survival (MFS), response, and toxicity. The study was terminated early after 74 patients; 68 patients were evaluable. Results: Two-year OS was 71% in arm A (95% CI: 55–87%) vs. 53% in arm B (95% CI: 36–71%); H0 was rejected. Median OS was 49.1 vs. 24.1 months (p = 0.147). Hazard ratio (HR) for death was 0.60 (95% CI: 0.30–1.21). At 2 years, PFS was 56% vs. 44%, LC 84% vs. 72%, and MFS 74% vs. 54%. HRs were 0.51 (0.25–1.04) for progression, 0.43 (0.13–1.40) for locoregional failure, and 0.43 (0.17–1.05) for distant metastasis. Overall response was 81% vs. 69% (p = 0.262). Twenty-six and 27 patients, respectively, experienced at least one toxicity grade ≥3 (p = 0.573). A significant difference was found for grade ≥3 allergic reactions (12.5% vs. 0%, p = 0.044). Conclusion: Given the limitations of this trial, radiochemotherapy plus cetuximab was feasible. There was a trend towards improved PFS and MFS. Larger studies are required to better define the role of cetuximab for unresectable esophageal cancer.
CRIS-Team Scopus Importer:2020-06-19
Keywords: Definitive treatment; Efficacy; EGFR antibody; Esophageal cancer; Feasibility

Radio-Immunotherapy-Induced Immunogenic Cancer Cells as Basis for Induction of Systemic Anti-Tumor Immune Responses - Pre-Clinical Evidence and Ongoing Clinical Applications - Derer, Anja; Deloch, Lisa; Rubner, Yvonne; Fietkau, Rainer; Frey, Benjamin; Gaipl, Udo (Frontiers in Immunology, 2015)
Radiotherapy (RT) primarily aims to locally destroy the tumor via the induction of DNA damage in the tumor cells. However, the so-called abscopal, namely systemic and immune-mediated, effects of RT move over more and more in the focus of scientists and clinicians since combinations of local irradiation with immune therapy have been demonstrated to induce anti-tumor immunity. We here summarize changes of the phenotype and microenvironment of tumor cells after exposure to irradiation, chemotherapeutic agents, and immune modulating agents rendering the tumor more immunogenic. The impact of therapy-modified tumor cells and damage-associated molecular patterns on local and systemic control of the primary tumor, recurrent tumors, and metastases will be outlined. Finally, clinical studies affirming the bench-side findings of interactions and synergies of radiation therapy and immunotherapy will be discussed. Focus is set on combination of radio(chemo)therapy (RCT) with immune checkpoint inhibitors, growth factor inhibitors, and chimeric antigen receptor T-cell therapy. Well-deliberated combination of RCT with selected immune therapies and growth factor inhibitors bear the great potential to further improve anti-cancer therapie
EVALuna2:18276

Radio-immunotherapy: the focused beam expands - Frey, Benjamin; Gaipl, Udo (Lancet Oncology, 2015)
EVALuna2:18299

Radioimmuntherapie - Hecht, Markus; Gaipl, Udo; Fietkau, Rainer (Onkologe, 2021)
Background: Radiotherapy is used to achieve local tumor control in the irradiated area. In the last decade, there has been increasing evidence that radiotherapy has immunomodulatory properties in addition to killing tumor cells. Purpose: Essential principles of the immunomodulatory effects of radiotherapy are explained and, in particular, the clinical benefits of radiotherapy in combination with immune checkpoint inhibitors are presented. Results: Radiotherapy can trigger tumor-specific immune responses by inducing immunogenic cell death of tumor cells and alterations of the tumor microenvironment. However, clinical relevance of such systemic immunologic effects of local irradiation has been observed only very rarely in the past, which is probably due to the fact that irradiation can also induce immunosuppressive effects. By combining local radiotherapy with immune checkpoint inhibitors, antitumor immune responses can be enhanced and immunosuppressive effects can be counteracted. Such therapeutic strategies are currently being investigated in numerous clinical trials and have achieved remarkable results in non-small cell lung cancer (stage III) with the PD-L1 inhibitor durvalumab after definitive radiochemotherapy. Conclusion: The combination of radiotherapy with immune checkpoint inhibitors is an efficient concept that is currently being investigated in numerous studies and has already entered clinical routine in non-small cell lung cancer.
CRIS-Team Scopus Importer:2021-09-10
Keywords: Immune checkpoint inhibitors; Immunogenic cell death; Immunotherapy; PD‑1; Radiotherapy

Radiomics for selection of patients treated with immuno-radiotherapy: pooled analysis from 6 studies - Sun, R.; Sundahl, N.; Hecht, Markus; Putz, Florian; Lancia, A.; Milic, M.; Carre, A.; Lerousseau, M.; Theo, E.; Battistella, E.; Andres, E. Alvarez; Louvel, G.; et al. (RADIOTHERAPY AND ONCOLOGY, 2020)
CRIS-Team WoS Importer:2021-06-18

Radiomics to predict outcomes and abscopal response of patients with cancer treated with immunotherapy combined with radiotherapy using a validated signature of CD8 cells - Sun, Roger; Sundahl, Nora; Hecht, Markus; Putz, Florian; Lancia, Andrea; Rouyar, Angela; Milic, Marina; Carré, Alexandre; Battistella, Enzo; Alvarez Andres, Emilie; Niyoteka, Stéphane; Romano, Edouard; et al. (Journal for ImmunoTherapy of Cancer, 2020)
BACKGROUND: Combining radiotherapy (RT) with immuno-oncology (IO) therapy (IORT) may enhance IO-induced antitumor response. Quantitative imaging biomarkers can be used to provide prognosis, predict tumor response in a non-invasive fashion and improve patient selection for IORT. A biologically inspired CD8 T-cells-associated radiomics signature has been developed on previous cohorts. We evaluated here whether this CD8 radiomic signature is associated with lesion response, whether it may help to assess disease spatial heterogeneity for predicting outcomes of patients treated with IORT. We also evaluated differences between irradiated and non-irradiated lesions. METHODS: Clinical data from patients with advanced solid tumors in six independent clinical studies of IORT were investigated. Immunotherapy consisted of 4 different drugs (antiprogrammed death-ligand 1 or anticytotoxic T-lymphocyte-associated protein 4 in monotherapy). Most patients received stereotactic RT to one lesion. Irradiated and non-irradiated lesions were delineated from baseline and the first evaluation CT scans. Radiomic features were extracted from contrast-enhanced CT images and the CD8 radiomics signature was applied. A responding lesion was defined by a decrease in lesion size of at least 30%. Dispersion metrices of the radiomics signature were estimated to evaluate the impact of tumor heterogeneity in patient's response. RESULTS: A total of 94 patients involving multiple lesions (100 irradiated and 189 non-irradiated lesions) were considered for a statistical interpretation. Lesions with high CD8 radiomics score at baseline were associated with significantly higher tumor response (area under the receiving operating characteristic curve (AUC)=0.63, p=0.0020). Entropy of the radiomics scores distribution on all lesions was shown to be associated with progression-free survival (HR=1.67, p=0.040), out-of-field abscopal response (AUC=0.70, p=0.014) and overall survival (HR=2.08, p=0.023), which remained significant in a multivariate analysis including clinical and biological variables. CONCLUSIONS: These results enhance the predictive value of the biologically inspired CD8 radiomics score and suggests that tumor heterogeneity should be systematically considered in patients treated with IORT. This CD8 radiomics signature may help select patients who are most likely to benefit from IORT.
CRIS-Team Scopus Importer:2020-11-27
Keywords: radioimmunotherapy; translational medical research; tumor biomarkers; tumor microenvironment

Radioresistance shapes the immunogenic Properties of Triple-negative Breast Cancer Cells - Gehre, S.; Rückert, Michael; Sengedorj, Azzaya; Grottker, F.; Reichardt, Clara; Meyer, F.; Borgmann, K.; Fietkau, Rainer; Gaipl, Udo (STRAHLENTHERAPIE UND ONKOLOGIE, 2022)
CRIS-Team WoS Importer:2022-06-03

Radiosensitization by BRAF inhibitor therapy-mechanism and frequency of toxicity in melanoma patients - Hecht, Markus; Zimmer, L.; Loquai, C.; Weishaupt, C.; Gutzmer, R.; Schuster, B.; Gleisner, S.; Schulze, B.; Goldinger, S. M.; Berking, C.; Forschner, A.; Clemens, P.; et al. (Annals of Oncology, 2015)
Recent evidence suggests that ionizing radiation may be associated with unexpected side-effects in melanoma patients treated with concomitant BRAF inhibitors. A large multicenter analysis was carried out to generate reliable safety data and elucidate the mechanism.A total of 161 melanoma patients from 11 European skin cancer centers were evaluated for acute and late toxicity, of whom 70 consecutive patients received 86 series of radiotherapy with concomitant BRAF inhibitor therapy. To further characterize and quantify a possible radiosensitization by BRAF inhibitors, blood samples of 35 melanoma patients were used for individual radiosensitivity testing by fluorescence in situ hybridization of chromosomal breaks after ex vivo irradiation.With radiotherapy and concomitant BRAF inhibitor therapy the rate of acute radiodermatitis >=2° was 36% and follicular cystic proliferation was seen in 13% of all radiotherapies. Non-skin toxicities included hearing disorders (4%) and dysphagia (2%). Following whole-brain radiotherapy, rates of radiodermatitis >=2° were 44% and 8% (P < 0.001) for patients with and without BRAF inhibitor therapy, respectively. Concomitant treatment with vemurafenib induced acute radiodermatitis >=2° more frequently than treatment with dabrafenib (40% versus 26%, P = 0.07). In line with these findings, analysis of chromosomal breaks ex vivo indicated significantly increased radiosensitivity for patients under vemurafenib (P = 0.004) and for patients switched from vemurafenib to dabrafenib (P = 0.002), but not for patients on dabrafenib only. No toxicities were reported after stereotactic treatment.Radiotherapy with concomitant BRAF inhibitor therapy is feasible with an acceptable increase in toxicity. Vemurafenib is a more potent radiosensitizer than dabrafenib.
EVALuna2:18285

Radiosensitizing and radioprotecting effect of kinase-inhibitor Palbociclib in different normal tissue and cancer cell lines - Jost, Tina; Hecht, Markus; Fietkau, Rainer; Distel, Luitpold (2018)
EVALuna2:36494

Radiotherapy after skin-sparing mastectomy with immediate breast reconstruction in intermediate-risk breast cancer - Hehr, Thomas; Baumann, René; Budach, Wilfried; Duma, Marciana Nona; Dunst, Jürgen; Feyer, Petra; Fietkau, Rainer; Haase, Wulf; Harms, Wolfgang; Krug, David; Piroth, Marc D.; Sedlmayer, Felix; et al. (Strahlentherapie und Onkologie, 2019)
Background: Skin-sparing (SSME) and nipple-sparing mastectomy (NSME) were developed to improve the cosmetic results for breast cancer (BC) patients, both allowing for immediate breast reconstruction. Recommendations for post-mastectomy radiotherapy (PMRT) are primarily derived from trials where patients were treated by standard mastectomies. Due to their more conservative character, SSME and especially NSME potentially leave more glandular tissue at risk for subclinical disease. Methods: Rates and sites of locoregional failures following SSME and NSME plus/minus reconstruction were analyzed regarding tumor stage and biological risk factors. In particular, the role of PMRT in “intermediate”-risk and early stage high-risk breast cancer patients was revisited. Implications on targeting and dose delivery of PMRT were critically reviewed. Results: The value of PMRT in stage III BC remains undisputed. For node-negative BC patients, the majority of reports classify clinical and biological features such as tumor size, close surgical margins, premenopausal status, multicentricity, lymphangiosis, triple-negativity, HER2-overexpression, and poor tumor grading as associated with higher rates of locoregional relapse, thus, building an “intermediate” risk group. Surveys revealed that the majority of radiation oncologists use risk-adaptive models also considering the number of coinciding factors for the estimation of recurrence probability following SSME and NSME. Constellations with a 10-year locoregional recurrence risk of >10% are usually triggering the indication for PMRT. There was no common belief that the amount of residual tissue, e.g., tissue thickness over flaps, serves as additional decision aid. Modern treatment planning can ensure optimal dose distribution for PMRT in almost all patients with SSME. There are no reliable data supporting a reduction of the treatment volume from the CTV chest wall, e.g., to the nipple-areola complex, to the dorsal aspect behind the implant volume, the pectoralis muscle, nor the regional interpectoral, axillary, or complete regional lymph nodes only. The omission of a skin bolus in intermediate-risk BC does not compromise oncological safety. Conclusions: For intermediate-risk as well as early stage high-risk BC patients, the DEGRO Breast Cancer Expert Panel recommends the use of PMRT following SSME and NSME when a 10-year locoregional recurrence risk is likely to be greater than 10%, as estimated by clinical and biological risk factors. Subvolume-only radiation is discouraged outside of trials. The impact of adequate systemic treatment and the value of radiotherapy on optimal locoregional tumor control, with the goal of less than 5% LRR at 10-years follow-up, has to be verified in prospective trials.
CRIS-Team Scopus Importer:2019-09-03
Keywords: Intermediate-risk breast cancer; Local recurrence; Nipple-sparing mastectomy; PMRT; Post-mastectomy radiotherapy; Skin-sparing mastectomy

Radiotherapy and the immune system: More than just immune suppression - Rückert, Michael; Flohr, Ann-Sophie; Hecht, Markus; Gaipl, Udo (Stem Cells, 2021)
Radiotherapy (RT) is still one of the standard cancer therapies with up to two third of all cancer patients with solid tumors being irradiated in the course of their disease. The aim of using ionizing radiation in fractionated treatment schedules was always to achieve local tumor control by inducing DNA damage which can be repaired by surrounding normal tissue but leads to cell death in tumor cells. Meanwhile, it is known that RT also has immunological effects reshaping the tumor microenvironment. Nevertheless, RT alone often fails to elicit potent antitumor immune responses as these effects can be immunostimulatory as well as immunosuppressive. Here, we discuss how immunotherapies can be exploited in combined therapies to boost RT-induced antitumor immune responses or to counteract preexisting and RT-mediated immunosuppression to improve local and systemic tumor control. Furthermore, we highlight some parameters of radioimmunotherapies (RITs) which are under investigation for potential optimizations and how RIT approaches are tested in first phases II and III trials. Finally, we discuss how RT might affect normal and cancer stem cells.
CRIS-Team WoS Importer:2021-05-28

Radiotherapy combined with docetaxel alters the immune phenotype of HNSCC cells and results in increased surface expression of CD137 and release of HMGB1 of specifically HPV-positive tumor cells - Grottker, Fridolin; Gehre, Simon; Reichardt, Clara; Sengedorj, Azzaya; Jost, Tina; Rieckmann, Thorsten; Hecht, Markus; Gostian, Antoniu-Oreste; Frey, Benjamin; Fietkau, Rainer; Gaipl, Udo; Rückert, Michael (Neoplasia, 2023)
Purpose: Human papilloma virus (HPV) positive head and neck squamous cell carcinoma (HNSCC) tumors respond significantly better to anticancer treatments. It is assumed to be due to a better response to radiotherapy (RT), and presumably to an increased immunogenicity. However, little is known how the immune phenotype of HNSCC tumor cells is modulated by standard treatment, namely by radiochemotherapy (RCT). Methods: Therefore, we aimed to examine the impact of the HPV status on the immune phenotype of HNSCC cell lines following RCT with 5 × 3Gy or 1 × 19.3Gy and/or docetaxel, by analyzing cell death, release of damage-associated molecular patterns (DAMPs), surface expression of immune checkpoint molecules (ICMs) and the impact on activation of human monocyte-derived dendritic cells (hmDCs). Results: Cell death induction and Hsp70 release following RCT was independent of the HPV status, and RCT significantly increased the expression of the immune suppressive ICMs PD-L1, PD-L2 and HVEM. An immune stimulatory ICM, CD137, was significantly increased following RCT only on HPV-positive cell lines, as well as the release of HMGB1. Although the treatment increased cell death and modulated ICM expression in HNSCC, the hmDCs were not activated after co-incubation with treated tumor cells. Conclusion: Our data with the HPV-dependent release of HMGB1 and increased expression of CD137 following RCT provide a hint for increased immunogenicity underlining the better prognosis for HPV positive tumors following RCT.
CRIS-Team Scopus Importer:2023-11-24
Keywords: Anti-tumor immunity; Dendritic cells; Docetaxel; Head and neck squamous cell carcinoma; HMGB1; HPV status; Immune checkpoint molecules; Radiotherapy

Radiotherapy for benign achillodynia. Long-term results of the Erlangen Dose Optimization Trial - Ott, Oliver J.; Jeremias, Carolin; Gaipl, Udo; Frey, Benjamin; Schmidt, Manfred; Fietkau, Rainer (Strahlentherapie und Onkologie, 2015)
The aim of this study was to evaluate the long-term efficacy of two dose-fractionation schedules for radiotherapy of achillodynia.Between February 2006 and February 2010, 112 evaluable patients were recruited for this prospective trial. All patients received orthovoltage radiotherapy. One course consisted of 6 fractions/3 weeks. In the case of insufficient remission of pain after 6 weeks, a second series was performed. Patients were randomly assigned to receive either single doses of 0.5 or 1.0 Gy. The endpoint was pain reduction. Pain was measured before, right after (early response), 6 weeks after (delayed response), and approximately 2 years after radiotherapy (long-term response) with a questionnaire-based visual analogue scale (VAS) and a comprehensive pain score (CPS).The median follow-up was 24 months (range, 11-56). The overall early, delayed, and long-term response rates for all patients were 84 %, 88 %, and 95 %, respectively. The mean VAS values before treatment for early, delayed, and long-term responses for the 0.5-Gy and 1.0-Gy groups were 55.7 ± 21.0 and 58.2 ± 23.5 (p = 0.53), 38.0 ± 23.2 and 30.4 ± 22.6 (p = 0.08), 35.5 ± 25.9 and 30.9 ± 25.4 (p = 0.52), and 11.2 ± 16.4 and 15.3 ± 18.9 (p = 0.16), respectively. The mean CPS values before treatment for early, delayed, and long-term responses were 8.2 ± 3.0 and 8.9 ± 3.3 (p = 0.24), 5.6 ± 3.1 and 5.4 ± 3.3 (p = 0.76), 4.4 ± 2.6 and 5.3 ± 3.8 (p = 0.58), and 2.2 ± 2.9 and 2.8 ± 3.3 (p = 0.51), respectively. No significant differences in long-term response quality between the two arms was found (p = 0.73).Radiotherapy is a very effective treatment for the management of benign achillodynia. For radiation protection, the dose for a radiotherapy series should not exceed 3.0 Gy.
EVALuna2:18279

Radiotherapy for benign calcaneodynia: long-term results of the Erlangen Dose Optimization (EDO) trial - Ott, Oliver J.; Jeremias, Carolin; Gaipl, Udo; Frey, Benjamin; Schmidt, Manfred; Fietkau, Rainer (Strahlentherapie und Onkologie, 2014)
The goal of this work was to evaluate the long-term efficacy of two dose-fractionation schedules for radiotherapy of calcaneodynia.Between February 2006 and February 2010, 457 evaluable patients were recruited for this prospective trial. All patients received orthovoltage radiotherapy. One course consisted of 6 fractions/3 weeks. In case of insufficient remission of pain after 6 weeks a second series was performed. Patients were randomly assigned to receive either single doses of 0.5 or 1.0 Gy. Endpoint was pain reduction. Pain was measured before, right after (early response), 6 weeks (delayed response), and approximately 2.5 years after radiotherapy (long-term response) with a questionnaire-based visual analogue scale (VAS) and a comprehensive pain score (CPS).The median follow-up was 32 months (range 9-57 months). The overall early, delayed, and long-term response rates for all patients were 87, 88, and 95%. The mean VAS values before treatment, for early, delayed, and long-term response for the 0.5 and 1.0 Gy groups were 65.5 ± 22.1 and 64.0 ± 20.5 (p = 0.19), 34.8 ± 24.7 and 39.0 ± 26.3 (p = 0.12), 25.1 ± 26.8 and 28.9 ± 26.8 (p = 0.16), and 16.3 ± 24.3 and 14.1 ± 19.7 (p = 0.68). The mean CPS values before treatment, for early, delayed, and log-term response were 10.1 ± 2.7 and 10.0 ± 3.0 (p = 0.78), 5.6 ± 3.7 and 6.0 ± 3.9 (p = 0.34), 4.0 ± 4.1 and 4.3 ± 3.6 (p = 0.26), and 2.1 ± 3.3 and 2.3 ± 3.2 (p = 0.34), respectively. No significant differences in long-term response quality between the two arms were found (p = 0.50).Radiotherapy is a very effective treatment for the management of benign calcaneodynia. For radiation protection reasons, the dose for a RT series should not exceed 3.0 Gy.
EVALuna2:18187

Radiotherapy for the elderly Patient with Head and Neck Squamous Cell Carcinoma - Experience of a Center for ENT-Tumors - Winkler, Leah-Sophie; Lettmaier, Sebastian; Semrau, Sabine; Mueller, Sarina K.; Traxdorf, Maximilian; Iro, Heinrich; Kesting, Marco Rainer; Fietkau, Rainer; Haderlein, Marlen (STRAHLENTHERAPIE UND ONKOLOGIE, 2021)
CRIS-Team WoS Importer:2021-07-16

Radiotherapy-induced changes in the systemic immune and inflammation parameters of head and neck cancer patients - Balazs, Katalin; Kis, Eniko; Badie, Christophe; Bogdandi, Eniko Noemi; Candeias, Serge; Garcia, Lourdes Cruz; Dominczyk, Iwona; Frey, Benjamin; Gaipl, Udo; Juranyi, Zsolt; Kocsis, Zsuzsa S.; Rutten, Eric Andreas; et al. (Cancers, 2019)
Though radiotherapy is a local therapy, it has systemic effects mainly influencing immune and inflammation processes. This has important consequences in the long-term prognosis and therapy individualization. Our objective was to investigate immune and inflammation-related changes in the peripheral blood of head and neck cancer patients treated with radiotherapy. Peripheral blood cells, plasma and blood cell-derived RNA were isolated from 23 patients before and at two time points after radiotherapy and cellular immune parameters, plasma protein changes and gene expression alterations were studied. Increased regulatory T cells and increased CTLA4 and PD-1 expression on CD4 cells indicated an immune suppression induced by the malignant condition, which was accentuated by radiotherapy. Circulating dendritic cells were strongly elevated before treatment and were not affected by radiotherapy. Decreased endoglin levels in the plasma of patients before treatment were further decreased by radiotherapy. Expression of the FXDR, SESN1, GADD45, DDB2 and MDM2 radiation-response genes were altered in the peripheral blood cells of patients after radiotherapy. All changes were long-lasting, detectable one month after radiotherapy. In conclusion we demonstrated radiotherapy-induced changes in systemic immune parameters of head and neck cancer patients and proposed markers suitable for patient stratification worth investigating in larger patient cohorts.
CRIS-Team Scopus Importer:2019-10-25
Keywords: Dendritic cell; Gene expression; Head and neck cancer; Immune phenotyping; Natural killer cell; PBMC; Plasma proteins; Radiotherapy; Regulatory T cell

Radiotherapy with paclitaxel/cisplatin vs. fluorouracil/cisplatin for head and neck cancer - Fietkau, Rainer; Hecht, Markus; Hofner, Benjamin; Iro, Heinrich; Gefeller, Olaf; Roedel, C.; Hautmann, M.; Koelbl, O.; Salay, A.; Ruebe, C.; Breinl, P.; Krings, W.; et al. (RADIOTHERAPY AND ONCOLOGY, 2019)
CRIS-Team WoS Importer:2019-06-18

RAD-ON01 study: modulation of the peripheral immune system following a sequential radon spa therapy - Rühle, Paul-Friedrich; Kullmann, M.; Frey, Benjamin; Klein, G.; Fournier, Claudia; Fietkau, Rainer; Gaipl, Udo; Deloch, Lisa (2017)
EVALuna2:32893

Radon affects Immune Cells ex vivo as well as in vivo in an Animal Model of experimental Arthritis - Deloch, Lisa; Rückert, Michael; Maier, A.; Hinrichs, A.; Flohr, Ann-Sophie; Eckert, D.; Seeling, Michaela; Nimmerjahn, Falk; Fietkau, Rainer; Fournier, C.; Frey, Benjamin; Gaipl, Udo (STRAHLENTHERAPIE UND ONKOLOGIE, 2021)
CRIS-Team WoS Importer:2021-07-16

Radon exposure—therapeutic effect and cancer risk - Maier, Andreas; Wiedemann, Julia; Rapp, Felicitas; Papenfuß, Franziska; Rödel, Franz; Hehlgans, Stephanie; Gaipl, Udo; Kraft, Gerhard; Fournier, Claudia; Frey, Benjamin (International Journal of Molecular Sciences, 2021)
Largely unnoticed, all life on earth is constantly exposed to low levels of ionizing radia-tion. Radon, an imperceptible natural occurring radioactive noble gas, contributes as the largest sin-gle fraction to radiation exposure from natural sources. For that reason, radon represents a major issue for radiation protection. Nevertheless, radon is also applied for the therapy of inflammatory and degenerative diseases in galleries and spas to many thousand patients a year. In either case, chronic environmental exposure or therapy, the effect of radon on the organism exposed is still under investigation at all levels of interaction. This includes the physical stage of diffusion and energy deposition by radioactive decay of radon and its progeny and the biological stage of initiating and propagating a physiologic response or inducing cancer after chronic exposure. The purpose of this manuscript is to comprehensively review the current knowledge of radon and its progeny on physical background, associated cancer risk and potential therapeutic effects.
CRIS-Team Scopus Importer:2021-01-15
Keywords: Anti-inflammatory effects; Changes immune activation; Clinical studies; Low doses; Osteoimmunological changes; Radon therapy; α-particles

Radon Improves Clinical Response in an Animal Model of Rheumatoid Arthritis Accompanied by Increased Numbers of Peripheral Blood B Cells and Interleukin-5 Concentration - Deloch, Lisa; Hehlgans, Stephanie; Rückert, Michael; Maier, Andreas; Hinrichs, Annika; Flohr, Ann-Sophie; Eckert, Denise; Weissmann, Thomas; Seeling, Michaela; Nimmerjahn, Falk; Fietkau, Rainer; Rödel, Franz; et al. (Cells, 2022)
Radon treatment is used as an established therapy option in chronic painful inflammatory diseases. While analgesic effects are well described, little is known about the underlying molecular effects. Among the suspected mechanisms are modulations of the anti-oxidative and the immune system. Therefore, we aimed for the first time to examine the beneficial effects of radon exposure on clinical outcome as well as the underlying mechanisms by utilizing a holistic approach in a controlled environment of a radon chamber with an animal model: K/BxN serum-induced arthritic mice as well as isolated cells were exposed to sham or radon irradiation. The effects on the anti-oxidative and the immune system were analyzed by flow-cytometry, qPCR or ELISA. We found a significantly improved clinical disease progression score in the mice, alongside significant increase of peripheral blood B cells and IL-5. No significant alterations were visible in the anti-oxidative system or regarding cell death. We conclude that neither cell death nor anti-oxidative systems are responsible for the beneficial effects of radon exposure in our preclinical model. Rather, radon slightly affects the immune system. However, more research is still needed in order to fully understand radon-mediated effects and to carry out reasonable risk-benefit considerations.
CRIS-Team Scopus Importer:2022-02-25
Keywords: Anti-oxidative system; B cells; Immune system; Inflammation; Macrophages; Monocytes; Radon therapy; Rheumatoid arthritis; Serum transfer arthritis; T cells

Randomized phase 2 trial of chemoradiotherapy plus induction or consolidation chemotherapy as total neoadjuvant therapy for locally advanced rectal cancer: CAO/ARO/AIO-12 - Hofheinz, R.; Fokas, E.; Allgaeuer, M.; Polat, B.; Klautke, G.; Grabenbauer, G.; Fietkau, Rainer; Kuhnt, T.; Staib, L.; Brunner, T.; Grosu, A.; Schmiegel, W.; et al. (ANNALS OF ONCOLOGY, 2019)
CRIS-Team WoS Importer:2019-08-09

Randomized phase-III-trial of concurrent chemoradiation for locally advanced head and neck cancer comparing dose reduced radiotherapy with paclitaxel/cisplatin to standard radiotherapy with fluorouracil/cisplatin: The PacCis-trial - Fietkau, Rainer; Hecht, Markus; Hofner, Benjamin; Lubgan, Dorota; Iro, Heinrich; Gefeller, Olaf; Rödel, Claus; Hautmann, Matthias G.; Kölbl, Oliver; Salay, Attila; Rübe, Christian; Melchior, Patrick; et al. (Radiotherapy and Oncology, 2020)
Background and purpose: This multicenter, phase 3 trial investigates whether the incorporation of concurrent paclitaxel and cisplatin together with a reduced total dose of radiotherapy is superior to standard fluorouracil–cisplatin based CRT. Materials and methods: Patients with SCCHN, stage III–IVB, were randomized to receive paclitaxel/cisplatin (PacCis)–CRT (arm A; paclitaxel 20 mg/m2 on days 2, 5, 8, 11 and 25, 30, 33, 36; cisplatin 20 mg/m2, days 1–4 and 29–32; RT to a total dose of 63.6 Gy) or fluorouracil/cisplatin (CisFU)–CRT (arm B; fluorouracil 600 mg/m2; cisplatin 20 mg/m2, days 1–5 and 29–33; RT: 70.6 Gy). Endpoint was 3-year-disease free survival (3y-DFS). Results: A total of 221 patients were enrolled between 2010 and 2015. With a median follow-up of 3.7 years, 3y-DFS in the CisFU arm and PacCis arm was 58.2% and 48.4%, respectively (HR 0.82, 95% CI 0.56–1.21, p = 0.52). The 3y-OS amounted to 64.6% in the CisFU arm, and to 59.2% in the PacCis arm (HR 0.82, 95% CI 0.54–1.24, p = 0.43). In the subgroup of p16-positive oropharyngeal carcinomas, 3y-DFS and 3y-OS was 84.6% vs 83.9% (p = 0.653), and 92.3% vs. 83.5% (p = 0.76) in arm A and B, respectively. Grade 3–4 hematological toxicities were significantly reduced in arm A (anemia, p = 0.01; leukocytopenia, p = 0.003), whereas grade 3 infections were reduced in arm B (p = 0.01). Conclusion: Paclitaxel/cisplatin–CRT with a reduced RT-dose is not superior to standard fluorouracil/cisplatin–CRT. Subgroup analyses indicate that a reduced radiation dose seems to be sufficient for p16+ oropharyngeal cancer or non-smokers. Clinical trial information: NCT01126216; EudraCT Number 2005-003484-23.
CRIS-Team Scopus Importer:2020-02-14
Keywords: Chemoradiotherapy; Cisplatin; Fluorouracil; Head and neck cancer; Paclitaxel

Randomized Phase II Trial of Chemoradiotherapy Plus Induction or Consolidation Chemotherapy as Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer: CAO/ARO/AIO-12 - Fokas, Emmanouil; Allgäuer, Michael; Polat, Bülent; Klautke, Gunther; Grabenbauer, Gerhard G.; Fietkau, Rainer; Kuhnt, Thomas; Staib, Ludger; Brunner, Thomas; Grosu, Anca Ligia; Schmiegel, Wolff; Jacobasch, Lutz; et al. (Journal of Clinical Oncology, 2019)
PURPOSE: Total neoadjuvant therapy is a new paradigm for rectal cancer treatment. Optimal scheduling of preoperative chemoradiotherapy (CRT) and chemotherapy remains to be established. PATIENTS AND METHODS: We conducted a multicenter, randomized, phase II trial using a pick-the-winner design on the basis of the hypothesis of an increased pathologic complete response (pCR) of 25% after total neoadjuvant therapy compared with standard 15% after preoperative CRT. Patients with stage II or III rectal cancer were assigned to group A for induction chemotherapy using three cycles of fluorouracil, leucovorin, and oxaliplatin before fluorouracil/oxaliplatin CRT (50.4 Gy) or to group B for consolidation chemotherapy after CRT. Secondary end points included toxicity, compliance, and surgical morbidity. RESULTS: Of the 311 patients enrolled, 306 patients were evaluable (156 in group A and 150 in group B). CRT-related grade 3 or 4 toxicity was lower (37% v 27%) and compliance with CRT higher in group B (91%, 78%, and 76% v 97%, 87%, and 93% received full-dose radiotherapy, concomitant fluorouracil, and concomitant oxaliplatin in groups A and B, respectively); 92% versus 85% completed all induction/consolidation chemotherapy cycles, respectively. The longer interval between completion of CRT and surgery in group B (median 90 v 45 days in group A) did not increase surgical morbidity. A pCR in the intention-to-treat population was achieved in 17% in group A and in 25% in group B. Thus, only group B (P < .001), but not group A (P = .210), fulfilled the predefined statistical hypothesis. CONCLUSION: Up-front CRT followed by chemotherapy resulted in better compliance with CRT but worse compliance with chemotherapy compared with group A. Long-term follow-up will assess whether improved pCR in group B translates to better oncologic outcome.
CRIS-Team Scopus Importer:2019-12-10

Rare frameshift mutation in SERPINA3 contributes to generalized pustular psoriasis - Hüffmeier, Ulrike; Sticht, Heinrich; Wenzel, J.; Wilsmann-Theis, D.; Wolff, K.; Löhr, Sabine; Frey, Benjamin; Hahn, M.; Ekici, Arif Bülent; Uebe, S.; Thiel, Christian; Wiesmann da Silva Reis, André; et al. (EUROPEAN JOURNAL OF HUMAN GENETICS, 2019)
CRIS-Team WoS Importer:2019-10-25

Rare Loss-of-Function Mutation in SERPINA3 in Generalized Pustular Psoriasis - Frey, Silke; Sticht, Heinrich; Wilsmann-Theis, Dagmar; Gerschütz, Anne; Wolf, Katharina; Löhr, Sabine; Haskamp, Stefan; Frey, Benjamin; Hahn, Madelaine; Ekici, Arif Bülent; Uebe, Steffen; Thiel, Christian; et al. (Journal of Investigative Dermatology, 2020)
CRIS-Team Scopus Importer:2020-03-06

Rate of individuals with clearly increased radiosensitivity rise with age both in healthy individuals and in cancer patients - Schuster, Barbara; Ellmann, Anna; Mayo, Theresa; Auer, Judith; Haas, Matthias; Hecht, Markus; Fietkau, Rainer; Distel, Luitpold (BMC Geriatrics, 2018)
BACKGROUND: The question of an age dependence of individual radiosensitivity has only marginally been studied so far. Therefore, we analyzed blood samples of healthy individuals and cancer patients of different ages to determine individual radiosensitivity. METHODS: Ex vivo irradiated blood samples of 595 individuals were tested. Chromosomes 1, 2 and 4 were stained by 3-color fluorescence in situ hybridization and aberrations were analyzed. Radiosensitivity was determined by the mean breaks per metaphase (B/M). RESULTS: Healthy individuals (mean age 50.7 years) had an average B/M value of 0.42 ± 0.104 and an increase of 0.0014B/M per year. The patients (mean age 60.4 years) had an average B/M value of 0.44 ± 0.150 and radiosensitivity did not change with age. In previous studies we found that from a value of 0.6B/M on an individual is considered to be distinctly radiosensitive. The portion of radiosensitive individuals (B/M > 0.6) increased in both cohorts with age. CONCLUSION: Individual radiosensitivity rises continuously with age, yet with strong interindividual variation. No age related increase of radiosensitivity can be demonstrated in patients due to the strong interindividual variation. However among old cancer patients there is a higher probability to have patients with clearly increased radiosensitivity than at younger age.
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Reactivation of HCMV during RT of the brain results in critical illness and early mortality - Frey, Benjamin; Goerig, Nicole; Becker, Ina; Donaubauer, Anna-Jasmina; Korn, Klaus; Überla, Klaus; Schmidt, Manuel; Dörfler, Arnd; Engelhorn, Tobias; Eyüpoglu, Ilker Yasin; Putz, Florian; Semrau, Sabine; et al. (RADIOTHERAPY AND ONCOLOGY, 2020)
CRIS-Team WoS Importer:2021-06-18

Real-Time Respiratory Motion Analysis Using 4-D Shape Priors - Wasza, Jakob; Fischer, Peter; Leutheuser, Heike; Oefner, Tobias; Bert, Christoph; Maier, Andreas; Hornegger, Joachim (IEEE Transactions on Biomedical Engineering, 2016)
Respiratory motion analysis based on range imaging (RI) has emerged as a popular means of generating respiration surrogates to guide motion management strategies in computer-assisted interventions. However, existing approaches employ heuristics, require substantial manual interaction, or yield highly redundant information. In this paper, we propose a framework that uses preprocedurally obtained 4-D shape priors from patient-specific breathing patterns to drive intraprocedural RI-based real-time respiratory motion analysis. As the first contribution, we present a shape motion model enabling an unsupervised decomposition of respiration induced high-dimensional body surface displacement fields into a low-dimensional representation encoding thoracic and abdominal breathing. Second, we propose a method designed for GPU architectures to quickly and robustly align our models to high-coverage multiview RI body surface data. With our fully automatic method, we obtain respiration surrogates yielding a Pearson correlation coefficient (PCC) of 0.98 with conventional surrogates based on manually selected regions on RI body surface data. Compared to impedance pneumography as a respiration signal that measures the change of lung volume, we obtain a PCC of 0.96. Using off-the-shelf hardware, our framework enables high temporal resolution respiration analysis at 50 Hz.
Keywords: Graphics processing unit (GPU); radiation therapy; range imaging (RI); respiratory motion

Recent advanced in Surface Guided Radiation Therapy - Freislederer, P.; Kügele, M.; Öllers, M.; Swinnen, A.; Sauer, Tim-Oliver; Bert, Christoph; Giantsoudi, D.; Corradini, S.; Batista, V. (Radiation Oncology, 2020)
The growing acceptance and recognition of Surface Guided Radiation Therapy (SGRT) as a promising imaging technique has supported its recent spread in a large number of radiation oncology facilities. Although this technology is not new, many aspects of it have only recently been exploited. This review focuses on the latest SGRT developments, both in the field of general clinical applications and special techniques.SGRT has a wide range of applications, including patient positioning with real-time feedback, patient monitoring throughout the treatment fraction, and motion management (as beam-gating in free-breathing or deep-inspiration breath-hold). Special radiotherapy modalities such as accelerated partial breast irradiation, particle radiotherapy, and pediatrics are the most recent SGRT developments.The fact that SGRT is nowadays used at various body sites has resulted in the need to adapt SGRT workflows to each body site. Current SGRT applications range from traditional breast irradiation, to thoracic, abdominal, or pelvic tumor sites, and include intracranial localizations.Following the latest SGRT applications and their specifications/requirements, a stricter quality assurance program needs to be ensured. Recent publications highlight the need to adapt quality assurance to the radiotherapy equipment type, SGRT technology, anatomic treatment sites, and clinical workflows, which results in a complex and extensive set of tests.Moreover, this review gives an outlook on the leading research trends. In particular, the potential to use deformable surfaces as motion surrogates, to use SGRT to detect anatomical variations along the treatment course, and to help in the establishment of personalized patient treatment (optimized margins and motion management strategies) are increasingly important research topics. SGRT is also emerging in the field of patient safety and integrates measures to reduce common radiotherapeutic risk events (e.g. facial and treatment accessories recognition).This review covers the latest clinical practices of SGRT and provides an outlook on potential applications of this imaging technique. It is intended to provide guidance for new users during the implementation, while triggering experienced users to further explore SGRT applications.
CRIS-Team Scopus Importer:2020-08-14
Keywords: Deep-inspiration breath-hold; Intra-fractional motion mitigation; Motion management; Patient positioning; Patient safety; SGRT; Surface guided radiation therapy

Recurrent glioblastoma: who receives tumor specific treatment and how often? - Steffens, Rieke; Semrau, Sabine; Lahmer, Godehard; Putz, Florian; Lettmaier, Sebastian; Eyüpoglu, Ilker Yasin; Buchfelder, Michael; Fietkau, Rainer (Journal of Neuro-Oncology, 2016)
The recurrence of glioblastoma (rGBM) is inevitable and often short-term. Therefore, information on the prognosis and effectiveness of tumor-specific versus purely palliative approaches should be more in-depth than a mere list of available treatment options for patients in this situation. However, follow-up data on the course of the disease in unselected patient populations after completion of primary treatment are scarce. This single-center analysis investigated the rate and number of glioblastoma recurrences after initial radiotherapy in 189 consecutive GM patients, focusing on the incidence of early death and the frequency of tumor-specific treatment (TST) versus best-supportive care (BSC) as well as the outcomes for the different approaches. In 61 % of initial population first recurrence (rGBM) could be determined by histology or imaging. 47 % received TST. 58 % of the patients with rGBM and TST were diagnosed with a second recurrence. Up to five recurrences were treated. 35-45 % of patients died before undergoing imaging studies to confirm the next recurrence. Multivariate analysis identified male sex and KPS score as independent factors (p < 0.01) for the choice of TST over BSC. Median overall survival from the diagnosis of first recurrence was 267 days in the TST group versus 65 days in patients receiving BSC (p < 0.0001). Nearly half of all rGBM patients received second-line TST, but a remarkably high proportion died early. Gender and KPS played a role in the choice of TST over BSC for recurrence treatment.
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Reducing contrast contamination in radial turbo-spin-echo acquisitions by combining a narrow-band KWIC filter with parallel imaging - Neumann, Daniel; Breuer, Felix A.; Voelker, Michael; Brandt, Tobias; Griswold, Mark A.; Jakob, Peter M.; Blaimer, Martin (Magnetic Resonance in Medicine, 2014)
Cartesian turbo spin-echo (TSE) and radial TSE images are usually reconstructed by assembling data containing different contrast information into a single k-space. This approach results in mixed contrast contributions in the images, which may reduce their diagnostic value. The goal of this work is to improve the image contrast from radial TSE acquisitions by reducing the contribution of signals with undesired contrast information.Radial TSE acquisitions allow the reconstruction of multiple images with different T2 contrasts using the k-space weighted image contrast (KWIC) filter. In this work, the image contrast is improved by reducing the band-width of the KWIC filter. Data for the reconstruction of a single image are selected from within a small temporal range around the desired echo time. The resulting dataset is undersampled and, therefore, an iterative parallel imaging algorithm is applied to remove aliasing artifacts.Radial TSE images of the human brain reconstructed with the proposed method show an improved contrast when compared with Cartesian TSE images or radial TSE images with conventional KWIC reconstructions.The proposed method provides multi-contrast images from radial TSE data with contrasts similar to multi spin-echo images. Contaminations from unwanted contrast weightings are strongly reduced.
EVALuna2:18272

Reduction of elective radiotherapy treatment volume in definitive treatment of locally advanced head and neck cancer—comparison of a prospective trial with a revised simulated contouring approach - Weissmann, Thomas; Speer, Stefan; Putz, Florian; Lettmaier, Sebastian; Schubert, Philipp; Shariff, Maya; Semrau, Sabine; Gostian, Antoniu-Oreste; Traxdorf, Maximilian; Mueller, Sarina K.; Eckstein, Markus; Hautmann, Matthias; et al. (Journal of Clinical Medicine, 2021)
Definitive radiochemotherapy of locally advanced head and neck squamous cell cancer (HNSCC) achieves high locoregional tumor control rates; but is frequently associated with long-term toxicity. A future direction could be a de-escalation strategy focusing on treated volume rather than radiotherapy dose. This analysis evaluates radiotherapy dose and volume parameters of patients treated with a standard contouring approach in a clinical trial context compared with a revised volume-reduced contouring approach. In this case, 30 consecutive patients from the CheckRad-CD8 trial treated at a single study center were included in this analysis. Treatment toxicity and quality of life were assessed at the end of radiotherapy. Standard treatment plans (ST) following state of the art contouring guidelines that were used for patient treatment and volume reduced treatment plans (VRT) according to a revised simulated approach were calculated for each patient. Planning target volumes (PTV) and mean doses to 38 organs-at-risk structures were compared. At the end of radiotherapy patients reported high rates of mucositis; dysphagia and xerostomia. In addition; patient reported quality of life as assessed by the EORTC QLQ-HN35 questionnaire deteriorated. Comparing the two contouring approaches; the elective PTV_56 Gy and the high risk PTV_63 Gy (shrinking field) were significantly smaller in the VRT group. Significant reduction of mean dose to structures of the oral cavity; the larynx as well as part of the swallowing muscles and the submandibular glands was achieved in the simulated VRT-plan. Treatment de-intensification by reduction of the irradiated volume could potentially reduce treatment volume and mean doses to organs at risk. The proposed contouring approach should be studied further in the context of a clinical trial.
CRIS-Team Scopus Importer:2021-10-22
Keywords: De-intensification; Definitive treatment; Head neck cancer; Radiotherapy; Salivary glands; Swallowing function; Volume reduc-tion

Regional deep hyperthermia: impact of observer variability in CT-based manual tissue segmentation on simulated temperature distribution - Aklan, Bassim; Hartmann, Josefin; Zink, Diana; Siavooshhaghighi, Hadi; Merten, Ricarda; Putz, Florian; Ott, Oliver; Fietkau, Rainer; Bert, Christoph (Physics in Medicine and Biology, 2017)
The aim of this study was to systematically investigate the influence of the inter- and intra-observer segmentation variation of tumors and organs at risk on the simulated temperature coverage of the target. CT scans of six patients with tumors in the pelvic region acquired for radiotherapy treatment planning were used for hyperthermia treatment planning. To study the effect of inter-observer variation, three observers manually segmented in the CT images of each patient the following structures: fat, muscle, bone and the bladder. The gross tumor volumes (GTV) were contoured by three radiation oncology residents and used as the hyperthermia target volumes. For intra-observer variation, one of the observers of each group contoured the structures of each patient three times with a time span of one week between the segmentations. Moreover, the impact of segmentation variations in organs at risk (OARs) between the three inter-observers was investigated on simulated temperature distributions using only one GTV. The spatial overlap between individual segmentations was assessed by the Dice similarity coefficient (DSC) and the mean surface distance (MSD). Additionally, the temperatures T90/T10 delivered to 90%/10% of the GTV, respectively, were assessed for each observer combination. The results of the segmentation similarity evaluation showed that the DSC of the inter-observer variation of fat, muscle, the bladder, bone and the target was 0.68 ± 0.12, 0.88 ± 0.05, 0.73 ± 0.14, 0.91 ± 0.04 and 0.64 ± 0.11, respectively. Similar results were found for the intra-observer variation. The MSD results were similar to the DSCs for both observer variations. A statistically significant difference (p < 0.05) was found for T90 and T10 in the predicted target temperature due to the observer variability. The conclusion is that intra- and inter-observer variations have a significant impact on the temperature coverage of the target. Furthermore, OARs, such as bone and the bladder, may essentially influence the homogeneity of the simulated target temperature distribution.
EVALuna2:32876

Regional hyperthermia with cisplatin added to gemcitabine versus gemcitabine in patients with resected pancreatic ductal adenocarcinoma: The HEAT randomised clinical trial - Issels, Rolf D.; Boeck, Stefan; Pelzer, Uwe; Mansmann, Ulrich; Ghadjar, Pirus; Lindner, Lars H.; Albertsmeier, Markus; Angele, Martin K.; Schmidt, Michael; Xu, Yujun; Bahra, Marcus; Pratschke, Johann; et al. (European Journal of Cancer, 2023)
Background: Regional hyperthermia (RHT) with cisplatin added to gemcitabine showed efficacy in gemcitabine-pre-treated patients with advanced pancreatic ductal adenocarcinoma. We conducted a randomised clinical trial to investigate RHT with cisplatin added to gemcitabine (GPH) compared with gemcitabine (G) in the adjuvant setting of resected pancreatic ductal adenocarcinoma. Methods: This randomised, multicentre, open-label trial randomly assigned patients to either GPH (gemcitabine 1000 mg/m2 on day 1, 15 and cisplatin 25 mg/m2 with RHT on day 2, 3 and 15,16) or to G (gemcitabine 1000 mg/m2 on day 1,8,15), four-weekly over six cycles. Disease-free survival (DFS) was the primary end-point. Secondary end-points included overall survival (OS) and safety. Results: A total of 117 eligible patients (median age, 63 years) were randomly allocated to treatment (57 GPH; 60 G). With a follow-up time of 56.6 months, the median DFS was 12.7 compared to 11.2 months for GPH and G, respectively (p = 0.394). Median post-recurrence survival was significantly prolonged in the GPH-group (15.3 versus 9.8 months; p = 0.031). Median OS reached 33.2 versus 25.2 months (p = 0.099) with 5-year survival rates of 28.4% versus 18.7%. Excluding eight patients who received additional capecitabine in the G-arm (investigators choice), median OS favoured GPH (p = 0.052). Adverse events CTCAE (Common Terminology Criteria for Adverse Events) grade ≥3 occurred in 61.5% (GPH) versus 63.6% (G) of patients. Two patients in the G-group died because of treatment-related toxic effects. Conclusions: The randomised controlled Hyperthermia European Adjuvant Trial study failed to demonstrate a significant difference in DFS. However, it suggests a difference in post-recurrence survival and a trend for improved OS. ClinicalTrials: gov, number NCT01077427.
CRIS-Team Scopus Importer:2023-01-27
Keywords: Adjuvant chemotherapy; Cisplatin; Gemcitabine; HEAT study; Pancreatic cancer; Randomised clinical trial; Regional hyperthermia

Region of interest optimization for radiation therapy of breast cancer - Sauer, Tim-Oliver; Ott, Oliver; Lahmer, Godehard; Fietkau, Rainer; Bert, Christoph (Journal of Applied Clinical Medical Physics, 2021)
Purpose: The goal of this study was to investigate how the choice of the region of interest (ROI) affects the registration results of surface imaging for daily positioning of breast cancer patients. Methods: The AlignRT system (VisionRT, London) and the XVI Cone beam CT (CBCT; Elekta, Stockholm) installed on two Versa HD linacs (Elekta) were used in this study, which included 28 patients (160 fractions). In the clinical workflow, patients were prepositioned with AlignRT and then shifted in 6 degrees of freedom (DOF) according to the CBCT. A new reference capture was taken immediately afterward. Retrospectively, the surface capture resulting from prepositioning was registered to the latest reference capture. By varying the ROI used for registration, the surface-based results were optimized in terms of minimizing the deviation to the clinically applied CBCT shifts. Two sets of ROIs were used: one obtained by applying a variable margin to the breast surface, another by combining ROIs of anatomical structures, including the sternum and contralateral breast. Results: Registration results showed significant differences from one ROI to another. Generally, the results improved with increasing ROI size, especially for rotational DOFs. ROIs, including the axilla or supraclavicular lymph drainage region, did not yield an improved registration result. On the other hand, an ROI comprising the breast surface, sternum, and a belt caudal to the breasts decreased the average magnitude of the translational and rotational deviations by 6.6% and 30.8% (p < 0.01), respectively, compared to the breast surface only results. Conclusion: The influence of the ROI choice on surface imaging registration results was analyzed and the surface-based shifts were compared to clinically applied CBCT shifts. An optimal ROI for the treatment of breast cancer patients, consisting of the breast surface, sternum, and a belt, was identified.
CRIS-Team Scopus Importer:2021-10-01
Keywords: breast cancer; radiation therapy; surface guided radiation therapy

Regulatory T cells and cytotoxic T cells close to the epithelial–stromal interface are associated with a favorable prognosis - Rudolf, Julian; Büttner-Herold, Maike; Erlenbach-Wuensch, Katharina; Posselt, Rebecca; Jeßberger, Jonas; Haderlein, Marlen; Hecht, Markus; Hartmann, Arndt; Fietkau, Rainer; Distel, Luitpold (OncoImmunology, 2020)
Cytotoxic T cells and regulatory T cells play a crucial role in the outcome of cancer patients. Besides the density of these cells, it was shown recently that the spatial distribution is equally important. Here, we specifically analyzed the spatial distribution of these T cell subtypes at the epithelial–stromal interface in a rectal cancer cohort and its relevance for prognosis. We studied a cohort of 191 patients with advanced rectal cancer treated by radiochemotherapy (RCT). Tissue microarrays were immunohistochemical double-stained by FoxP3+ and CD+. Cell densities were analyzed in the stromal and epithelial compartment. Additionally, an image analysis software calculated the distances of lymphocytes to the epithelial–stromal interface (ESI). CD8+ and FoxP3+ cell counts decreased clearly after RCT with the decrease of FoxP3+ being more pronounced than of CD8+ cells. In the invasive front, short distances of the ESI to CD8+ and to FoxP3+ cells were associated with improved overall survival. Cell counts in the stromal compartment had no influence on prognosis. No correlation between stromal and epithelial lymphocyte densities was observed. The distance of epithelial–stromal interface to CD8+ and FoxP3+ cells was more accurate in predicting prognosis in the stromal compartment of rectal cancer patients than mere cell counts and could thereby be means of better stratifying patients for therapy. This observation will have to be validated in future prospective studies with regard to other tumor entities and its implications for the responsiveness of tumors to new therapeutic modalities.
CRIS-Team Scopus Importer:2020-04-28
Keywords: epithelial–stromal interface; rectal cancer; regulatory T cells; spatial distribution; ﻿cytotoxic T cells

Regulatory T cells protect from local and systemic bone destruction in arthritis. - Zaiss, Mario; Frey, Benjamin; Heß, Andreas; Zwerina, Jochen; Luther, Julia; Nimmerjahn, Falk; Engelke, Klaus; Kollias, George; Huenig, Thomas; Schett, Georg; David, Jean-Pierre (Journal of Immunology, 2010)
We previously demonstrated the suppressive effects of regulatory T cells (Treg cells) on osteoclast differentiation in vitro. In this article, we show that blood markers of bone resorption inversely correlate with the amount of circulating Treg cells in healthy controls and rheumatoid arthritis patients, further suggesting that Treg cells may control bone destruction in vivo. Indeed, bone marrow from Foxp3-transgenic (Foxp3tg) mice fully protected human TNF transgenic (hTNFtg) mice from TNF-alpha-induced bone destruction, whereas Foxp3-deficient bone marrow enhanced local and systemic bone loss. The same protective effect was also obtained by treating hTNFtg mice with the CD28 superagonist mAb (CD28 SA), which increased Treg cell numbers. In both models, bone protection by Treg cells was associated with reduced osteoclast numbers, resulting in less bone-resorbing activity. Reduced osteoclast numbers were not caused by an intrinsic defect in osteoclast differentiation because osteoclast precursors from hTNFtg/Foxp3tg chimeras responded normally to M-CSF and receptor activator of NF-kappaB ligand. Although a decrease in the clinical signs of arthritis was observed in Foxp3tg bone marrow-transferred and CD28 SA-treated hTNFtg mice, the bone-protective effect of Treg cells was independent of the suppression of inflammation, as demonstrated by the increased systemic bone density observed in wild-type mice treated with CD28 SA. This work demonstrated that increasing Treg cell numbers improved clinical signs of arthritis and suppressed local and systemic bone destruction. Thus, enhancing the activity of Treg cells would be beneficial for the treatment of inflammation-induced bone loss observed in rheumatoid arthritis.

Re-Irradiation for Patients with Head and Neck Squamous Cell Carcinoma - A multicenter Analysis of 253 Patients of the jDEGRO Trial Group - Roesch, Johannes; Oertel, M.; Dobiasch, S.; Fabian, A.; Fleischmann, D.; Von Der Gruen, J.; Hering, D.; Hess, S.; Hoeck, M.; Kaesmann, L.; Loeser, A.; Maeurer, M.; et al. (STRAHLENTHERAPIE UND ONKOLOGIE, 2021)
CRIS-Team WoS Importer:2021-07-16

Reirradiation for recurrent head and neck cancer with salvage interstitial pulsed-dose-rate brachytherapy: Long-term results - Strnad, Vratislav; Lotter, Michael; Kreppner, Stephan; Fietkau, Rainer (Strahlentherapie und Onkologie, 2015)
To assess the long-term results of protocol-based interstitial pulsed-dose-rate (PDR) brachytherapy as reirradiation combined with simultaneous chemotherapy and interstitial hyperthermia in selected patients with recurrent head and neck tumors.A total of 104 patients with biopsy-proven recurrent head and neck cancer were treated with interstitial PDR brachytherapy. Salvage surgery had also been undergone by 53/104 (51%) patients (R1 or R2 resection in > 80% of patients). Salvage brachytherapy alone was administered in 81 patients (78%), with a median total dose of 56.7 Gy. Salvage brachytherapy in combination with external beam radiotherapy (EBRT) was performed in 23/104 patients (32%), using a median total dose of DREF = 24 Gy. Simultaneously to PDR brachytherapy, concomitant chemotherapy was administered in 58/104 (55.8%) patients. A single session of interstitial hyperthermia was also used to treat 33/104 (31.7%) patients. The analysis was performed after a median follow-up of 60 months.Calculated according to Kaplan-Meier, local tumor control rates after 2, 5, and 10 years were 92.5, 82.4, and 58.9%, respectively. Comparing results of salvage PDR brachytherapy with or without simultaneous chemotherapy, the 10-year local control rates were 76 vs. 39% (p = 0014), respectively. No other patient- or treatment-related parameters had a significant influence on treatment results. Soft tissue necrosis or bone necrosis developed in 18/104 (17.3%) and 11/104 (9.6%) patients, respectively, but only 3% of patients required surgical treatment.PDR interstitial brachytherapy with simultaneous chemotherapy is a very effective and, in experienced hands, also a safe treatment modality in selected patients with head and neck cancer in previously irradiated areas.
EVALuna2:18289

Re-Irradiation in head & neck cancer - a pooled analysis of 253 individual cases - Roesch, Johannes; Oertel, M.; Fabian, A.; Hoeck, M.; Von Der Gruen, J.; Loeser, A.; Suess, C.; Vinsensia, M.; Tamaskovics, B.; Hess, S.; Waltenberger, M.; Wegen, S.; et al. (RADIOTHERAPY AND ONCOLOGY, 2021)
CRIS-Team WoS Importer:2021-11-26

Reirradiation of recurent glioblastomas: High prognostic significance of contrast-enhancing tumor volume - Mansoorian, Sina; Coras, Roland; Weissmann, Thomas; Lettmaier, Sebastian; Semrau, Sabine; Frey, Benjamin; Bert, Christoph; Schmidt, M.; Fietkau, Rainer; Putz, Florian (STRAHLENTHERAPIE UND ONKOLOGIE, 2021)
CRIS-Team WoS Importer:2021-07-16

Re-irradiation of the chest wall for local breast cancer recurrence : Results of salvage brachytherapy with hyperthermia - Auoragh, A.; Strnad, Vratislav; Ott, O. J.; Beckmann, Matthias; Fietkau, Rainer (Strahlentherapie und Onkologie, 2016)
Following mastectomy and adjuvant external beam radiation therapy in patients with breast cancer, the incidence of local or locoregional recurrence is approximately 9 % (2-20 %). Alongside the often limited possibilities of surgical treatment, radiation therapy combined with superficial hyperthermia is the most effective local therapy. In the present work, a retrospective analysis of salvage brachytherapy combined with superficial hyperthermia for chest wall recurrences is presented.Between 2004 and 2011, 18 patients with a total of 23 target volumes resulting from chest wall recurrences after previously mastectomy and external beam radiation therapy (median 56 Gy, range 50-68 Gy) were treated with superficial brachytherapy as salvage treatment: 8 patients (44 %) had macroscopic tumor, 3 (17 %) had microscopic tumor (R1), and 7 (39 %) had undergone R0 resection and were treated due to risk factors. A dose of 50 Gy was given (high-dose rate [HDR] and pulsed-dose rate [PDR] procedures). In all, 5 of 23 patients (22 %) received additional concurrent chemotherapy, and in 20 of 23 (87 %) target volumes additional superficial hyperthermia was carried out twice weekly.The 5-year local recurrence-free survival was 56 %, the disease-free survival was 28 %, and a 5-year overall survival was 22 %. Late side effects Common Toxicity Criteria (CTC) grade 3 were reported in 17 % of the patients: 2 of 18 (11 %) had CTC grade 3 fibrosis, and 1 of 18 (6 %) had a chronic wound healing disorder.Re-irradiation as salvage brachytherapy with superficial hyperthermia for chest wall recurrences is a feasible and safe treatment with good local control results and acceptable late side effects.
EVALuna2:18364

Re-irradiation with interstitial pulsed-dose-rate brachytherapy for unresectable recurrent head and neck carcinoma - Strnad, Vratislav; Lotter, Michael; Kreppner, Stephan; Fietkau, Rainer (Brachytherapy, 2014)
To assess the long-term results of protocol-based interstitial pulsed-dose-rate (PDR) brachytherapy combined with simultaneous chemotherapy in selected patients with recurrent head and neck tumors not amenable to salvage surgery.A total of 51 patients with recurrent head and neck cancer were treated with interstitial PDR brachytherapy. Forty patients (78%) had salvage brachytherapy alone using a median total dose of 60 Gy. Salvage brachytherapy in combination with external beam therapy was performed in 11 patients (22%) using a median total dose of DREF=27 Gy. Simultaneously with the PDR brachytherapy, a concomitant chemotherapy was administered in 35/51 (69%) of patients. The analysis was performed after a median followup of 58 months.Local control rates calculated according to Kaplan-Meier after 2 and 5 years were 71% and 57%, respectively. Comparing results of salvage PDR brachytherapy with or without simultaneous chemotherapy, the 5-year local recurrence-free survival rates were 78.9% vs. 38.5% (p=0.01), respectively. No other patient or treatment-related parameters had a significant influence on treatment results. A total of 9/51 (17.7%) and 6/51 (11.8%) patients developed soft-tissue necrosis or bone necrosis, respectively, but only 2% of patients required surgical treatment.PDR interstitial brachytherapy with pulse doses between 0.4 and 0.7 Gy/h/24 h with simultaneous chemotherapy is an effective and safe option for curative therapy in selected patients with head and neck cancer in previously irradiated areas, which are not suitable for salvage surgery.
EVALuna2:18174

Relevance of the time interval between surgery and adjuvant radio (chemo) therapy in HPV-negative and advanced head and neck carcinoma of unknown primary (CUP) - Balk, Matthias; Rupp, Robin; Mantsopoulos, Konstantinos; Allner, Moritz; Grundtner, Philipp; Müller-Hübner, Sarina; Traxdorf, Maximilian; Eckstein, Markus; Speer, Stefan; Semrau, Sabine; Fietkau, Rainer; Iro, Heinrich; et al. (BMC Cancer, 2021)
Introduction In contrast to head and neck squamous cell carcinoma (HNSCC), the effect of treatment duration in HNSCC-CUP has not been thoroughly investigated. Thus, this study aimed to assess the impact of the time interval between surgery and adjuvant therapy on the oncologic outcome, in particular the 5-year overall survival rate (OS), in advanced stage, HPV-negative CUPs at a tertiary referral hospital. 5-year disease specific survival rate (DSS) and progression free survival rate (PFS) are defined as secondary objectives. Material and methods Between January 1st, 2007, and March 31st, 2020 a total of 131 patients with CUP were treated. Out of these, 59 patients with a confirmed negative p16 analysis were referred to a so-called CUP-panendoscopy with simultaneous unilateral neck dissection followed by adjuvant therapy. The cut-off between tumor removal and delivery of adjuvant therapy was set at the median, i.e. patients receiving adjuvant therapy below or above the median time interval. Results Depending on the median time interval of 55 days (d) (95% CI 51.42-84.52), 30 patients received adjuvant therapy within 55 d (mean 41.69 d, SD = 9.03) after surgery in contrast to 29 patients at least after 55 d (mean 73.21 d, SD = 19.16). All patients involved in the study were diagnosed in advanced tumor stages UICC III (n = 4; 6.8%), IVA (n = 27; 45.8%) and IVB (n = 28; 47.5%). Every patient was treated with curative neck dissection. Adjuvant chemo (immune) radiation was performed in 55 patients (93.2%), 4 patients (6.8%) underwent adjuvant radiation only. The mean follow-up time was 43.6 months (SD = 36.7 months). The 5-year OS rate for all patients involved was 71% (95% CI 0.55-0.86). For those patients receiving adjuvant therapy within 55 d (77, 95% CI 0.48-1.06) the OS rate was higher, yet not significantly different from those with delayed treatment (64, 95% CI 0.42-0.80; X-(1)(2) = 1.16, p = 0.281). Regarding all patients, the 5-year DSS rate was 86% (95% CI 0.75-0.96). Patients submitted to adjuvant treatment in less than 55 d the DSS rate was 95% (95% CI 0.89-1.01) compared to patients submitted to adjuvant treatment equal or later than 55 d (76% (95% CI 0.57-0.95; X-(1)(2) = 2.32, p = 0.128). The 5-year PFS rate of the entire cohort was 72% (95% CI 0.59-0.85). In the group < 55 d the PFS rate was 78% (95% CI 0.63-0.94) and thus not significantly different from 65% (95% CI 0.45-0.85) of the group >= 55 d; (X-(1)(2) = 0.29, p = 0.589). Conclusions The results presented suggest that the oncologic outcome of patients with advanced, HPV-negative CUP of the head and neck was not significantly affected by a prolonged period between surgery and adjuvant therapy. Nevertheless, oncologic outcome tends to be superior for early adjuvant therapy.
CRIS-Team WoS Importer:2021-12-03

Relevance of the time interval between surgery and adjuvant radio (chemo) therapy in HPV-negative and advanced head and neck carcinoma of unknown primary (CUP) - Balk, Matthias; Rupp, Robin; Mantsopoulos, Konstantinos; Allner, Moritz; Grundtner, Philipp; Mueller, Sarina K.; Traxdorf, Maximilian; Eckstein, Markus; Speer, Stefan; Semrau, Sabine; Fietkau, Rainer; Iro, Heinrich; et al. (ONCOLOGY RESEARCH AND TREATMENT, 2022)
CRIS-Team WoS Importer:2022-12-16

Reliability of determining the resectability of locally progressed pancreatic ductal adenocarcinomas - results from the CONKO-007 multicenter randomized controlled trial (EudraCT:2009-014476-21) - Wittel, U. A.; Golcher, H.; Gruetzmann, R.; Bechstein, W. O.; Belyaev, O.; Uhl, W.; Ghadimi, M.; Hopt, U.; Pirkl, A.; Lubgan, Dorota; Hohenberger, Werner; Oettle, H.; et al. (2018)
EVALuna2:36518

Renal denervation preserves renal function in patients with chronic kidney disease and resistant hypertension - Ott, Christian; Mahfoud, Felix; Schmid, Axel; Toennes, Stefan W.; Ewen, Sebastian; Ditting, Tilmann; Veelken, Roland; Ukena, Christian; Uder, Michael; Boehm, Michael; Schmieder, Roland (Journal of Hypertension, 2015)
Arterial hypertension and increased sympathetic activity are underlying pathogenetic mechanisms of the progressive loss of renal function in patients with chronic kidney disease (CKD). Meta-analyses have shown that impaired renal function is an independent cardiovascular risk factor. We hypothesized that renal denervation (RDN) decreases the decline of renal function in patients with CKD stages 3 and 4 and treatment-resistant hypertension.We performed an observational study of 27 patients with CKD stages 3 and 4, office blood pressure (BP) >= 140/90 mmHg, while on at least three antihypertensive drug classes including diuretic, and diagnosis confirmed by 24-h ambulatory BP measurement >= 130/80 mmHg. All patients underwent catheter-based RDN using the Symplicity Flex RDN System (Medtronic Inc., Santa Rosa, California, USA). Renal function was evaluated for up to 3 years prior and 1 year after RDN. The change in estimated glomerular filtration rate (eGFR) was calculated by regression slope individually for each patient before and after RDN. The study was registered at http://www.clinicaltrials.gov (ID: NCT01442883).Mean baseline BP was 156 ± 12/82 ± 13 mmHg, despite treatment with 6.2 ± 1.1 antihypertensive drugs. One year after RDN, office BP was reduced by 20 ± 20 (P < 0.001)/8 ± 14 mmHg (P = 0.005) and average 24-h ambulatory BP by 9 ± 14 (P = 0.009)/4 ± 7 mmHg (P = 0.019). Before RDN, eGFR declined by -4.8 ± 3.8 ml/min per 1.73 m per year, and after RDN eGFR improved by +1.5 ± 10 ml/min per 1.73 m at 12 months (P = 0.009).Our observational pilot study in patients with CKD stages 3 and 4 indicates that treatment of hypertension with RDN decreases BP and slows or even halts the decline of renal function.
EVALuna2:3767

Repeating of local therapy of distant metastases increases overall survival in patients with synchronous metastasized rectal cancer-a monocentric analysis - Haderlein, Marlen; Lettmaier, Sebastian; Langheinrich, Melanie; Schmid, Axel; Semrau, Sabine; Hecht, Markus; Beck, Michael; Schmidt, Daniela; Grützmann, Robert; Fietkau, Rainer; Denz, Axel (International Journal of Colorectal Disease, 2018)
PURPOSE: The aim was to evaluate the outcome of treatment-naive patients with synchronous metastatic rectal cancer after chemotherapy with FOLFOXIRI followed by local therapeutic procedures of all tumor lesions as complete as possible. METHODS: We reviewed data of 30 patients with synchronous distant metastatic rectal cancer who underwent chemotherapy with FOLFOXIRI and subsequent local therapy in our institution. RESULTS: Median follow-up was 28 months (range: 8; 74). Cumulative overall survival (OS) and progression-free survival (PFS) was 93.3, 76.9, 55.6% and 46.2, 29.7, 29.7% after 1, 2, 4 years. Non-response to chemotherapy with FOLFOXIRI was associated with a highly significant decreased OS (p < 0.0001). The consistent use of local ablative procedures led to a statistically significant increase in OS (p < 0.0001), but not in PFS (p = 0.635). Patients with ≤ 4 distant metastases showed a better OS (p = 0.033). CONCLUSIONS: Response to intensified first-line chemotherapy with FOLFOXIRI, treatment of the primary rectal tumor, and repeated thorough local ablative procedures in patients with synchronous metastasized rectal cancer may lead to long-term survival, even in a subset of patients with unresectable disease at initial diagnosis.
EVALuna2:36458

Reply to: Longer treatment time and lower radiation doses-an alternative for Graves' ophthalmopathy treatment - Weissmann, Thomas; Putz, Florian; Frey, Benjamin (Strahlentherapie und Onkologie, 2022)
CRIS-Team WoS Importer:2022-05-06

Reporting and Evaluation System for Incidents in the Radiation Therapy to increase Patient Safety, Treatment Quality and the Efficiency of Process Flows - Kornek, Dominik; Lang-Welzenbach, Marga; Beck, A.; Reinhardt, A.; Brandt, Tobias; Bert, Christoph (STRAHLENTHERAPIE UND ONKOLOGIE, 2022)
CRIS-Team WoS Importer:2022-06-03

Required transition from research to clinical application: Report on the 4D treatment planning workshops 2014 and 2015 - Knopf, Antje-Christin; Stuetzer, Kristin; Richter, Christian; Rucinski, Antoni; Da Silva, Joakim; Phillips, Justin; Engelsman, Martijn; Shimizu, Shinichi; Werner, Rene; Jakobi, Annika; Goksel, Orcun; Zhang, Ye; et al. (Physica Medica, 2016)
Since 2009, a 4D treatment planning workshop has taken place annually, gathering researchers working on the treatment of moving targets, mainly with scanned ion beams. Topics discussed during the workshops range from problems of time resolved imaging, the challenges of motion modelling, the implementation of 4D capabilities for treatment planning, up to different aspects related to 4D dosimetry and treatment verification. This report gives an overview on topics discussed at the 4D workshops in 2014 and 2015. It summarizes recent findings, developments and challenges in the field and discusses the relevant literature of the recent years. The report is structured in three parts pointing out developments in the context of understanding moving geometries, of treating moving targets and of 4D quality assurance (QA) and 4D dosimetry. The community represented at the 4D workshops agrees that research in the context of treating moving targets with scanned ion beams faces a crucial phase of clinical translation. In the coming years it will be important to define standards for motion monitoring, to establish 4D treatment planning guidelines and to develop 4D QA tools. These basic requirements for the clinical application of scanned ion beams to moving targets could e.g. be determined by a dedicated ESTRO task group. Besides reviewing recent research results and pointing out urgent needs when treating moving targets with scanned ion beams, the report also gives an outlook on the upcoming 4D workshop organized at the University Medical Center Groningen (UMCG) in the Netherlands at the end of 2016.
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Resection of dominant fusiform gyrus is associated with decline of naming function when temporal lobe epilepsy manifests after the age of five: A voxel-based lesion-symptom mapping study - Reindl, Caroline; Allgäuer, Andrea; Kleiser, Benedict; Onugoren, Müjgan Dogan; Lang, Johannes; Welte, Tamara; Stritzelberger, Jenny; Winder, Klemens; Schwarz, Michael; Gollwitzer, Stephanie; Trollmann, Regina; Rösch, Julie; et al. (NeuroImage: Clinical, 2022)
Objective: To determine patients’ characteristics and regions in the temporal lobe where resections lead to a decline in picture naming. Methods: 311 patients with left hemispheric dominance for language were included who underwent epilepsy surgery at the Epilepsy Center of Erlangen and whose picture naming scores (Boston Naming Test, BNT) were available preoperatively and 6-months postoperatively. Surgical lesions were mapped to an averaged template based on preoperative and postoperative MRI using voxel-based lesion-symptom mapping (VBLSM). Postoperative brain shifts were corrected. The relationship between lesioned brain areas and the presence of a postoperative naming decline was examined voxel-wise while controlling for effects of overall lesion size at first in the total cohort and then restricted to temporal lobe resections. Results: In VBLSM in the total sample, a decline in BNT score was significantly related to left temporal surgery. When only considering patients with left temporal lobe resections (n = 121), 40 (33.1%) significantly worsened in BNT postoperatively. VBLSM including all patients with left temporal resections generated no significant results within the temporal lobe. However, naming decline of patients with epilepsy onset after 5 years of age was significantly associated with resections in the left inferior temporal (extent of BNT decline range: 10.8− 14.4%) and fusiform gyrus (decline range: 12.1−18.4%). Significance: Resections in the posterior part of the dominant fusiform and inferior temporal gyrus was associated with a risk of deterioration in naming performance at six months after surgery in patients with epilepsy onset after 5 years of age but not with earlier epilepsy onset.
CRIS-Team Scopus Importer:2022-08-19
Keywords: Basal temporal language area; Epilepsy surgery; Gyrus fusiformis; Lesion localization; Naming; Neuropsychological outcome

Residual motion mitigation in scanned carbon ion beam therapy of liver tumors using enlarged pencil beam overlap - Richter, Daniel; Graeff, Christian; Jaekel, Oliver; Combs, Stephanie E.; Durante, Marco; Bert, Christoph (Radiotherapy and Oncology, 2014)
Interplay effects may limit the applicability of scanned ion beam therapy for moving tumors even if the motion amplitude is reduced by techniques such as gating or abdominal compression (AC). We investigate the potential of enhanced pencil beam overlap to mitigate residual motion interplay effects in scanned ion beam therapy.Eight patients with hepato cellular carcinoma were selected who were either treated under AC (5 clinical target volumes (CTVs)) or with gating (6 CTVs). We performed 4D dose calculations for treatment plans with variable beam parameters (lateral raster spacing, beam full-width-at-half-maximum (FWHM), iso-energy slice spacing, gating window (GW)) and assessed under- and overdose (V95 and V107), dose homogeneity (HI=D5-D95), and dose volume histograms. The influence of the beam parameters on HI was studied by multivariate regression models.Motion amplitude and FWHM had the largest impact on dose homogeneity, while decreased iso-energy slice spacing and lateral raster spacing had a much smaller or no significant effect, respectively. The multivariate regression models including FWHM, motion amplitude, and IES-spacing explained 86%, 42%, and 71% of the observed variance for AC, 30% and 50% GW, respectively.Residual motion in scanned carbon ion therapy of liver tumors can lead to considerable dose heterogeneities. Using an increased beam spot size dose degradation can be significantly mitigated. Especially for large tumors, increasing the beam spot size is an efficient motion mitigation option readily available at most scanning facilities.
EVALuna2:18311

Respiratory Deformation Estimation in X-Ray-Guided IMRT Using a Bilinear Model - Geimer, Tobias; Ploner, Stefan; Keall, Paul; Bert, Christoph; Maier, Andreas (Informatik aktuell, 2019)
Driving a respiratory motion model in X-ray guided radiotherapy can be challenging in treatments with continuous rotation such as VMAT, as data-driven respiratory signal extraction suffers from angular effects overlapping with respiratory changes in the projection images. Compared to a linear model trained on static acquisition angles, the bilinear model gains flexibility in terms of handling multiple viewpoints at the cost of accuracy. In this paper, we evaluate both models in the context of serving as the surrogate input to a motion model. Evaluation is performed on the 20 patient 4D CTs in a leave-one-phase-out approach yielding a median accuracy drop of only 0.14mm in the 3D error of estimated vector fields of the bilinear model compared to the linear one.
CRIS-Team Scopus Importer:2019-05-14

Response to 6 cycles of chemotherapy with FOLFIRINOX is predictive of overall survival in patients with locally advanced unresectable pancreatic cancer - Haderlein, Marlen; Lubgan, Dorota; Lettmaier, S.; Semrau, S.; Wolf, W.; Golcher, H.; Hohenberger, Werner; Fietkau, Rainer (2016)
EVALuna2:15236

Results of a multicenter 4D computed tomography quality assurance audit: Evaluating image accuracy and consistency - Burghelea, Manuela; Bakkali Tahiri, Jinane; Dhont, Jennifer; Kyndt, Martin; Gulyban, Akos; Szkitsak, Juliane; Bogaert, Evelien; van Gestel, Dirk; Reynaert, Nick (Physics and Imaging in Radiation Oncology, 2023)
Background and purpose: 4D Computed Tomography (4DCT) technology captures the location and movement of tumors and nearby organs at risk over time. In this study, a multi-institutional multi-vendor 4DCT audit was initiated to assess the accuracy of current imaging protocols. Materials and methods: Twelve centers, including thirteen scanners performed a 4DCT acquisition of a dynamic thorax phantom using the institution's own protocol with the in-house breathing monitoring system. Five regular and three irregular breathing patterns were used. Image acquisition and reconstruction were followed by automated image analysis with our in-house developed 4DCT QA program (QAMotion). CT number accuracy, volume deviation, amplitude deviation, and spatial integrity were assessed per pattern using both the segmented volumes and line profiles. Results: Regular breathing curves showed relatively accurate results across all institutions, with mean volume and CT number deviations and median amplitude deviation below 2%, 5 HU and 2 mm, respectively. Results obtained for irregular patterns showed more variation across the institutions. Volume and CT number deviations co-occurred with a blurring of the sphere, interpolation, or double-structure artifacts that were confirmed through the line profiles. For some of the irregular patterns, amplitude deviations up to 6 mm were observed. Maximum Intensity Projection (MaxIP) correctly captured the applied motion amplitude with deviations across all institutions within 2 mm except for double amplitude pattern. Conclusions: All centers invited to participate in the audit responded positively, highlighting the need for a comprehensive yet easy-to-execute 4DCT quality assurance program. The largest variances between the results from one institution to another confirmed that a standardized 4DCT audit is warranted.
CRIS-Team Scopus Importer:2023-09-15

Results of a randomized phase II study comparing pembrolizumab 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) - Gruenwald, V.; Graeven, U.; Ivanyi, P.; Dietz, A.; Hahn, D.; Hackenberg, S.; Kasper, S.; Fietkau, Rainer; Moulin, J-C.; Pink, D.; Schaaf, M.; Klinghammer, K. (ANNALS OF ONCOLOGY, 2021)
CRIS-Team WoS Importer:2021-10-15

Results of brachytherapy trials - Strnad, Vratislav (RADIOTHERAPY AND ONCOLOGY, 2021)
CRIS-Team WoS Importer:2021-06-18

Results of Re-Chemoradiotherapy in Patients with relapsed Glioblastoma WHO IV - Mansoorian, S.; Lettmaier, S.; Goerig, Nicole; Weissmann, T.; Semrau, S.; Fietkau, Rainer; Putz, Florian (STRAHLENTHERAPIE UND ONKOLOGIE, 2019)
CRIS-Team WoS Importer:2019-06-07

Retinal microperfusion after renal denervation in treatment-resistant hypertensive patients - Ott, Christian; Harazny, Joanna M.; Schmid, Axel; Ditting, Tilmann; Veelken, Roland; Bladowski, Marek; Michelson, Georg; Uder, Michael; Schmieder, Roland (Clinical Research in Cardiology, 2015)
High pulsatile pressure and flow in the arteries causes microvascular damage, and hence increased cardio-, and cerebrovascular complications. With advanced stages of hypertensive disease, an exaggerated pulsatile retinal capillary flow (RCF) has been shown, but data about interventional effect are missing.Fifty-one patients with true treatment-resistant hypertension (TRH) underwent renal denervation (RDN) using the Symplicity Flex(TM) catheter and were followed for 12 months. RCF was assessed non-invasively using Scanning laser Doppler flowmetry (SLDF) before, 6 (6 M), and 12 (12 M) months after RDN. RCF was measured in systole and diastole and pulsed RCF (difference of RCF in systole minus diastole) was calculated. In addition, flicker light-induced vasodilation (representing vasodilatory capacity) was assessed.Systolic and diastolic office blood pressure (BP) as well as 24-h ABPM decreased significantly 6 M and 12 M after RDN, compared to baseline values (all p < 0.001). There was a significant reduction of pulsed RCF 6 M (231 ± 81 versus 208 ± 68 AU, p = 0.046) and 12 M (194 ± 72 AU, p = 0.001) after RDN, whereas the mean RCF was unchanged. Moreover, there was a significant increase of flicker light-induced vasodilation after RDN (p = 0.043).In hypertensive patients with TRH, we observed a decrease of pulsed RCF 6 M and 12 M after RDN and an increase of vasodilatory capacity, in parallel to decreases in BP and heart rate. The reduction of pulsed RCF after RDN implies a decrease of shear stress on the vascular wall by the pulsed blood flow. This and the increment of vasodilatory capacity suggest an improvement of retinal (and potentially cerebral) microcirculation.
EVALuna2:3762

Retrospective fusion of F-18-FDG-PET and CT: additional diagnostic information in melanoma patients - Römer, Wolfgang; Nömayr, Anton; Greess, Holger; Fiedler, Ekkehard; Platsch, Günter; Pfahlberg, Annette; Hothorn, Torsten; Hornegger, Joachim; Bautz, Werner; Kuwert, Torsten (Eur J Nucl Med Mol Imaging, 2004)

Retrospective fusion of F-18-FDG-PET and CT: additional diagnostic information in melanoma patients. - Römer, Wolfgang; Nömayr, Anton; Greess, Holger; Fiedler, Ekkehard; Platsch, Günter; Pfahlberg, Annette; Hothorn, Torsten; Hornegger, Joachim; Bautz, Werner; Kuwert, Torsten (Philadelphia J Nucl Med, 2004)

Retrospective interactive rigid fusion of 18F-FDG-PET and CT: Additional diagnostic information in melanoma patients - Römer, Wolfgang; Nömayr, Anton; Greess, Holger; Fiedler, Ekkehard; Platsch, Günter; Schuler-Thurner, Beatrice; Pfahlberg, Annette; Hothorn, Torsten; Schuler, Gerold; Hornegger, Joachim; Bautz, Werner; Kuwert, Torsten (Nuklearmedizin-Nuclear Medicine, 2006)
Aim: This study investigates whether interactive rigid fusion of routine PET and CT data improves localization, detection and characterization of lesions compared to separate reading. For this purpose, routine PET and CT scans of patients with metastases from malignant melanoma were used. Patients, methods: In 34 patients with histologically confirmed malignant melanoma, FDG-PET and spiral CT were performed using clinical standard protocols. For all of these patients, gold standard was available. Clinical and radiological follow-up identified 82 lesions as definitely pathological. Two board-certified nuclear medicine physicians and two board-certified radiologists analyzed PET and CT images independently from each other. For each patient up to 32 anatomical regions (24 lymph node regions, 8 extranodular regions) were systematically classified. Discordant areas were interactively analyzed in manually and rigidly registered images using a commercially available fusion tool. No side-by-side reading was performed. Results: Image fusion disclosed that the evaluation of the PET images alone led to a mislocalization in 26 of 91 focally FDG enhancing lesions. The overall sensitivities of PET, CT, and image fusion were 85, 88, and 94%, respectively; the overall specificities of PET, CT and image fusion were 98, 95 and 100%, respectively. Image fusion exhibited statistically significant higher specificity values as compared with CT. Ten definitely malignant sites were false-negative in CT, but could be detected by PET. On the other hand, twelve metastases were false-negative in PET, but could be detected by CT. These included two lesions, which had a clear correlate on the PET image when the fused images were evaluated. On the whole, registration of the PET and CT images yielded additional diagnostic information in 44% of the definitely malignant lesions. Conclusion: Retrospective image fusion of independently obtained PET and CT data is particularly valuable in exactly lodizing foci of abnormal FDG uptake and improves the detection of metastases of malignant melanoma. © 2006 Schattauer GmbH.

Reviewer and Publication Behavior in Radiation Therapy/Radiation Biology / Medical Physics in Germany, Austria and Switzerland - an Online Survey by jDEGRO - Kaesmann, L.; Baasse, A.; Frey, Benjamin; Fleischmann, D.; Gauer, T.; Ebert, N.; Hecht, Markus; Krug, D.; Niyazi, M.; Maeurer, M. (STRAHLENTHERAPIE UND ONKOLOGIE, 2020)
CRIS-Team WoS Importer:2020-10-02

Risk-adapted modulation through deintensification of cancer treatments: an ESMO classification - Hannoun-Levi, J. M.; Gutierrez, C.; Polgar, C.; Strnad, Vratislav (Annals of Oncology, 2022)
CRIS-Team Scopus Importer:2022-10-21

Risk analysis for radiotherapy at the Universitätsklinikum Erlangen - Lohmann, Daniel; Lang-Welzenbach, Marga; Feldberger, Lorenz; Sommer, Ellen; Bücken, Stefan; Lotter, Michael; Ott, Oliver; Fietkau, Rainer; Bert, Christoph (Zeitschrift für Medizinische Physik, 2022)
Purpose: Risk analysis is required by various laws and regulations in Germany and has an impact on each department of a large clinic. We provide an overview of the relevant laws and regulations in Germany and present the technical and organizational experience of introducing risk analysis in the Department of Radiation Oncology at the Universitätsklinikum Erlangen. Methods: Risk analysis was performed with an in-house developed extension of our intranet platform and ticketing system. Risks were classified according to occurrence and severity, each on a 5-level scale resulting into a risk matrix. An interdisciplinary team of six experienced members formed the core meeting weekly. Results: A total of 38 risks and 50 measures have been identified in 41 1 h-meetings corresponding to approx. 260 working hours. Risk was distributed 8/20/13 to the categories critical (n = 8), monitoring (n = 20), and conditionally acceptable (n = 13). Risk analysis has been evaluated before and after introducing measures. Conclusion: The risk analysis method introduced has been successfully used in routine operations for over a year. Risk analysis takes time and effort. However, because experts from different disciplines meet each other every week, the overall workflow of the radiation oncology department can be improved efficiently and continuously.
CRIS-Team Scopus Importer:2022-04-01
Keywords: GBA; Radiation therapy; Risk analysis; Strahlenschutzverordnung

Risk of cancer incidence before the age of 15 years after exposure to ionising radiation from computed tomography: results from a German cohort study - Krille, L.; Dreger, S.; Schindel, R.; Albrecht, T.; Asmussen, M.; Barkhausen, Joerg; Berthold, J. D.; Chavan, A.; Claussen, C.; Forsting, M.; Gianicolo, E. A. L.; Jablonka, K.; et al. (Radiation and Environmental Biophysics, 2015)
The aim of this cohort study was to assess the risk of developing cancer, specifically leukaemia, tumours of the central nervous system and lymphoma, before the age of 15 years in children previously exposed to computed tomography (CT) in Germany. Data for children with at least one CT between 1980 and 2010 were abstracted from 20 hospitals. Cancer cases occurring between 1980 and 2010 were identified by stochastic linkage with the German Childhood Cancer Registry (GCCR). For all cases and a sample of non-cases, radiology reports were reviewed to assess the underlying medical conditions at time of the CT. Cases were only included if diagnosis occurred at least 2 years after the first CT and no signs of cancer were recorded in the radiology reports. Standardised incidence ratios (SIR) using incidence rates from the general population were estimated. The cohort included information on 71,073 CT examinations in 44,584 children contributing 161,407 person-years at risk with 46 cases initially identified through linkage with the GCCR. Seven cases had to be excluded due to signs possibly suggestive of cancer at the time of first CT. Overall, more cancer cases were observed (O) than expected (E), but this was mainly driven by unexpected and possibly biased results for lymphomas. For leukaemia, the SIR (SIR = O/E) was 1.72 (95 % CI 0.89-3.01, O = 12), and for CNS tumours, the SIR was 1.35 (95 % CI 0.54-2.78, O = 7). Despite careful examination of the medical information, confounding by indication or reverse causation cannot be ruled out completely and may explain parts of the excess. Furthermore, the CT exposure may have been underestimated as only data from the participating clinics were available. This should be taken into account when interpreting risk estimates.
EVALuna2:14517

ROI optimisation for surface guided radiation therapy - Sauer, Tim-Oliver; Popp, D.; Fietkau, Rainer; Bert, Christoph (RADIOTHERAPY AND ONCOLOGY, 2020)
CRIS-Team WoS Importer:2021-06-18

Role of Brachytherapy in the Postoperative Management of Endometrial Cancer: Decision-Making Analysis among Experienced European Radiation Oncologists - Glatzer, Markus; Tanderup, Kari; Rovirosa, Angeles; Fokdal, Lars; Ordeanu, Claudia; Tagliaferri, Luca; Chargari, Cyrus; Strnad, Vratislav; Dimopoulos, Johannes Athanasios; Šegedin, Barbara; Cooper, Rachel; Nakken, Esten Søndrol; et al. (Cancers, 2022)
Background: There are various society-specific guidelines addressing adjuvant brachytherapy (BT) after surgery for endometrial cancer (EC). However, these recommendations are not uniform. Against this background, clinicians need to make decisions despite gaps between best scientific evidence and clinical practice. We explored factors influencing decision-making for adjuvant BT in clinical routine among experienced European radiation oncologists in the field of gynaecological radiotherapy (RT). We also investigated the dose and technique of BT. Methods: Nineteen European experts for gynaecological BT selected by the Groupe Européen de Curiethérapie and the European Society for Radiotherapy & Oncology provided their decision criteria and technique for postoperative RT in EC. The decision criteria were captured and converted into decision trees, and consensus and dissent were evaluated based on the objective consensus methodology. Results: The decision criteria used by the experts were tumour extension, grading, nodal status, lymphovascular invasion, and cervical stroma/vaginal invasion (yes/no). No expert recommended adjuvant BT for pT1a G1-2 EC without substantial LVSI. Eighty-four percent of experts recommended BT for pT1a G3 EC without substantial LVSI. Up to 74% of experts used adjuvant BT for pT1b LVSI-negative and pT2 G1–2 LVSI-negative disease. For 74–84% of experts, EBRT + BT was the treatment of choice for nodal-positive pT2 disease and for pT3 EC with cervical/vaginal invasion. For all other tumour stages, there was no clear consensus for adjuvant treatment. Four experts already used molecular markers for decision-making. Sixty-five percent of experts recommended fractionation regimens of 3 × 7 Gy or 4 × 5 Gy for BT as monotherapy and 2 × 5 Gy for combination with EBRT. The most commonly used applicator for BT was a vaginal cylinder; 82% recommended image-guided BT. Conclusion: There was a clear trend towards adjuvant BT for stage IA G3, stage IB, and stage II G1–2 LVSI-negative EC. Likewise, there was a non-uniform pattern for BT dose prescription but a clear trend towards 3D image-based BT. Finally, molecular characteristics were already used in daily decision-making by some experts under the pretext that upcoming trials will bring more clarity to this topic.
CRIS-Team Scopus Importer:2022-02-25
Keywords: Brachytherapy; Decision tree; Decision-making; Endometrial cancer

Role of tumor cell senescence in non-professional phagocytosis and cell-in-cell structure formation - Gottwald, Dorian; Putz, Florian; Hohmann, Nora; Büttner-Herold, Maike; Hecht, Markus; Fietkau, Rainer; Distel, Luitpold (BMC Molecular and Cell Biology, 2020)
Background: Non-professional phagocytosis is usually triggered by stimuli such as necrotic cell death. In tumor therapy, the tumors often disappear slowly and only long time after the end of therapy. Here, tumor therapy inactivates the cells by inducing senescence. Therefore, study focused whether senescence is a stimulus for non-professional phagocytosis or whether senescent cells themselves phagocytize non-professionally. Results: Senescence was induced in cell lines by camptothecin and a phagocytosis assay was performed. In tissue of a cohort of 192 rectal cancer patients senescence and non-professional phagocytosis was studied by anti-histone H3K9me3 and anti-E-cadherin staining. Senescent fibroblasts and pancreas carcinoma cells phagocytize necrotic cells but are not phagocytized. In the tissue of rectal carcinoma, senescent cells can phagocytize and can be phagocytized. A high number of senescent cells and, at the same time, high numbers of non-professional phagocytizing cells in the rectal carcinoma tissue lead to an extremely unfavorable prognosis regarding overall survival. Conclusion: Senescent cells can be non-professionally phagocytized and at the same time they can non-professionally phagocytize in vivo. In vitro experiments indicate that it is unlikely that senescence is a strong trigger for non-professional phagocytosis. Combined high rates of non-professional phagocytosis and high rates of senescence are an extremely poor prognostic factor for overall survival.
CRIS-Team Scopus Importer:2020-11-13
Keywords: Camptothecin; Cannibalism; Cell-in-cell; Entosis; Non-professional phagocytosis; Prognostic factor and survival; Rectal cancer; Senescence

Rolle der Radiotherapie beim Pankreaskarzinom - Goerig, Nicole; Fietkau, Rainer (Onkologe, 2019)
Background: Pancreatic cancer is a tumor with a worldwide incidence of approximately 340,000 newly diagnosed patients per year. With a 5-year overall survival of 2–6% the prognosis is very poor. At the time of diagnosis, resection is the only curative option primarily possible for approximately 30% of the patients. Chemoradiotherapy is a treatment option for achieving resectability of primarily unresectable tumors, improving the results of surgery and also for increasing survival of definitively inoperable patients with advanced states of the disease. Objective: This article gives a current overview on the role of radiotherapy for treatment of pancreatic cancer. Material and methods: Literature analysis of fundamental studies, original and review articles and of current trials. Results: Data from prospective and retrospective analyses show that neoadjuvant chemoradiotherapy of pancreatic cancer increases the number of resectable patients and improves the overall survival. There are comparable data for adjuvant chemoradiotherapy of resected patients with additional risk factors (R1, N +). In cases where resection is definitively impossible, chemoradiotherapy also contributes to local tumor control and improving therapy-free intervals, potentially even to the prognosis. In the palliative setting, irradiation can be used for local pain management. Discussion: The role of radiotherapy as part of multimodal treatment concepts for pancreatic cancer is currently under discussion; however, there are a number of retrospective and prospective studies clearly suggesting the benefits of radiotherapy in addition to surgery and chemotherapy. Prospective studies are necessary for further verification using modern techniques for radiotherapy, such as stereotactic and intensity-modulated radiotherapy. The use of older studies, with inadequate irradiation techniques and obsolete doses from today’s point of view, for evaluating the effects of radiotherapy is not acceptable.
CRIS-Team Scopus Importer:2019-08-02
Keywords: Adjuvant; Chemoradiotherapy; Inoperability; Neoadjuvant; Relapse therapy

Romancing the Boost - the Higher, the Better? - Sedlmayer, Felix; Sautter-Bihl, Marie-Luise; Sauer, Rolf (Breast Care, 2015)
EVALuna2:18278

Rsk2 controls synovial fibroblast hyperplasia and the course of arthritis - Derer, Anja; Boehm, Christina; Groetsch, Bettina; Gruen, Joachim R.; Gruetzkau, Andreas; Stock, Michael; Böhm, Sybille; Sehnert, Bettina; Gaipl, Udo; Schett, Georg; Hueber, Axel; David, Jean-Pierre (Annals of the Rheumatic Diseases, 2016)
Arthritis is a chronic inflammatory disease characterised by immune cell infiltration and mesenchymal cell expansion in the joints. Although the role of immune cells in arthritis is well characterised, the development of mesenchymal cell hyperplasia needs to be better defined. Here, we analysed the role of the ribosomal S6 kinase Rsk2, which we found to be highly activated in joints of patients with arthritis, in the development of mesenchymal cell hyperplasia.We genetically inactivated Rsk2 in the tumour necrosis factor (TNF)-? transgenic (TNFtg) mice, an animal model for human inflammatory arthritis. Clinical and histological signs of arthritis as well as molecular markers of inflammation and joint destruction were quantified. Fibroblast-like synoviocytes (FLS) were characterised in vitro and the effect of Rsk2 deletion on the pattern of gene expression was determined.Rsk2 deficiency in TNFtg mice results in earlier and exacerbated inflammation as well as increased bone and cartilage destruction. The production of inflammatory cytokines, matrix metalloproteinases and osteoclastogenic molecules was significantly increased in vivo upon Rsk2 inactivation. Bone marrow deficient in Rsk2 could not transfer this phenotype, indicating that Rsk2 expression in mesenchymal cells controls the course of arthritis. Indeed, Rsk2 deficiency was associated with a more activated phenotype and higher proliferative capacity of FLS, thereby increasing cytokines and production of matrix proteinases.Rsk2 emerges as a key regulator of mesenchymal cell numbers in the joint and thereby could be targeted to control the inflammatory and tissue-destructive feature of joints in arthritis.
EVALuna2:13016

Safety and efficacy of single cycle induction treatment with cisplatin/docetaxel/ durvalumab/tremelimumab in locally advanced HNSCC: first results of CheckRad-CD8 - Hecht, Markus; Gostian, Antoniu Oreste; Eckstein, Markus; Rutzner, Sandra; Von Der Grün, Jens; Illmer, Thomas; Hautmann, Matthias G.; Klautke, Gunther; Laban, Simon; Brunner, Thomas; Hinke, Axel; Becker, Ina; et al. (Journal for ImmunoTherapy of Cancer, 2020)
BACKGROUND: To determine safety and efficacy of single cycle induction treatment with cisplatin/docetaxel and durvalumab/tremelimumab in stage III-IVB head and neck cancer. METHODS: Patients received a single cycle of cisplatin 30 mg/m² on days 1-3 and docetaxel 75 mg/m² on day 1 combined with durvalumab 1500 mg fix dose on day 5 and tremelimumab 75 mg fix dose on day 5. Patients with pathologic complete response (pCR) in the rebiopsy after induction treatment or at least 20% increase of intratumoral CD8+ cell density in the rebiopsy compared with baseline entered radioimmunotherapy with concomitant durvalumab/tremelimumab. The objective of this interim analysis was to analyze safety and efficacy of the chemoimmunotherapy-induction treatment before radioimmunotherapy. RESULTS: A total of 57 patients were enrolled, 56 were treated. Median pretreatment intratumoral CD8+ cell density was 342 cells/mm². After induction treatment, 27 patients (48%) had a pCR in the rebiopsy and further 25 patients (45%) had a relevant increase of intratumoral CD8+ cells (median increase by a factor of 3.0). Adverse event (AE) grade 3-4 appeared in 38 patients (68%) and mainly consisted of leukopenia (43%) and infections (29%). Six patients (11%) developed grade 3-4 immune-related AE. Univariate analysis computed p16 positivity, programmed death ligand 1 immune cell area and intratumoral CD8+ cell density as predictors of pCR. On multivariable analysis, intratumoral CD8+ cell density predicted pCR independently (OR 1.0012 per cell/mm², 95% CI 1.0001 to 1.0022, p=0.016). In peripheral blood CD8+ cells, the coexpression of programmed death protein 1 significantly increased especially in patients with pCR. CONCLUSIONS: Single cycle induction treatment with cisplatin/docetaxel and durvalumab/tremelimumab is feasible and achieves a high biopsy-proven pCR rate.
CRIS-Team Scopus Importer:2020-10-23
Keywords: CD8-Positive T-lymphocytes; clinical trials; combined modality therapy; head and neck neoplasms; Phase II as topic; radioimmunotherapy

Salivary gland carcinoma (SGC) with perineural spread and/or positive resection margin - High locoregional control rates after photon (chemo) radiotherapy - Experience from a monocentric analysis - Haderlein, Marlen; Scherl, Claudia; Semrau, Sabine; Lettmaier, Sebastian; Hecht, Markus; Putz, Florian; Iro, Heinrich; Agaimy, Abbas; Fietkau, Rainer (Radiation Oncology, 2019)
Background: The aim was to evaluate the outcome, especially locoregional control of patients with locally advanced salivary gland carcinoma (SGC) with perineural spread (Pn1) and/or positive resection margins (R1/2) after postoperative photon (chemo) radiotherapy in a single centre. Methods: We retrospectively reviewed data of 65 patients with newly diagnosed locally advanced SGC without distant metastases who underwent radio (chemo) therapy in the department of radiation oncology of the university hospital of Erlangen from January 2000 until April 2017. Kaplan Meier method was used to calculate survival and recurrence rates. In univariate analysis the log-rank test was used to correlate patient-/tumor- and treatment-related parameters to survival and recurrence rates. Results: Median follow-up was 45 months (range: 6; 215). After 1, 3, 5 years cumulative incidence of local and locoregional failure was 3.1, 7.0, 7.0% and 3.1, 9.7, 12.9%, whereas cumulative incidence of distant metastases (DM) was 15.6, 36.0, 44.0%. After 1,3, 5 years cumulative Overall (OS) and Disease-free survival (DFS) was 90.5, 74.9, 63.9% and 83.0, 54.8, 49.4%. The only significant predictor for decreased local and locoregional control was a macroscopic resection margin(R2) (p = 0.002 and p = 0.04). High-grade histology (p = 0.006), lymph node metastases with extracapsular spread (p = 0.044) and an advanced T-stage (p = 0.031) were associated with an increased rate of DM. High-grade histology was the only factor predicting for a decreased DFS (p = 0.014). Conclusion: Photon radiotherapy leads to high local and locoregional control rates in a high-risk patient population with SGC with microscopically positive resection margins and/or perineural spread. The most common site of disease recurrence was distant metastases. Therefore the real challenge for the future should be to prevent distant metastases.
CRIS-Team Scopus Importer:2019-05-03
Keywords: Locoregional control; Perineural spread; Photon radiotherapy; Positive resection margin; Salivary gland cancer

Salvage external beam radiation therapy of biochemical relapse after radical prostatectomy: Results and potential role of PET/CT - Rutzner, Sandra; Lubgan, Dorota; Wullich, Bernd; Kuehn, R.; Kuwert, Torsten; Fietkau, Rainer (2018)
EVALuna2:35905

Salvage HDR/PDR brachytherapy combined with interstitial hyperthermia in locally recurrent prostate adenocarcinoma after previous irradiation - actual status of multicenter phase II study - Kukielka, A.; Strnad, Vratislav; Dabkowski, M. (2018)
EVALuna2:36541

Salvage laryngectomy after primary radio- and radiochemotherapy : A retrospective study - Sievert, Matti; Goncalves, Miguel; Binder, Benedicta; Mueller, Sarina K.; Rupp, Robin; Koch, Michael; Dürr, Stephan; Traxdorf, Maximilian; Hecht, Markus; Iro, Heinrich; Gostian, Antoniu-Oreste (HNO, 2021)
BACKGROUND: Recurrent and residual laryngeal cancer after organ-preserving radio- or radiochemotherapy is associated with a poor prognosis. Salvage surgery is the most important therapeutic option in these cases. OBJECTIVE: The study assessed rates of recurrence and residual tumor as well as survival and complication rates after salvage laryngectomy at the authors' academic cancer center. MATERIALS AND METHODS: A retrospective examination of all patients receiving laryngectomy between 2001 and 2019 due to tumor residuals or recurrence after primary radio- and radiochemotherapy was conducted. RESULTS: A total of 33 salvage procedures were performed. Defect reconstruction was performed by free flap surgery in 30.3% (n = 10) and regional flap surgery in 15.2% (n = 5) . One patient received regional flap surgery and free flap surgery simultaneously. Overall survival after 1, 2, and 5 years was 68.7, 47.9, and 24.2%, and disease-free survival was 81.6, 47.8, and 24.2%, respectively, with 48.5% (n = 16) postoperative tumor recurrences overall. Disease-free survival was significantly shorter for tumor extension into or onto the hypopharynx (p = 0.041). Postoperatively, 72.7% of patients developed a pharyngocutaneous fistula, of which 24.2% required surgical treatment. The hospital stay was 28.0 ± 16.1 days. CONCLUSION: Salvage laryngectomy is associated with a high rate of treatable complications and high morbidity. Nevertheless, considering the advanced tumor stages treated, it allows for respectable oncological results.
CRIS-Team Scopus Importer:2021-10-01
Keywords: Laryngeal neoplasms; Postoperative complications; Recurrence; Salvage therapy; Treatment outcome

Salvage-Laryngektomie nach primärer Radio- und Radiochemotherapie: Eine retrospektive Fallzusammenfassung - Sievert, Matti; Goncalves, Miguel; Binder, Benedicta; Mueller, Sarina K.; Rupp, Robin; Koch, Michael; Dürr, Stephan; Traxdorf, Maximilian; Hecht, Markus; Iro, Heinrich; Gostian, Antoniu-Oreste (HNO, 2021)
Background: Recurrent and residual laryngeal cancer after organ-preserving radio- or radiochemotherapy is associated with a poor prognosis. Salvage surgery is the most important therapeutic option in these cases. Objective: The study assessed rates of recurrence and residual tumor as well as survival and complication rates after salvage laryngectomy at the authors’ academic cancer center. Materials and methods: A retrospective examination of all patients receiving laryngectomy between 2001 and 2019 due to tumor residuals or recurrence after primary radio- and radiochemotherapy was conducted. Results: A total of 33 salvage procedures were performed. Defect reconstruction was performed by free flap surgery in 30.3% (n = 10) and regional flap surgery in 15.2% (n = 5). One patient received regional flap surgery and free flap surgery simultaneously. Overall survival after 1, 2, and 5 years was 68.7, 47.9, and 24.2%, and disease-free survival was 81.6, 47.8, and 24.2%, respectively, with 48.5% (n = 16) postoperative tumor recurrences overall. Disease-free survival was significantly shorter for tumor extension into or onto the hypopharynx (p = 0.041). Postoperatively, 72.7% of patients developed a pharyngocutaneous fistula, of which 24.2% required surgical treatment. The hospital stay was 28.0 ± 16.1 days. Conclusion: Salvage laryngectomy is associated with a high rate of treatable complications and high morbidity. Nevertheless, considering the advanced tumor stages treated, it allows for respectable oncological results.
CRIS-Team Scopus Importer:2021-04-23
Keywords: Laryngeal neoplasms; Postoperative complications; Recurrence; Salvage therapy; Treatment outcome

Salvage-radiation therapy and regional hyperthermia for biochemically recurrent prostate cancer after radical prostatectomy (Results of the planned interim analysis) - Beck, Marcus; Ghadjar, Pirus; Mehrhof, Felix; Zips, Daniel; Paulsen, Frank; Wegener, Daniel; Burock, Susen; Kaul, David; Stromberger, Carmen; Nadobny, Jacek; Ott, Oliver; Fietkau, Rainer; et al. (Cancers, 2021)
Efforts to improve the outcome of prostate cancer (PC) patients after radical prostatectomy (RP) include adjuvant or salvage radiation therapy (SRT), but still up to 50% of patients develop a disease progression after radiotherapy (RT). Regional hyperthermia (HT) is well-known to improve tumor sensitivity to RT in several entities. Here we report on a planned interim analysis of tolera-bility and feasibility after recruitment of the first 50 patients of a trial combining SRT and HT. We conducted a prospective multicenter non-randomized Phase-II-Trial (HTProstate-NCT04159051) in-vestigating the implementation of combined moderate-dose escalated SRT (70 Gy in 35 fractions) and locoregional deep HT (7–10 HT sessions). The primary endpoints were the rate of acute genito-urinary (GU), gastrointestinal (GI), and HT-related toxicities, completed HT sessions (≥7), and SRT applications per protocol (≥95% of patients). The two-step design included a planned interim analysis for acute GU-, GI-and HT-specific toxicities to ensure patients’ safety. Between November 2016 and December 2019, 52 patients entered into the trial. After 50 patients completed therapy and three months of follow-up, we performed the planned interim analysis. 10% of patients developed acute grade 2 GU and 4% grade 2 GI toxicities. No grade ≥3 GU or GI toxicities occurred. HT-specific symptoms grade 2 and 3 were observed in 4% and 2% of all patients. Thus, the pre-specified criteria for safety and continuation of recruitment were met. Moreover, ≥7 HT treatments were applicable, indicating the combination of SRT + HT to be feasible. Evaluation of early QoL showed no significant changes. With its observed low rate of GU and GI toxicities, moderate and manageable rates of HT-specific symptoms, and good feasibility, the combined SRT + HT seems to be a promising treatment approach for biochemical recurrence after RP in PC patients.
CRIS-Team Scopus Importer:2021-03-19
Keywords: Dose-escalation; Hyperthermia; Postoperative; Prostate cancer; Radiosensitiza-tion; Salvage radiation therapy

SAR Measurements of Coaxial Antennas in a Muscle Equivalent Water Phantom - Erb, J.; Engelbrecht, Rainer; Schaller, Gerhard; Seegenschmiedt, Heinrich; Fietkau, Rainer; Sauer, R.; Ross, D. (Hyperthermia in Clinical Oncology - In Memory of Dr. Mildred Scheel, 1993)
UnivIS-Import:2015-04-16:Pub.1993.tech.IE.LEH.sarmea_0

SAR Measurements of Coaxial Antennas Used for Interstitial/Endocavitary HT. - Erb, J.; Engelbrecht, Rainer; Schaller, Gerhard; Ross, D.; Seegenschmiedt, Heinrich; Fietkau, Rainer; Sauer, R. (13^th Meeting of the Europ. Soc. Hyperthermia Oncology ESHO, 1993)
UnivIS-Import:2015-04-16:Pub.1993.tech.IE.LEH.sarmea

SARS-CoV-2-seronegative subjects target CTL epitopes in the SARS-CoV-2 nucleoprotein cross-reactive to common cold coronaviruses - Schmidt, Kristin; Nganou-Makamdop, K.; Tenbusch, Matthias; El Kenz, B.; Maier, Clara; Lapuente, Dennis; Überla, Klaus; Spriewald, Bernd; Bergmann, Sabrina; Harrer, Ellen; Harrer, Thomas (JOURNAL OF THE INTERNATIONAL AIDS SOCIETY, 2021)
CRIS-Team WoS Importer:2021-11-26

Scanned ion beam therapy for prostate carcinoma: Comparison of single plan treatment and daily plan-adapted treatment - Hild, Sebastian; Graeff, Christian; Rucinski, Antoni; Zink, Klemens; Habl, Gregor; Durante, Marco; Herfarth, Klaus; Bert, Christoph (Strahlentherapie und Onkologie, 2016)
Intensity-modulated particle therapy (IMPT) for tumors showing interfraction motion is a topic of current research. The purpose of this work is to compare three treatment strategies for IMPT to determine potential advantages and disadvantages of ion prostate cancer therapy.Simulations for three treatment strategies, conventional one-plan radiotherapy (ConvRT), image-guided radiotherapy (IGRT), and online adaptive radiotherapy (ART) were performed employing a dataset of 10 prostate cancer patients with six CT scans taken at one week intervals. The simulation results, using a geometric margin concept (7-2 mm) as well as patient-specific internal target volume definitions for IMPT were analyzed by target coverage and exposure of critical structures on single fraction dose distributions.All strategies led to clinically acceptable target coverage in patients exhibiting small prostate motion (mean displacement <4 mm), but IGRT and especially ART led to significant sparing of the rectum. In 20% of the patients, prostate motion exceeded 4 mm causing insufficient target coverage for ConvRT (V95mean = 0.86, range 0.63-0.99) and IGRT (V95mean = 0.91, range 0.68-1.00), while ART maintained acceptable target coverage.IMPT of prostate cancer demands consideration of rectal sparing and adaptive treatment replanning for patients exhibiting large prostate motion.
EVALuna2:18350

Scleroderma and Radiation Sensitivity - Schenker, Hannah; Schuster, Barbara; Fietkau, Rainer; Distel, Luitpold (STRAHLENTHERAPIE UND ONKOLOGIE, 2019)
CRIS-Team WoS Importer:2019-06-07

“sCT-Feasibility” - a feasibility study for deep learning-based MRI-only brain radiotherapy - Grigo, Johanna; Szkitsak, Juliane; Höfler, Daniel; Fietkau, Rainer; Putz, Florian; Bert, Christoph (Radiation Oncology, 2024)
Background: Radiotherapy (RT) is an important treatment modality for patients with brain malignancies. Traditionally, computed tomography (CT) images are used for RT treatment planning whereas magnetic resonance imaging (MRI) images are used for tumor delineation. Therefore, MRI and CT need to be registered, which is an error prone process. The purpose of this clinical study is to investigate the clinical feasibility of a deep learning-based MRI-only workflow for brain radiotherapy, that eliminates the registration uncertainty through calculation of a synthetic CT (sCT) from MRI data. Methods: A total of 54 patients with an indication for radiation treatment of the brain and stereotactic mask immobilization will be recruited. All study patients will receive standard therapy and imaging including both CT and MRI. All patients will receive dedicated RT-MRI scans in treatment position. An sCT will be reconstructed from an acquired MRI DIXON-sequence using a commercially available deep learning solution on which subsequent radiotherapy planning will be performed. Through multiple quality assurance (QA) measures and reviews during the course of the study, the feasibility of an MRI-only workflow and comparative parameters between sCT and standard CT workflow will be investigated holistically. These QA measures include feasibility and quality of image guidance (IGRT) at the linear accelerator using sCT derived digitally reconstructed radiographs in addition to potential dosimetric deviations between the CT and sCT plan. The aim of this clinical study is to establish a brain MRI-only workflow as well as to identify risks and QA mechanisms to ensure a safe integration of deep learning-based sCT into radiotherapy planning and delivery. Discussion: Compared to CT, MRI offers a superior soft tissue contrast without additional radiation dose to the patients. However, up to now, even though the dosimetrical equivalence of CT and sCT has been shown in several retrospective studies, MRI-only workflows have still not been widely adopted. The present study aims to determine feasibility and safety of deep learning-based MRI-only radiotherapy in a holistic manner incorporating the whole radiotherapy workflow. Trial registration: NCT06106997.
CRIS-Team Scopus Importer:2024-03-22
Keywords: Artificial intelligence; Deep learning; MRI; MRI-only workflow; MRonly; Radiotherapy; sCT; Stereotactic radiotherapy; Synthetic CT

Secondary Tracheoesophageal Puncture After Laryngectomy Increases Complications With Shunt and Voice Prosthesis - Scherl, Claudia; Kauffels, Julia; Schützenberger, Anne; Döllinger, Michael; Bohr, Christopher; Dürr, Stephan; Fietkau, Rainer; Haderlein, Marlen; Koch, Michael; Traxdorf, Maximilian; Mantsopoulos, Konstantinos; Mueller, Sarina K.; et al. (Laryngoscope, 2020)
Objectives/Hypothesis To evaluate the demographics, clinical features, management, and prognostic indicators of tracheoesophageal puncture complications in patients undergoing placement of voice prosthesis following cancer treatment.
CRIS-Team WoS Importer:2020-02-21

Second Conservative Treatment for Local Recurrence Breast Cancer: A GEC-ESTRO Oncological Outcome and Prognostic Factor Analysis - Hannoun-Levi, Jean Michel; Gal, Jocelyn; Polgar, Csaba; Strnad, Vratislav; Loessl, Kristina; Polat, Bulent; Kauer-Domer, Daniela; Schiappa, Renaud; Gutierrez, Crisitna (International Journal of Radiation Oncology Biology Physics, 2023)
Purpose: For second ipsilateral breast tumor event (2nd IBTE), second conservative treatment (2nd CT) combining lumpectomy plus accelerated partial breast reirradiation (APBrI) represents a curative option. The aim of this study was to analyze oncological prognostic factors for patients with a 2nd IBTE treated with 2nd CT. Methods and Materials: An analysis of clinical practices was conducted across 7 academic hospitals/cancer centers in 6 European countries based on the GEC-ESTRO database. Patients presenting a 2nd IBTE occurring after conservative surgery (lumpectomy + axillary evaluation) and irradiation performed for the primary tumor underwent a 2nd CT with brachytherapy-based APBrI. The main outcome was 5-year cumulative incidence (CI) rate of second local relapse. All analyzed patients were classified according to risk groups for Groupe Européen de Curiethérapie–European Society for Therapeutic Radiology and Oncology (GEC-ESTRO) accelerated partial breast irradiation (APBI) and molecular classification and time interval between first and second breast surgery (TIS1S2). Finally, we combined GEC-ESTRO APBI, molecular, and TIS1S2 risk groups, leading to the definition of a new score (named TAM: score based on the combination of time interval [T] between first and second surgery and APBI [A] and molecular [M] classifications) specifically designed for 2nd IBTE oncological outcome analysis. Results: From July 1994 to January 2021, a total of 508 patients received a 2nd CT. At the time of 2nd IBTE, median age was 64.6 years (range, 56.2-72.6). With a median follow-up of 60.9 months (56.2-72.6), the 5-year second local relapse CI rate was 4% (95% confidence interval [95% CI], 2%-6%). The 5-year distant metastasis disease CI rate was 7% (95% CI, 4%-10%). Five-year disease-free and overall survival rates were 89% (95% CI, 86%-93%) and 91% (95% CI, 88%-94%), respectively. In multivariate analysis, TAM score was an independent prognostic factor for all the oncological items (P <.001) except disease-specific survival (P =.07) and overall survival (P =.09). The grade ≥3 late toxicity rate was 12.1%. Conclusions: This analysis of 2nd CT combining lumpectomy with APBrI for 2nd IBTE confirmed the excellent oncological results obtained after 2nd CT. Furthermore, the GEC-ESTRO TAM score appears to be an important prognostic factor, assisting patients and physicians in the decision-making process.
CRIS-Team Scopus Importer:2023-08-11

Seed-displacements in the immediate post-implant phase in permanent prostate brachytherapy - Karius, Andre; Schweizer, Claudia; Strnad, Vratislav; Lotter, Michael; Kreppner, Stephan; Lamrani, Allison; Fietkau, Rainer; Bert, Christoph (Radiotherapy and Oncology, 2023)
Purpose: To investigate differences in seed-displacements between the immediate post-implant phase (day 0–1) and the time to post-plan computed tomography (CT) (day 1–30) in seed prostate brachytherapy. Materials and methods: Seed positions were identified on the intra-operatively created ultrasound-based treatment plan (day 0) and CT scans of day 1 and 30 for 33 patients. The day 1 (30) seed arrangement was registered onto the day 0 (1) arrangement using a seed-only approach. Based on a 1:1 assignment of seeds via the Kuhn-Munkres algorithm, seed-displacements were analyzed. Displacements were evaluated depending on strand-length and anatomical implant location. Resulting dosimetric effects were calculated. Results: Seed-displacements in the immediate post-implant phase (median displacements: 3.8 ± 3.6 mm) were stronger than in the time to post-plan CT (2.1 ± 2.6 mm) and enhanced along the superior-inferior direction. From day 0 to 1, strands containing one (7.3 ± 5.4 mm) or two (8.1 ± 5.8 mm) seeds showed larger displacements than strands of higher lengths (up to 4.2 ± 7.0 mm), whereas no length-dependency was found to day 30. Seeds implanted in base and apex tended to move towards the prostate midzone during both time periods. D90 (dose that 90% of prostate receives) was with variations of 2 ± 15 Gy more stable from day 1 to 30 than in the immediate post-implant phase (−18 ± 11 Gy). Conclusion: Seed-displacements in the immediate post-implant phase was enhanced compared to day 1–30. This may result from uncertainties in the gold-standard ultrasound-based treatment planning and implantation. Adaptive implantation workflows appear useful for ensuring high implant stability from the beginning.
CRIS-Team Scopus Importer:2023-03-17
Keywords: Adaptive implantation; Permanent implant; Prostate brachytherapy; Prostate cancer; Seed brachytherapy; Seed displacements

Selection of appropriate end-points (pCR vs 2yDFS) for tailoring treatments with prediction models in locally advanced rectal cancer - Valentini, Vincenzo; Van Stiphout, Ruud G. P. M.; Lammering, Guido; Gambacorta, Maria A.; Barba, Maria C.; Bebenek, Marek; Bonnetain, Franck; Bosset, Jean F.; Bujko, Krzysztof; Cionini, Luca; Gerard, Jean P.; Rödel, Claus; et al. (Radiotherapy and Oncology, 2015)
Personalized treatments based on predictions for patient outcome require early characterization of a rectal cancer patient's sensitivity to treatment. This study has two aims: (1) identify the main patterns of recurrence and response to the treatments (2) evaluate pathologic complete response (pCR) and two-year disease-free survival (2yDFS) for overall survival (OS) and their potential to be relevant intermediate endpoints to predict.Pooled and treatment subgroup analyses were performed on five large European rectal cancer trials (2795 patients), who all received long-course radiotherapy with or without concomitant and/or adjuvant chemotherapy. The ratio of distant metastasis (DM) and local recurrence (LR) rates was used to identify patient characteristics that increase the risk of recurrences.The DM/LR ratio decreased to a plateau in the first 2 years, revealing it to be a critical follow-up period. According to the patterns of recurrences, three patient groups were identified: 5-15% had pCR and were disease free after 2 years (excellent prognosis), 65-75% had no pCR but were disease free (good prognosis) and 15-30% had neither pCR nor 2yDFS (poor prognosis).Compared with pCR, 2yDFS is a stronger predictor of OS. To adapt treatment most efficiently, accurate prediction models should be developed for pCR to select patients for organ preservation and for 2yDFS to select patients for more intensified treatment strategies.
EVALuna2:18273

Senescence Induction by Combined Ionizing Radiation and DNA Damage Response Inhibitors in Head and Neck Squamous Cell Carcinoma Cells - Dobler, Clara; Jost, Tina; Hecht, Markus; Fietkau, Rainer; Distel, Luitpold (Cells, 2020)
DNA damage response inhibitors (DDRi) may selectively enhance the inactivation of tumor cells in combination with ionizing radiation (IR). The induction of senescence may be the key mechanism of tumor cell inactivation in this combinatorial treatment. In the current study the effect of combined IR with DDRi on the induction of senescence was studied in head and neck squamous cell carcinoma (HNSCC) cells with different human papilloma virus (HPV) status. The integrity of homologous recombination (HR) was assessed in two HPV positive, two HPV negative HNSCC, and two healthy fibroblast cell cultures. Cells were treated with the DDRi CC-115 (DNA-dependent protein kinase, DNA-pK; dual mammalian target of rapamycin, mTor), VE-822 (ATR; ataxia telangiectasia and Rad3-related kinase), and AZD0156 (ATM; ataxia telangiectasia mutated kinase) combined with IR. Effects on senescence, apoptosis, necrosis, and cell cycle were analyzed by flow cytometry. The fibroblast cell lines generally tolerated IR or combined treatment better than the tumor cell lines. The ATM and ATR inhibitors were effectively inducing senescence when combined with IR. The DNA-PK inhibitor was not an important inductor of senescence. HPV status and HR activity had a limited influence on the efficacy of DDRi. Induction of senescence and necrosis varied individually among the cell lines due to molecular heterogeneity and the involvement of DNA damage response pathways in senescence induction.
CRIS-Team Scopus Importer:2020-10-30
Keywords: ATM; ATR; DNA damage response inhibitor; DNAPK; HNSCC; homologous recombination; ionizing radiation; kinase inhibitor; radiosensitivity; senescence

Serial Radon Baths induce Immune and pain modulating Effects - Results of the Placebo-controlled RAD-ON02 Study - Donaubauer, Anna-Jasmina; Becker, Ina; Weikl, Lena; Klein, G.; Fournier, C.; Fietkau, Rainer; Frey, Benjamin; Gaipl, Udo (STRAHLENTHERAPIE UND ONKOLOGIE, 2022)
CRIS-Team WoS Importer:2022-06-03

Shift of radiotherapy use during the first wave of the COVID-19 pandemic? An analysis of German inpatient data - Medenwald, Daniel; Brunner, Thomas; Christiansen, Hans; Kisser, Ulrich; Mansoorian, Sina; Vordermark, Dirk; Prokosch, Hans-Ulrich; Seuchter, Susanne A.; Kapsner, Lorenz (Strahlentherapie und Onkologie, 2022)
Objective: To assess the change in inpatient radiotherapy related to COVID-19 lockdown measures during the first wave of the pandemic in 2020. Methods: We included cases hospitalized between January 1 and August 31, 2018–2020, with a primary ICD-10 diagnosis of C00–C13, C32 (head and neck cancer, HNC) and C53 (cervical cancer, CC). Data collection was conducted within the Medical Informatics Initiative. Outcomes were fractions and admissions. Controlling for decreasing hospital admissions during holidays, calendar weeks of 2018/2019 were aligned to Easter 2020. A lockdown period (LP; 16/03/2020–02/08/2020) and a return-to-normal period (RNP; 04/05/2020–02/08/2020) were defined. The study sample comprised a control (admission 2018/19) and study cohort (admission 2020). We computed weekly incidence and IR ratios from generalized linear mixed models. Results: We included 9365 (CC: 2040, HNC: 7325) inpatient hospital admissions from 14 German university hospitals. For CC, fractions decreased by 19.97% in 2020 compared to 2018/19 in the LP. In the RNP the reduction was 28.57% (p < 0.001 for both periods). LP fractions for HNC increased by 10.38% (RNP: 9.27%; p < 0.001 for both periods). Admissions for CC decreased in both periods (LP: 10.2%, RNP: 22.14%), whereas for HNC, admissions increased (LP: 2.25%, RNP: 1.96%) in 2020. Within LP, for CC, radiotherapy admissions without brachytherapy were reduced by 23.92%, whereas surgery-related admissions increased by 20.48%. For HNC, admissions with radiotherapy increased by 13.84%, while surgery-related admissions decreased by 11.28% in the same period. Conclusion: Related to the COVID-19 lockdown in an inpatient setting, radiotherapy for HNC treatment became a more frequently applied modality, while admissions of CC cases decreased.
CRIS-Team Scopus Importer:2022-01-21
Keywords: Admissions; Covid-19 pandemic; Germany; Lockdown; Radiotherapy

Shifts in Macrophage as a prognostic Biomarker in Patients with luminal Breast Cancer - A Confirmatory Study - Schnellhardt, Sören; Segelhorst, Sarah; Erber, Ramona; Daniel, Christoph; Hartmann, Arndt; Fasching, Peter; Beckmann, Matthias; Fietkau, Rainer; Distel, Luitpold; Rübner, Matthias (STRAHLENTHERAPIE UND ONKOLOGIE, 2021)
CRIS-Team WoS Importer:2021-07-16

Should salvage surgery be considered for local recurrence after definitive chemoradiation in locally advanced non-small cell lung cancer? - Schreiner, Waldemar; Dudek, Wojciech; Lettmaier, Sebastian; Fietkau, Rainer; Sirbu, Horia (Journal of Cardiothoracic Surgery, 2016)
Incidence of local relapse after definitive chemoradiation (>59 Gy) for locally advanced non-small-cell lung cancer (NSCLC) is high, irrespective of high dose radiation applied. Experience with salvage lung resections in patients with locally relapsed NSCLC after definitive chemoradiation is limited. We present our series of salvage lung resections for local NSCLC relapse after curative-intent chemoradiation for locally advanced tumor.Nine consecutive patients with local tumor recurrence or persistence following definitive chemoradiation were reviewed. Kaplan-Meier analysis was used to assess patient survival.All patients received definitive radiation (median dose 66.2 Gy) with concurrent chemotherapy. Tumor stage prior to chemoradiation was IIIA in 8 patients and IV in 1. In 4 patients tumor invaded the chest wall, in 2 the spine and in 1 the aorta. Median interval between chemoradiation and salvage resection was 30.2 weeks. Nine patients underwent 9 resections (6 lobectomies, 1 bilobectomy, 1 pneumonectomy and 1 bi-segmentectomy). One death occurred on the 12th postoperative day. Median overall survival was 23 months; postoperative 3-year survival was 47 %. Median progression-free survival was 21 months.Salvage lung resection for locally recurrent or persisted NSCLC in selected patients with locally advanced NSCLC following definitive chemoradiation is a worthwhile treatment option.
EVALuna2:18249

Simultaneous amniotic membrane patch in high-risk keratoplasty - Seitz, Berthold; Das, Sujata; Sauer, Rolf; Hofmann-Rummelt, Carmen; Beckmann, Matthias; Kruse, Friedrich (Cornea, 2011)
To analyze the short- and intermediate-term results of simultaneous transplantation of amniotic membrane with high-risk keratoplasty.Between January 2002 and February 2004, a simultaneous amniotic membrane patch was transplanted with penetrating keratoplasty in 16 eyes of 16 patients. In 13 eyes, a soft contact lens was applied afterward. Corneal perforation was present in 10 of 14 eyes with emergency keratoplasty. Five patients received systemic immunosuppressive medication for 4-6 months after penetrating keratoplasty.The amniotic membrane patch fell off after 8 ± 3 (range: 4-14) days without residual tissue except in 1 case. In 15 of 16 eyes, the epithelium was completely closed after 10 ± 8 (range: 4-30) days. In 3 eyes, recurrence of the epithelial defect occurred after 3-6 months. During a follow-up period of 18 ± 6 months, 13 of 16 corneal grafts were clear.Simultaneous amniotic membrane transplantation and penetrating keratoplasty may improve the prognosis of corneal graft in eyes with risk of epithelial healing problems.
EVALuna2:17178

Single-cycle induction chemotherapy before chemoradiotherapy or surgery in functionally inoperable head and neck squamous cell carcinoma: 10-year results - Breheret, Marius; Lubgan, Dorota; Haderlein, Marlen; Hecht, Markus; Traxdorf, Maximilian; Schmidt, Daniela; Mueller, Sarina K.; Kitzsteiner, Christian; Kuwert, Torsten; Iro, Heinrich; Fietkau, Rainer; Semrau, Sabine (European Archives of Oto-Rhino-Laryngology, 2019)
Introduction The response to induction chemotherapy (IC) predicts local control after conservative treatment of laryngeal, meso- and hypopharyngeal head and neck squamous cell carcinoma (HNSCC) and can thus help to avoid surgery. Single-cycle induction chemotherapy may help to maintain a low local recurrence rate while keeping the overall toxicity manageable. However, long-term data on single-cycle IC response by tumor location is lacking. Methods N = 102 patients with functionally inoperable primary HNSCC of the larynx (n = 43), hypopharynx (n = 42) or mesopharynx/tongue (n = 17) received one cycle of docetaxel (75 mg/m(2), d1) plus cisplatin (30 mg/m(2), d1-3) or carboplatin (AUC 1.5, d1-3) and a response evaluation 3 weeks later. Responders (>= 30% tumor size reduction and >= 20% SUVmax decrease in F-18-FDG PET/CT) were recommended chemoradiotherapy (CRT), and non-responders surgery. Results The overall response rate was 72.5%. All 74 responders and 10 non-responders received primary CRT, and 18 patients received primary surgery after single-cycle IC. Overall 10-year local recurrence-free survival (LRFS) was 73.7%. Three-year LRFS was 88.2% (mesopharynx/tongue), 88.2% (larynx), and 73.3% (hypopharynx); p = 0.17. 3-year distant metastasis-free survival (DMFS) was 94.1% (mesopharynx/tongue), 88.0% (larynx) and 76.4% (hypopharynx); p > 0.05. This influenced the 3-year cancer-specific survival (CSS) for larynx (91.2%) vs. hypopharynx tumors (60.8%); p = 0.003, but CSS was not different to tumors in the mesopharynx/tongue (81.4%); p > 0.05. Conclusions A single-cycle induction chemotherapy for HNSCC enables surgery plus adjuvant therapy as well as chemoradiotherapy. The long-term local and distant disease control was good but varied between tumors in the larynx and mesopharynx/tongue vs. hypopharynx.
CRIS-Team WoS Importer:2019-10-18

Single-cycle induction chemotherapy followed by chemoradiotherapy or surgery in patients with head and neck cancer: What are the best predictors of remission and prognosis? - Semrau, Sabine; Haderlein, Marlen; Schmidt, Daniela; Lell, Michael; Wolf, Walburga; Waldfahrer, Frank; Uder, Michael; Iro, Heinrich; Kuwert, Torsten; Fietkau, Rainer (Cancer, 2015)
There is controversy over the concept of function and organ preservation by chemotherapy/chemoradiation instead of surgery in locally advanced cancer of the larynx or pharynx. Tumor response to induction chemotherapy (ICT) can help in choosing between conservative and surgical treatment. This study compared 3 methods of assessing response to ICT: endoscopy, computed tomography, and (18) F-FDG-PET/CT.Primary response to 1 cycle of ICT with docetaxel plus platinum was assessed by the aforementioned methods in 62 laryngopharyngeal cancer patients. Endoscopic response was the deciding factor for selecting further treatment: surgery for endoscopic nonresponders (<30% tumor response) versus chemoradiotherapy for endoscopic responders.ICT achieved endoscopic response in 48 of 62 patients (77%). Individual relative residual tumor activity of standardized uptake value (resSUVmax ) in (18) F-FDG-PET/CT was a median 0.38 of baseline (0.09-1.71), whereas residual tumor extent in CT (resCT) was 0.75 of baseline (0.32-1.20). Endoscopic responders and nonresponders differed significantly in SUVmax after ICT (postSUVmax , 6.0 vs 14.5; P < .001), resSUVmax (0.34 vs 0.81, P < .001), and resCT (0.71 vs 0.87, P = .004), but not in maximum tumor diameter after ICT (14 vs 20 mm, P = .11). resSUVmax <0.8 and absolute postSUVmax <10 provided the best discriminatory power for long-term success criteria (tumor-free survival, overall survival).Metabolic tumor response showed very good correlation with clinical tumor response to ICT. The value of metabolic response detected by (18) F-FDG-PET/CT should be explored in a prospective clinical trial. Cancer 2015;121:1214-1222. © 2014 American Cancer Society.
EVALuna2:13821

Single cycle induction treatment with cisplatin/docetaxel plus durvalumab/tremelimumab in stage III-IVB head and neck squamous cell cancer (CheckRad-CD8 trial) - Hecht, Markus; Gostian, A-O.; Eckstein, Markus; Rutzner, Sandra; Von Der Gruen, J.; Illmer, T.; Hautmann, M. G.; Brunner, T.; Laban, S.; Klautke, G.; Tamaskovics, B.; Frey, Benjamin; et al. (ANNALS OF ONCOLOGY, 2019)
CRIS-Team WoS Importer:2019-11-08

Sinonasal Leiomyosarcoma: Clinicopathological Analysis of Nine Cases with Emphasis on Common Association with Other Malignancies and Late Distant Metastasis - Agaimy, Abbas; Semrau, Sabine; Koch, Michael; Thompson, Lester D.R. (Head and Neck Pathology, 2018)
Sinonasal tract (SNT) leiomyosarcoma (LMS) is exceedingly rare with < 100 cases reported. Their relationship to retinoblastoma and other malignancies, along with previous irradiation has not been clarified. Routine and consultation cases were reviewed for histologically and immunohistochemically proven SNT LMS. The tumors were tested with antibodies against α-smooth muscle actin, desmin, h-caldesmon, HMB45, S100 protein, Rb1, MDM2, CDK4 and EBV (EBER-ISH). Nine tumors affecting 5 males and 4 females aged 26 to 77 years (median: 48 years) were identified in the maxillary sinus (n = 4), nasal cavity (n = 3) and combined SNT (n = 2). Three patients had previous irradiation (2 for retinoblastoma, 1 for fibrous dysplasia) and 1 patient had chemotherapy and stem cell transplantation for Hodgkin lymphoma. One patient had prostatic adenocarcinoma (prior) and rectal adenocarcinoma (post) to the LMS. All patients with follow-up developed either local recurrences and/or metastases, principally to lung (time to metastasis: 16-156 months, mean 62 months). Histologically, 6 tumors were conventional high-grade LMS, two had glycogen-rich clear cell (PEComa-like) morphology and one was spindle cell low-grade. The latter showed grade 2 in the recurrence and grade 3 in the lung metastases. Two cases showed dedifferentiation to anaplastic pleomorphic (inflammatory MFH-like) phenotype. Immunohistochemistry revealed diffuse expression of at least 2 smooth muscle markers in 8 and only actin in one case/s. All other markers were negative. RB1 loss was observed in 6/8 cases tested. Sinonasal tract leiomyosarcomas are rare aggressive sarcomas that frequently develop in a background of previous cancer therapy (4/9), most frequently irradiation. Their varied morphology underlines the wide differential diagnostic considerations. Long-term survival may be achieved with aggressive multimodal therapy.
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Siponimod reduces perihemorrhagic edema and improves neurological outcome in experimental intracerebral hemorrhage - Bobinger, Tobias; Manaenko, A.; Baeurele, T.; Seyler, L.; Nagel, Armin Michael; Engelhorn, Tobias; Dörfler, Arnd; Kuramatsu, J. B.; Schwab, Stefan; Huttner, Hagen (JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 2019)
CRIS-Team WoS Importer:2019-07-19

Skin sodium content as a predictor of blood pressure response to renal denervation - Günes-Altan, Merve; Schmid, Axel; Kannenkeril, Dennis; Linz, Peter; Ott, Christian; Bosch, Agnes; Schiffer, Mario; Uder, Michael; Schmieder, Roland (Hypertension Research, 2023)
Patients with treatment resistant hypertension (TRH) are known to have elevated sodium (Na) content in muscle and skin. Renal denervation (RDN) emerged as an adjacent therapeutic option in this group of patients. This analysis aimed at evaluating whether tissue Na content predicts blood pressure (BP) response after RDN in patients with TRH. Radiofrequency-device based RDN was performed in 58 patients with uncontrolled TRH. Office and 24-h ambulatory BP were measured at baseline and after 6 months. To assess tissue Na content Na magnetic resonance imaging (Na-MRI) was performed at baseline prior to RDN. We splitted the study cohort into responders and non-responders based on the median of systolic 24-h ambulatory blood pressure (ABP) reduction after 6 months and evaluated the association between BP response to RDN and tissue Na content in skin and muscle. The study was registered at http://www.clinicaltrials.gov (NCT01687725). Six months after RDN 24-h ABP decreased by −8.6/−4.7 mmHg. BP-Responders were characterized by the following parameters: low tissue sodium content in the skin (p = 0.040), female gender (p = 0.027), intake of aldosterone antagonists (p = 0.032), high baseline 24-h night-time heart rate (p = 0.045) and high LDL cholesterol (p < 0.001). These results remained significant after adjustment for baseline 24-h systolic BP. Similar results were obtained when the median of day-time and night-time ABP reduction after 6 months were used as cut-off criteria for defining BP response to RDN. We conclude that in addition to clinical factors including baseline 24-h ABP Na-MRI may assist to select patients with uncontrolled TRH for RDN treatment. [Figure not available: see fulltext.].
CRIS-Team Scopus Importer:2023-11-03
Keywords: Renal denervation; Sodium MRI; Tissue sodium

Small oral squamous cell carcinomas with nodal lymphogenic metastasis show increased infiltration of M2 polarized macrophages - An immunohistochemical analysis - Weber, Manuel; Büttner, Maike; Hyckel, Peter; Moebius, Patrick; Distel, Luitpold; Ries, Jutta; Amann, Kerstin Ute; Neukam, Friedrich Wilhelm; Wehrhan, Falk (Journal of Cranio-Maxillofacial Surgery, 2014)
In solid malignancies the influence of immunological parameters - especially of macrophages - on invasiveness, metastatic potential and prognosis has been shown. There are no studies quantitatively analysing the macrophage polarization in oral squamous cell carcinoma (oscc). The aim of this study was to correlate macrophage polarization in the epithelial and stromal compartment of oscc with histopathologic parameters.T1 and T2 oscc samples (n = 34) were used. Automated immunohistochemical staining detected CD68, CD11c, CD163 and MRC1 positive cells. All samples were completely digitalized using whole slide imaging and the number of stained cells per area was assessed quantitatively.Primary tumours with lymphogenic metastasis (N+) showed a significantly (p < 0.05) increased count of CD68, CD11c, CD163 and MRC1 positive cells in the epithelial fraction compared to N0 tumours. The ratio of CD163 positive cells (M2 macrophages) to CD68 positive cells (M1 and M2 macrophages) was significantly (p < 0.05) increased in N+ tumours.An increased macrophage infiltration and an increased M2 polarization in primary oral squamous cell carcinomas with lymphogenic metastasis was shown. Macrophages that migrated into the epithelial tumour fraction seem to be of special biological importance. The results indicate a central role of macrophages in the progression of oscc.
EVALuna2:18151

SMARCB1(INI1)-deficient sinonasal basaloid carcinoma: a novel member of the expanding family of SMARCB1-deficient neoplasms - Agaimy, Abbas; Koch, Michael; Lell, Michael; Semrau, Sabine; Dudek, Wojciech; Wachter, David; Knöll, Antje; Iro, Heinrich; Haller, Florian; Hartmann, Arndt (American Journal of Surgical Pathology, 2014)
Poorly differentiated sinonasal carcinomas are a heterogenous group of aggressive neoplasms that encompasses squamous cell carcinoma including basaloid variant, lymphoepithelial carcinoma, sinonasal undifferentiated carcinoma, and neuroendocrine-type small cell carcinoma. We herein describe 3 cases of a hitherto unreported variant combining features of basaloid carcinoma with variable intermingled rhabdoid cells. Patients were 2 women (aged 28 and 35) and a man (52 y) who presented with sinonasal masses. All had advanced local disease with bone involvement (pT4). None had a history of irradiation or a family history of rhabdoid tumors. Treatment was surgery and adjuvant chemoradiation. One patient developed liver, lung, pleural, and pericardial metastases (63 mo) and is currently (70 mo) alive under palliative treatment. Another developed recurrent cervical lymph node metastases and died of disease 8.5 years later. The youngest patient was disease-free at last follow-up 7 years later. Histologic features were very similar in all 3 cases and showed intimate admixture of compact basaloid cell nests with peripheral palisading, perivascular pseudorosettes, and a few scattered rhabdoid cells. Rhabdoid cells were more extensive in the metastasis in 1 case but formed a minor inconspicuous component in the primary tumors in all cases. Striking features common to all cases were (1) basaloid "blue" appearance at low power, (2) papilloma-like exophytic component, (3) extensive pagetoid surface growth with prominent denuding features, and (4) replacement of underlying mucous glands mimicking an inverted papilloma. Clear-cut origin from benign papilloma and overt squamous differentiation were lacking. Diffuse (2) or partial (1) p16 expression was noted, but all cases lacked human papillomavirus DNA by molecular tests. In situ hybridization was negative for Epstein-Barr virus. Immunohistochemistry showed diffuse expression of pancytokeratin. CK5 and vimentin showed intermingling of CK5/vimentin basaloid and CK5/vimentin rhabdoid cells. Complete loss of nuclear SMARCB1 expression was seen in all cases including also the denuding carcinoma in situ-like surface lesions. To our knowledge, this variant of sinonasal carcinoma has not been reported before. The identical features in all 3 cases suggest a specific disease rather than a nonspecific dedifferentiated phenotype. Awareness of this rare variant and thus reporting of additional cases is necessary for defining its full morphologic and biological spectrum.
EVALuna2:6600

SMARCB1 (INI-1)-deficient Sinonasal Carcinoma: A Series of 39 Cases Expanding the Morphologic and Clinicopathologic Spectrum of a Recently Described Entity - Agaimy, Abbas; Hartmann, Arndt; Antonescu, Cristina R.; Chiosea, Simion I.; El-Mofty, Samir K.; Geddert, Helene; Iro, Heinrich; Lewis, James S.; Markl, Bruno; Mills, Stacey E.; Riener, Marc-Oliver; Robertson, Thomas; et al. (American Journal of Surgical Pathology, 2017)
To more fully characterize the clinical and pathologic spectrum of a recently described tumor entity of the sinonasal tract characterized by loss of nuclear expression of SMARCB1 (INI1), we analyzed 39 SMARCB1-deficient sinonasal carcinomas collected from multiple medical centers. The tumors affected 23 males and 16 females with an age range of 19 to 89 years (median, 52). All patients presented with locally advanced disease (T3, n=5; T4, n=27) involving the sinuses (mainly ethmoid) with variable involvement of the nasal cavity. Thirty patients received surgery and/or radiochemotherapy with curative intent. At last follow-up, 56% of patients died of disease 0 to 102 months after diagnosis (median, 15), 2 were alive with disease, and 1 died of an unrelated cause. Only 9 patients (30%) were alive without disease at last follow-up (range, 11 to 115 mo; median, 26). The original diagnosis of retrospectively identified cases was most often sinonasal undifferentiated carcinoma (n=14) and nonkeratinizing/basaloid squamous cell carcinoma (n=5). Histologically, most tumors displayed either a predominantly basaloid (61%) or plasmacytoid/rhabdoid morphology (36%). The plasmacytoid/rhabdoid form consisted of sheets of tumor cells with abundant, eccentrically placed eosinophilic cytoplasm, whereas similar cells were typically rare and singly distributed in the basaloid variant. Glandular differentiation was seen in a few tumors. None of the cases showed squamous differentiation or surface dysplasia. By immunohistochemistry, the tumors were positive for pancytokeratin (97%), CK5 (64%), p63 (55%), and CK7 (48%); and they were negative for NUT (0%). Epstein-Barr virus and high-risk human papillomavirus was not detected by in situ hybridization. Immunohistochemical loss of SMARCB1 (INI1) expression was confirmed for all 39 tumors. Investigation of other proteins in the SWI/SNF complex revealed co-loss of SMARCA2 in 4 cases, but none were SMARCA4 deficient or ARID1A deficient. Of 27 tumors with SMARCB1 fluorescence in situ hybridization analysis, 14 showed homozygous (biallelic) deletions and 7 showed heterozygous (monoallelic) deletions. SMARCB1-deficient sinonasal carcinoma represents an emerging poorly differentiated/undifferentiated sinonasal carcinoma that (1) cannot be better classified as another specific tumor type, (2) has consistent histopathologic findings (albeit with some variability) with varying proportions of plasmacytoid/rhabdoid cells, and (3) demonstrates an aggressive clinical course. This entity should be considered in any difficult-to-classify sinonasal carcinoma, as correct diagnosis will be mandatory for optimizing therapy and for further delineation of this likely underdiagnosed disease.
EVALuna2:6856

Spatial distribution of FoxP3+ and CD8+ tumour infiltrating T cells reflects their functional activity - Posselt, Rebecca; Erlenbach-Wuensch, Katharina; Haas, Matthias; Jeßberger, Jonas; Buettner-Herold, Maike; Haderlein, Marlen; Hecht, Markus; Hartmann, Arndt; Fietkau, Rainer; Distel, Luitpold (Oncotarget, 2016)
Regulatory and cytotoxic T cells are key players in the host's anticancer immune response. We studied the spatial distribution of FoxP+ and CD8+ cells to identify potential interactions.In 202 patients 103 pre-radiochemotherapy biopsies and 153 post-radiochemotherapy tumour specimens of advanced rectal cancer were available and an immunohistochemical double staining of FoxP3+ and CD8+ tumour-infiltrating lymphocytes was performed to investigate cell density and cell-to-cell distances.FoxP3+ cells decreased after radiochemotherapy by a factor of 3 while CD8+ cells remained nearly unchanged. High epithelial (p=0.033) and stromal (p=0.009) FoxP3+ cell density was associated with an improved overall survival. Cell-to-cell distances of randomly distributed cells were simulated and compared to observed cell-to-cell distances. Observed distances shorter than the simulated, random distances were hypothesized to represent FoxP3+ cells actively interacting with CD8+ cells. Epithelial short distances were associated with a favourable prognosis while the opposite was true for the stromal compartment.The analysis of cell-to-cell distances may offer a tool to predict outcome, maybe by identifying functionally active, interacting infiltrating inflammatory cells in different tumour compartments.
EVALuna2:6815

Spatial Distribution of Inflammatory Cells and their Interactions in Pancreatic Carcinoma Tissues of 63 Patients - Distel, Luitpold; Zoske, Hanno; Fietkau, Rainer; Hecht, Markus (2017)
EVALuna2:32879

Specific Effect of BRAF-Inhibitors on a BRAF-mutant and a Wild-type Cell Line of Malignant Melanoma - Steck, M.; Grabenbauer, Maximilian; Fünfle, Ruben; Hecht, Markus; Fietkau, Rainer; Distel, Luitpold (2017)
EVALuna2:32896

Sporadic endolymphatic sac tumor–a diagnostic and therapeutic challenge - Kuenzel, Julian; Agaimy, Abbas; Hornung, Joachim; Lell, Michael; Ganslandt, Oliver Thomas; Semrau, Sabine; Zenk, Johannes (International Journal of Clinical and Experimental Pathology, 2014)
Endolymphatic sac tumor (ELST) is a rare low-grade locally aggressive neoplasm of the inner ear that may occur sporadically or in the setting of von Hippel-Lindau syndrome. We herein present a case of sporadic ELST in a 39-year-old man, treated using an interdisciplinary approach (surgery+radiotherapy), with a 10-year follow-up. The patient presented with hearing loss of sudden onset. The treatment of choice for ELST is radical tumor resection, which is associated with a good long-term prognosis. Remission may last for years, but there may be local recurrences, probably as a result of incomplete resection. Adjuvant radiotherapy is an option in case of recurrence and could be discussed after incomplete resection. The purpose of this report is to call attention to ELSTs, which are difficult to diagnose due to their rarity and variety of presentations.
EVALuna2:6593

Stage-Dependent Frequency of Lymph Node Metastases in Patients With Rectal Carcinoma After Preoperative Chemoradiation: Results from the CAO/ARO/AIO-94 Trial and From a Comparative Prospective Evaluation With Extensive Pathological Workup - Sprenger, Thilo; Rothe, Hilka; Conradi, Lena-Christin; Beissbarth, Tim; Kauffels, Anne; Kitz, Julia; Homayounfar, Kia; Wolff, Hendrik; Stroebel, Philipp; Ghadimi, Michael; Wittekind, Christian; Sauer, Rolf; et al. (Diseases of the colon & rectum, 2016)
For patients with ycT1/2 rectal carcinomas after neoadjuvant chemoradiotherapy, local excision instead of radical surgery has increasingly been discussed as a way to avoid postoperative morbidity associated with radical surgery.The purpose of this study was to determine the incidence of lymph node metastases in total mesorectal excision specimens with ypT0, ypT1/2, and ypT3/4 rectal cancers.This is a prospective and retrospective cohort study.This study was conducted in tertiary referral hospitals that are part of the German Rectal Cancer Study Group.A total of 479 patients with stage II and III rectal cancers treated within phase III trials of the German Rectal Cancer Study Group were evaluated. Specimens from 81 patients treated in the Working Group of Surgical Oncology/Working Group of Radiation Oncology/Working Group of Medical Oncology of the Germany Cancer Society (CAO/ARO/AIO-04) trial were prospectively studied with extensive microscopic screening of the entire mesorectum. The frequency and localization of nodal metastases were specified and compared with those of 398 patients having received neoadjuvant chemoradiation within the CAO/ARO/AIO-94 trial.Frequency and localization of mesorectal lymph node metastases in patients with ypT0, ypT1/2, or ypT3/4 cancer were measured.A mean number of 28.0 ± 13.7 nodes were detected per specimen within the prospective group. A total of 25% of patients in the ypT1/2 group had nodal metastases compared with 40% in the ypT3/4 group. Patients with node-positive ypT1/2 had a mean number of 2.2 metastases, and 55% of these metastases were located far from the primary lesion in the proximal mesorectum. Within the CAO/ARO/AIO-94 cohort (n = 398), 19% of patients with ypT1/2 (ypT1 = 22%; ypT2 = 18%) had ypN+ status compared with 43% with ypT3/4 cancers (ypT3 = 40%; ypT4 = 73%).Low numbers of patients with ypT0 limited the evaluation of nodal metastases in pathologic complete responders.Even in good responders (ypT1/2), >20% of rectal carcinomas still harbored residual lymph node metastases. Local excision for patients with ycT1/2 rectal cancers would, thus, miss metastases in a considerable percentage and might involve the risk of significant undertreatment in a number of patients.
EVALuna2:18337

Static and Dynamic, but not Pulsed High-Pressure Treatment Efficiently Inactivates Yeast - Izydor, Marika; Hainthaler, Markus; Gaipl, Udo; Frey, Benjamin; Schlücker, Eberhard (Chemical Engineering & Technology, 2017)
Static high-pressure (HP) treatment has become a powerful tool for preserving foodstuffs, allowing high inactivation rates and minimal adverse effects on valuable components. Due to HP maxima and batch mode conditions, it is restricted to high-grade products. To overcome these restrictions, dynamic HP offers the possibility of a quasi-continuous mode of operation. The effects of three different HP treatments (static, pulsed, and dynamic) on yeast were investigated. The inactivation efficiency and membrane damage increase with increasing pressure or pressure holding time. The cells do not show higher sensitivity to fast and repeated depressurization, and the number of pressure pulses plays only a minor role in inducing membrane damage. A form of programmed cell death could not be detected.
EVALuna2:32933

Status epilepticus in patients with glioblastoma: Clinical characteristics, risk factors, and epileptological outcome - Stritzelberger, Jenny; Gesmann, Anna; Fuhrmann, Imke; Balk, Stefanie; Reindl, Caroline; Madzar, Dominik; Uhl, Martin; Welte, Tamara; Brandner, Sebastian; Eisenhut, Felix; Dörfler, Arnd; Coras, Roland; et al. (Seizure-European Journal of Epilepsy, 2023)
Purpose: Epilepsy is a common comorbidity in patients with glioblastoma, however, clinical data on status epilepticus (SE) in these patients is sparse. We aimed to investigate the risk factors associated with the occurrence and adverse outcomes of SE in glioblastoma patients. Methods: We retrospectively analysed electronic medical records of patients with de-novo glioblastoma treated at our institution between 01/2006 and 01/2020 and collected data on patient, tumour, and SE characteristics. Results: In the final cohort, 292/520 (56.2 %) patients developed seizures, with 48 (9.4 % of the entire cohort and 16.4 % of patients with epilepsy, PWE) experiencing SE at some point during the course of their disease. SE was the first symptom of the tumour in 6 cases (1.2 %) and the first manifestation of epilepsy in 18 PWE (6.2 %). Most SE episodes occurred postoperatively (n = 37, 77.1 %). SE occurrence in PWE was associated with postoperative seizures and drug-resistant epilepsy. Adverse outcome (in-house mortality or admission to palliative care, 10/48 patients, 20.8 %), was independently associated with higher status epilepticus severity score (STESS) and Charlson Comorbidity Index (CCI), but not tumour progression. 32/48 SE patients (66.7 %) were successfully treated with first- and second-line agents, while escalation to third-line agents was successful in 6 (12.5 %) cases. Conclusion: Our data suggests a link between the occurrence of SE, postoperative seizures, and drug-resistant epilepsy. Despite the dismal oncological prognosis, SE was successfully treated in 79.2 % of the cases. Higher STESS and CCI were associated with adverse SE outcomes.
CRIS-Team Scopus Importer:2023-09-29
Keywords: Glioblastoma; Status epilepticus; Status epilepticus severity score (STESS)

Stereotactic body radiotherapy of adrenal metastases-A dose-finding study - Buergy, Daniel; Wuerschmidt, Florian; Gkika, Eleni; Hoerner-Rieber, Juliane; Knippen, Stefan; Gerum, Sabine; Balermpas, Panagiotis; Henkenberens, Christoph; Voglhuber, Theresa; Kornhuber, Christine; Barczyk, Steffen; Roeper, Barbara; et al. (International Journal of Cancer, 2022)
Optimal doses for the treatment of adrenal metastases with stereotactic radiotherapy (SBRT) are unknown. We aimed to identify dose-volume cut-points associated with decreased local recurrence rates (LRR). A multicenter database of patients with adrenal metastases of any histology treated with SBRT (biologically effective dose, BED10 >= 50 Gy, <= 12 fractions) was analyzed. Details on dose-volume parameters were required (planning target volume: PTV-D98%, PTV-D50%, PTV-D2%; gross tumor volume: GTV-D50%, GTV-mean). Cut-points for LRR were optimized using the R maxstat package. One hundred and ninety-six patients with 218 lesions were included, the largest histopathological subgroup was adenocarcinoma (n = 101). Cut-point optimization resulted in significant cut-points for PTV-D50% (BED10: 73.2 Gy; P = .003), GTV-D50% (BED10: 74.2 Gy; P = .006), GTV-mean (BED10: 73.0 Gy; P = .007), and PTV-D2% (BED10: 78.0 Gy; P = .02) but not for the PTV-D98% (P = .06). Differences in LRR were clinically relevant (LRR >= doubled for cut-points that were not achieved). Further dose-escalation was not associated with further improved LRR. PTV-D50%, GTV-D50%, and GTV-mean cut-points were also associated with significantly improved LRR in the adenocarcinoma subgroup. Separate dose optimizations indicated a lower cut-point for the PTV-D50% (BED10: 69.1 Gy) in adenocarcinoma lesions, other values were similar (<2% difference). Associations of cut-points with overall survival (OS) and progression-free survival were not significant but durable freedom from local recurrence was associated with OS in a landmark model (P < .001). To achieve a significant improvement of LRR for adrenal SBRT, a moderate escalation of PTV-D50% BED10 >73.2 Gy (adenocarcinoma: 69.1 Gy) should be considered.
CRIS-Team WoS Importer:2022-04-29

Stereotactic or conformal radiotherapy for adrenal metastases: Patient characteristics and outcomes in a multicenter analysis - Buergy, Daniel; Wuerschmidt, Florian; Gkika, Eleni; Hoerner-Rieber, Juliane; Knippen, Stefan; Gerum, Sabine; Balermpas, Panagiotis; Henkenberens, Christoph; Voglhuber, Theresa; Kornhuber, Christine; Barczyk, Steffen; Roeper, Barbara; et al. (International Journal of Cancer, 2021)
To report outcome (freedom from local progression [FFLP], overall survival [OS] and toxicity) after stereotactic, palliative or highly conformal fractionated (>12) radiotherapy (SBRT, Pall-RT, 3DCRT/IMRT) for adrenal metastases in a retrospective multicenter cohort within the framework of the German Society for Radiation Oncology (DEGRO). Adrenal metastases treated with SBRT (<= 12 fractions, biologically effective dose [BED10] >= 50 Gy), 3DCRT/IMRT (>12 fractions, BED10 >= 50 Gy) or Pall-RT (BED10 < 50 Gy) were eligible for this analysis. In addition to unadjusted FFLP (Kaplan-Meier/log-rank), we calculated the competing-risk-adjusted local recurrence rate (CRA-LRR). Three hundred twenty-six patients with 366 metastases were included by 21 centers (median follow-up: 11.7 months). Treatment was SBRT, 3DCRT/IMRT and Pall-RT in 260, 27 and 79 cases, respectively. Most frequent primary tumors were non-small-cell lung cancer (NSCLC; 52.5%), SCLC (16.3%) and melanoma (6.7%). Unadjusted FFLP was higher after SBRT vs Pall-RT (P = .026) while numerical differences in CRA-LRR between groups did not reach statistical significance (1-year CRA-LRR: 13.8%, 17.4% and 27.7%). OS was longer after SBRT vs other groups (P < .05) and increased in patients with locally controlled metastases in a landmark analysis (P < .0001). Toxicity was mostly mild; notably, four cases of adrenal insufficiency occurred, two of which were likely caused by immunotherapy or tumor progression. Radiotherapy for adrenal metastases was associated with a mild toxicity profile in all groups and a favorable 1-year CRA-LRR after SBRT or 3DCRT/IMRT. One-year FFLP was associated with longer OS. Dose-response analyses for the dataset are underway.
CRIS-Team WoS Importer:2021-04-02

Stereotactic radiotherapy as primary definitive or postoperative treatment of intracranial meningioma of WHO grade II and III leads to better disease control than stereotactic radiotherapy of recurrent meningioma - Lubgan, Dorota; Rutzner, Sandra; Lambrecht, Ulrike; Roessler, Karl; Buchfelder, Michael; Eyüpoglu, Ilker Yasin; Fietkau, Rainer; Semrau, Sabine (Journal of Neuro-Oncology, 2017)
The aim of this study was to evaluate long-term clinical outcome, prognostic factors and quality of life after adjuvant or definitive fractionated stereotactic radiotherapy (SRT) of meningioma WHO grade II and III or at recurrence. 131 patients with 138 meningioma (64 WHO grade II, 16 WHO grade III, 58 without histology) of the skull base, falx and convexity were treated between 01/2002 and 01/2015 at the Erlangen University Hospital by fractionated stereotactic radiotherapy (SRT) as primary treatment (adjuvant or definitive) and at recurrence. 53% (n = 53) lesions of patients with primary tumour received postoperative SRT and 47% (n = 47) as definitive treatment (without surgery). All 38 lesions (100%) of recurrent meningioma underwent surgery followed by SRT. SRT was mostly given in 28, 30 or 25 fractions to a median dose of 54.0 Gy in the reference point. Progression-free-survival at 8 years for patients with meningioma at primary treatment were significantly better with 100% for patients with definitive SRT (p = 0.008) or 85% for patients with adjuvant SRT (p = 0.009) compared to 42% after treatment (surgery + SRT) of recurrence. Progression-free-survival at 8 years for patients with SRT as adjuvant treatment after gross total resection of WHO grade II meningioma were significantly better at 83% (p = 0.016) compared to 46% after adjuvant SRT of recurrence. In 31% of patients after primary treatment and in 38.5% after recurrence treatment an improvement of pain symptoms was achieved. The favourable prognostic factor for better PFS at recurrence treatment was tumor location (skull base or convexity better compared to the falx). Postoperative SRT of WHO grade II meningioma after gross total resection (GTR) can effectively reduce recurrence risk.
EVALuna2:32870

Stereotactic radiotherapy of vestibular schwannoma : Hearing preservation, vestibular function, and local control following primary and salvage radiotherapy - Putz, Florian; Müller, Jan; Wimmer, Cornelia; Goerig, Nicole; Knippen, Stefan; Iro, Heinrich; Grundtner, Philipp; Eyüpoglu, Ilker Yasin; Roessler, Karl; Semrau, Sabine; Fietkau, Rainer; Lettmaier, Sebastian (Strahlentherapie und Onkologie, 2017)
OBJECTIVE: The aim of this publication is to present long-term data on functional outcomes and tumor control in a cohort of 107 patients treated with stereotactic radiotherapy (RT) for vestibular schwannoma. PATIENTS AND METHODS: Included were 107 patients with vestibular schwannoma (primary or recurrent following resection) treated with stereotactic RT (either fractioned or single-dose radiosurgery) between October 2002 and December 2013. Local control and functional outcomes were determined. Analysis of hearing preservation was limited to a subgroup of patients with complete audiometric data collected before treatment and during follow-up. Vestibular function test (FVT) results could be analyzed in a subset of patients and were compared to patient-reported dizziness. RESULTS: After a mean follow-up of 46.3 months, actuarial local control for the whole cohort was 100% after 2, 97.6% after 5, and 94.1% after 10 years. In patients with primary RT, serviceable hearing was preserved in 72%. Predictors for preservation of serviceable hearing in multivariate analysis were time of follow-up (odds ratio, OR = 0.93 per month; p = 0.021) and pre-RT tumor size (Koos stage I-IIa vs. IIb-IV; OR = 0.15; p = 0.031). Worsening of FVT results was recorded in 17.6% (N = 3). Profound discrepancy of patient-reported dizziness and FVT results was observed after RT. In patients with primary RT, worsening of facial nerve function occurred in 1.7% (N = 1). CONCLUSION: Stereotactic RT of vestibular schwannoma provides good functional outcomes and high control rates. Dependence of hearing preservation on time of follow-up and initial tumor stage has to be considered.
EVALuna2:32910

Stereotaktisch ablative Bestrahlung als Standardtechnik beim NSCLC im Stadium I bestätigt - Hecht, Markus; Fietkau, Rainer (Strahlentherapie und Onkologie, 2019)
CRIS-Team Scopus Importer:2019-10-08

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)
The objectives of this study were the evaluation of flexor tendon pulley rupture of the fingers in the crimp grip position using magnetic resonance imaging (MRI) and the comparison of the results with MRI in the neutral position in a cadaver study.MRI in the crimp grip position and in the neutral position was performed in 21 cadaver fingers with artificially created flexor tendon pulley tears (combined pulley rupture, n = 14; single pulley rupture, n = 7). Measurement of the distance between the tendon and bone was performed. Images were evaluated by two readers, first independently and in cases of discrepancy in consensus. Sensitivity and specificity for detecting combined pulley ruptures were calculated.Tendon bone distances were significantly higher in the crimp grip position than in the neutral position. Sensitivity and specificity for detecting combined pulley rupture were 92.86 % and 100 % respectively in the crimp grip position and 78.57 % and 85.71 % respectively in the neutral position. Kappa values for interobserver reliability were 0.87 in the crimp grip position and 0.59 in the neutral position.MRI examination in the crimp grip position results in higher tendon bone distances by subjecting the pulleys to a higher strain, which facilitates image evaluation with higher interobserver reliability, higher sensitivity, and higher specificity for combined pulley rupture compared with examination in the neutral position.
EVALuna2:14345

Strukturelle, prozedurale und personelle Voraussetzung für die Erbringung radioonkologischer und strahlentherapeutischer Leistungen 2023 in Deutschland – ein Positionspapier der Deutschen Gesellschaft für Radioonkologie (DEGRO) - Fietkau, Rainer; Höller, Ulrike; Krause, Mechthild; Petersen, Cordula; van Kampen, Michael; Vordermark, Dirk; Willner, Jochen (Strahlentherapie und Onkologie, 2023)
CRIS-Team Scopus Importer:2023-07-07

Study of the anti-inflammatory effects of low-dose radiation: The contribution of biphasic regulation of the antioxidative system in endothelial cells - Large, Martin; Hehlgans, Stephanie; Reichert, Sebastian; Gaipl, Udo; Fournier, Claudia; Rödel, Claus; Weiss, Christian; Rödel, Franz (Strahlentherapie und Onkologie, 2015)
We examined (a) the expression of the antioxidative factor glutathione peroxidase (GPx) and the transcription factor nuclear factor E2-related factor 2 (Nrf2) following low-dose X-irradiation in endothelial cells (ECs) and (b) the impact of reactive oxygen species (ROS) and Nrf2 on functional properties of ECs to gain further knowledge about the anti-inflammatory mode of action of low doses of ionizing radiation.EA.hy926 ECs and primary human dermal microvascular ECs (HMVEC) were stimulated by tumor necrosis factor-? (TNF-?, 20 ng/ml) 4 h before irradiation with single doses ranging from 0.3 to 3 Gy. The expression and activity of GPx and Nrf2 were analyzed by flow cytometry, colorimetric assays, and real-time PCR. The impact of ROS and Nrf2 on peripheral blood mononuclear cell (PBMC) adhesion was assayed in the presence of the ROS scavenger N-acetyl-L-cysteine (NAC) and Nrf2 activator AI-1.Following a low-dose exposure, we observed in EA.hy926 EC and HMVECs a discontinuous expression and enzymatic activity of GPx concomitant with a lowered expression and DNA binding activity of Nrf2 that was most pronounced at a dose of 0.5 Gy. Scavenging of ROS by NAC and activation of Nrf2 by AI-1 significantly diminished a lowered adhesion of PBMC to EC at a dose of 0.5 Gy.Low-dose irradiation resulted in a nonlinear expression and activity of major compounds of the antioxidative system that might contribute to anti-inflammatory effects in stimulated ECs.
EVALuna2:18305

Study on the Impact of CMV-Encephalopathy on the Survival of Brain Cancer Patients Undergoing Radio(Chemo) therapy of the Brain - Goerig, Nicole; Frey, Benjamin; Korn, Klaus; Fleckenstein, Bernhard; Überla, Klaus; Schmidt, M. A.; Engelhorn, Tobias; Dörfler, Arnd; Eyüpoglu, Ilker Yasin; Merkel, Andreas; Rühle, Paul-Friedrich; Putz, F.; et al. (2017)
EVALuna2:32868

Substantial Impairment of Quality of Life during COVID-19 Pandemic in Patients with Advanced Rectal Cancer - Dennison, Irene; Schweizer, Claudia; Fitz, Tim; Blasko, Daniel; Sörgel, Christopher; Kallies, Annett; Schmidt, Linda; Fietkau, Rainer; Distel, Luitpold (Healthcare, 2022)
The aim of this study was to analyze the quality of life of patients with advanced rectal cancer before and during the COVID-19 pandemic and to determine whether the pandemic affected patients' quality of life. The study included 389 patients and was performed from May 2010 to June 2021. The fifteen months from March 2020 to June 2021 were categorized as the COVID-19 period. Patients were surveyed using the QLQ-C30 and QLQ-CR38 questionnaires. The questionnaires were used at different phases of radiochemotherapy: prior to RCT (day 1), during RCT (day 14), at the end of RCT (day 35), and prior to mesorectal surgery (day 70). Scores were formed from the questions. In addition, scores were analyzed for different age groups (64) and sexes (female and male). Overall, patients reported lower functional scores and higher symptom scores during the pandemic than before the pandemic. Although it had been expected that older and younger patients would differ clearly, there were only minor differences. The comparison between the two sexes showed very different scores, with female patients having lower functional scores and higher symptom scores than male patients before and especially during COVID-19. In conclusion, age does not play a major role in quality of life, but sex does play an important role in perception of functioning and symptoms. COVID-19 also had a major impact on patients' lives, as it was a very isolating and stressful time for everyone, especially cancer patients, which was reflected in worsening scores.
CRIS-Team WoS Importer:2022-09-09

Successful implementation of online educational lectures of the German Society for Radiation Oncology (DEGRO) - Büttner, Marcel; Melton, Philip; Fietkau, Rainer; Petersen, Cordula; Krause, Mechthild; Borgmann, Kerstin; Wolf, Ulrich; Niyazi, Maximilian; Christiansen, Hans; Höller, Ulrike; Schmitt, Daniela; Käsmann, Lukas; et al. (Strahlentherapie und Onkologie, 2023)
Purpose: Modern digital teaching formats have become increasingly important in recent years, in part due to the COVID-19 pandemic. In January 2021, an online-based webinar series was established by the German Society for Radiation Oncology (DEGRO) and the young DEGRO (yDEGRO) working group. In the monthly 120-minute courses, selected lecturers teach curricular content as preparation for the board certification exam for radiation oncology. Methods: The evaluation of the 24 courses between 01.2021 and 12.2022 was performed using a standardized questionnaire with 21 items (recording epidemiological characteristics of the participants, didactic quality, content quality). A Likert scale (1–4) was used in combination with binary and open-ended questions. Results: A combined total of 4200 individuals (1952 in 2021 and 2248 in 2022) registered for the courses, and out of those, 934 participants (455 in 2021 and 479 in 2022) later provided evaluations for the respective courses (36% residents, 35% specialists, 21% medical technicians for radiology [MTR], 8% medical physics experts [MPE]). After 2 years, 74% of the DEGRO Academy curriculum topics were covered by the monthly webinars. The overall rating by participants was positive (mean 2021: 1.33 and 2022: 1.25) and exceeded the curriculum offered at each site for 70% of participants. Case-based learning was identified as a particularly well-rated method. Conclusion: The DEGRO webinar expands the digital teaching opportunities in radiation oncology. The consistently high number of participants confirms the need for high-quality teaching and underlines the advantages of e‑learning methods. Optimization opportunities were identified through reevaluation of feedback from course participants. In its design as a teaching format for a multiprofessional audience, the webinar series could be used as a practice model of online teaching for other disciplines.
CRIS-Team Scopus Importer:2023-11-03
Keywords: e‑learning; Medical education; Online webinar; Radiation oncology; Teaching format

Successful Multidisciplinary Treatment with Secondary Metastatic Liver Resection after Downsizing by Palliative Second-Line Treatment of Colorectal Cancer: A Curative Option - Wein, Axel; Görtz, Rüdiger; Wolff, Kerstin; Ostermeier, Nicola; Busse, Daniel; Kremer, Andreas; Koch, Franz; Hagel, Alexander; Farnbacher, Michael; Kammerer, Ferdinand J.; Neurath, Markus; Grützmann, Robert; et al. (Case Reports in Oncology, 2016)
The prognostic outcome following progression after palliative first-line treatment for patients suffering from metastatic colorectal adenocarcinoma is generally poor. Long-term relapse-free survival with palliative second-line treatment may be achieved in only a limited number of individual cases.A 37-year-old patient presented with bilobar liver metastases of colon cancer confirmed by histology with wild-type K-RAS (exon 2). Due to progressive disease after eight cycles of first-line therapy with FOLFIRI plus cetuximab, second-line chemotherapy with modified FOLFOX4 (mFOLFOX4) plus bevacizumab was initiated. During four cycles of mFOLFOX4 plus bevacizumab (2 months), no higher-grade toxicity occurred. Liver MRI with contrast medium revealed downsizing of the segment II/III metastases, as well as regressive, small, faint, hardly definable lesions in segments VI and IVb. The interdisciplinary tumor board of the University of Erlangen thus decided to perform resection of the liver metastases. Segments II and III were resected, and the liver metastases in segments IVa and VI were excised (R0). Histopathology confirmed three of the R0-resected metastases to be completely necrotic, with residual scarring. As perioperative therapy, four additional cycles of mFOLFOX4 plus bevacizumab were administered postoperatively. No higher-grade toxicity was observed. Three years after the initial diagnosis, the patient is relapse free, professionally fully reintegrated, and has an excellent performance status.Patients suffering from metastatic colorectal cancer may benefit from multidisciplinary treatment with secondary metastatic liver resection after downsizing by palliative second-line treatment. In individual cases, patients may even have a curative treatment option, provided that close interdisciplinary collaboration exists.
EVALuna2:2220

Superparamagnetic iron oxide nanoparticles as novel x-ray enhancer for low-dose radiation therapy - Klein, Stefanie; Sommer, Anja; Distel, Luitpold; Hazemann, Jean-Louis; Kroener, Wolfgang; Neuhuber, Winfried; Müller, Paul; Proux, Olivier; Kryschi, Carola (Journal of Physical Chemistry B, 2014)
Superparamagnetic iron oxide nanoparticles (SPIONs) with a mixed phase composition (γ-FeO)(Fe O)and sizes between 9 and 20 nm were synthesized via coprecipitation and were either left uncoated or subsequently surface-stabilized with citrate or malate anions. The sizes, morphology, surface chemistry, and magnetic properties of the nanoparticles were characterized using transmission electron microscopy (TEM), Fourier transform infrared spectroscopy, and superconducting quantum interference device measurements, respectively. Cellular uptake and intracellular distribution in normal tissue and tumor cells were verified by TEM images. X-ray-induced changes of the oxidation state and site geometries of surface iron ions of uncoated and citrate-coated SPIONs were explored by collecting Fe K-edge X-ray absorption spectroscopy data. The potential applicability of citrate- and malate-coated SPIONs as an X-ray enhancer for radiation cancer therapy was substantiated by their drastic enhancement of the concentration of reactive oxygen species (ROS) in X-ray irradiated tumor cells. © 2014 American Chemical Society.

Superparamagnetic iron oxide nanoparticles as radiosensitizer via enhanced reactive oxygen species formation - Klein, Stefanie; Sommer, Anja; Distel, Luitpold; Neuhuber, Winfried; Kryschi, Carola (Biochemical and Biophysical Research Communications, 2012)
Internalization of citrate-coated and uncoated superparamagnetic iron oxide nanoparticles by human breast cancer (MCF-7) cells was verified by transmission electron microscopy imaging. Cytotoxicity studies employing metabolic and trypan blue assays manifested their excellent biocompatibility. The production of reactive oxygen species in iron oxide nanoparticle loaded MCF-7 cells was explained to originate from both, the release of iron ions and their catalytically active surfaces. Both initiate the Fenton and Haber-Weiss reaction. Additional oxidative stress caused by X-ray irradiation of MCF-7 cells was attributed to the increase of catalytically active iron oxide nanoparticle surfaces. © 2012 Elsevier Inc.

Supervised Contrastive Learning for Robust and Efficient Multi-modal Emotion and Sentiment Analysis - Gomaa, Ahmed; Maier, Andreas; Kosti, Ronak Vijaypal (2022 26TH INTERNATIONAL CONFERENCE ON PATTERN RECOGNITION (ICPR), 2022)
CRIS-Team WoS Importer:2023-02-17

Support vector machine-based prediction of local tumor control after stereotactic body radiation therapy for early-stage non-small cell lung cancer - Klement, Rainer J.; Allgaeuer, Michael; Appold, Steffen; Dieckmann, Karin; Ernst, Iris; Ganswindt, Ute; Holy, Richard; Nestle, Ursula; Nevinny-Stickel, Meinhard; Semrau, Sabine; Sterzing, Florian; Wittig, Andrea; et al. (International Journal of Radiation Oncology Biology Physics, 2014)
Several prognostic factors for local tumor control probability (TCP) after stereotactic body radiation therapy (SBRT) for early stage non-small cell lung cancer (NSCLC) have been described, but no attempts have been undertaken to explore whether a nonlinear combination of potential factors might synergistically improve the prediction of local control.We investigated a support vector machine (SVM) for predicting TCP in a cohort of 399 patients treated at 13 German and Austrian institutions. Among 7 potential input features for the SVM we selected those most important on the basis of forward feature selection, thereby evaluating classifier performance by using 10-fold cross-validation and computing the area under the ROC curve (AUC). The final SVM classifier was built by repeating the feature selection 10 times with different splitting of the data for cross-validation and finally choosing only those features that were selected at least 5 out of 10 times. It was compared with a multivariate logistic model that was built by forward feature selection.Local failure occurred in 12% of patients. Biologically effective dose (BED) at the isocenter (BED(ISO)) was the strongest predictor of TCP in the logistic model and also the most frequently selected input feature for the SVM. A bivariate logistic function of BED(ISO) and the pulmonary function indicator forced expiratory volume in 1 second (FEV1) yielded the best description of the data but resulted in a significantly smaller AUC than the final SVM classifier with the input features BED(ISO), age, baseline Karnofsky index, and FEV1 (0.696 ± 0.040 vs 0.789 ± 0.001, P<.03). The final SVM resulted in sensitivity and specificity of 67.0% ± 0.5% and 78.7% ± 0.3%, respectively.These results confirm that machine learning techniques like SVMs can be successfully applied to predict treatment outcome after SBRT. Improvements over traditional TCP modeling are expected through a nonlinear combination of multiple features, eventually helping in the task of personalized treatment planning.
EVALuna2:18195

Suppression of proatherogenic leukocyte interactions by MCS-18 - Impact on advanced atherosclerosis in ApoE-deficient mice - Kühn, Constanze; Tauchi, Miyuki; Stumpf, Christian; Daniel, Christoph; Bäuerle, Tobias; Schwarz, Marc; Kerek, Franz; Steinkasserer, Alexander; Zinser, Elisabeth; Achenbach, Stephan; Dietel, Barbara (Atherosclerosis, 2016)
Atherosclerosis is associated with chronic inflammatory responses of the arterial blood vessels. The previously observed protective effect of the MCS-18 substance against the initiation of atherosclerosis in a murine model was explained by its pronounced anti-inflammatory activity. Here, we investigated its impact on murine plaque progression in advanced atherosclerosis and on proatherogenic processes.ApoE-deficient mice were fed a high-fat diet for 12 weeks to induce atherosclerosis, followed by normal chow and intraperitoneal injections of either MCS-18 (500 ?g, n = 10) or saline (n = 10) twice a week for another 12 weeks. Plaque size was reduced in MCS-18 treated mice compared to controls (p = 0.001), which was associated with a reduced size of the lipid core (p = 0.01). There was a decrease in apoptotic cells (p = 0.02), endothelial ICAM-1 expression (p < 0.001), and macrophage density (p = 0.01) in the MCS-18 group. In addition, human and murine dendritic cells (DCs) and human umbilical vein endothelial cells (HUVECs) were treated with MCS-18 (50-200 ?g/ml) to analyze cell migration and adhesion under flow conditions. MCS-18 reduced human (p = 0.01) and murine (p = 0.006) DC migration. Furthermore, adhesion of MCS-18-treated DCs to a HUVEC monolayer was decreased (p < 0.001). Compared to controls, CD209 (p < 0.001) and CCR7 (p = 0.003) expression was decreased in MCS-18-treated DCs, while in HUVECs lower levels of ICAM-1 (p < 0.001) and of phosphorylated NF-?B-p65 (p = 0.002) were observed. Blocking of ICAM-1 reduced DC adhesion (p < 0.001).MCS-18 exhibits interesting therapeutic effects when applied in advanced murine atherosclerosis. Its antiatherogenic impact might be associated with a suppressed adhesion to the endothelium due to down-regulation of endothelial ICAM-1 expression.
EVALuna2:12031

Surgical hematoma evacuation of cortical intracerebral hemorrhage ≥10 ml reduces risk of subsequent epilepsy by more than 70%: A retrospective monocenter study - Welte, Tamara; Steidl, Josephine; Stritzelberger, Jenny; Gollwitzer, Stephanie; Lang, Johannes; Reindl, Caroline; Rampp, Stefan; Maslarova, Anna; Brandner, Sebastian; Hock, Stefan; Mühlen, Iris; Dörfler, Arnd; et al. (European Journal of Neurology, 2022)
Aim: The aim of this study was to re-evaluate risk factors for post-ICH epilepsy (PICHE) and examine the impact of surgical hematoma evacuation on epilepsy development after ICH. Background and purpose: Epilepsy is a common complication after intracerebral hemorrhage (ICH). Information on risk factors is still scarce and the role of ICH evacuation remains uncertain. Methods: We retrospectively included patients with spontaneous ICH treated in our hospital in 2006–2019. Patients' medical records were analyzed. In addition, mailed questionnaires and telephone interviews were used to complete the dataset. Uni- and multivariable hazard ratios (HRs) were applied to investigate risk factors for PICHE and the impact of surgical ICH evacuation. Results: Among 587 ICH patients available for analyses, 139 (23.7%) developed PICHE (mean follow-up 1795 ± 1378 days). The median time of epilepsy onset was 7 months after ICH (range 1–132 months). Risk factors associated with PICHE were cortical hemorrhage (multivariable HR 1.65 [95% CI 1.14–2.37]; p = 0.008), ICH volume > 10 ml (multivariable HR 1.91 [95% CI 1.33–2.73]; p < 0.001) and acute symptomatic seizures (multivariable HR 1.81 [95% CI 1.20–2.75]; p = 0.005). Patients with cortical ICH > 10 ml who underwent surgical hematoma evacuation were less likely to develop epilepsy than those with conservative treatment alone (multivariable HR 0.26 [95% CI 0.08–0.84]; p = 0.025). Conclusions: Post-ICH epilepsy is frequent and predicted by large cortical ICH and acute symptomatic seizures. Hematoma evacuation reduced the risk of PICHE by more than 70% in patients with large cortical ICH. This finding could be considered in the clinical decision making on the acute treatment of ICH.
CRIS-Team Scopus Importer:2022-10-21
Keywords: CAVE score; hematoma evacuation; intracerebral hemorrhage; post-stroke epilepsy

Survey on brachytherapy training among radiation oncology residents in the German-speaking regions of Europe - Knoth, Johannes; Konrad, Stefan; Lössl, Kristina; Motisi, Laura; Mäurer, Matthias; Linde, Philipp; Lindel, Katja; Niehoff, Peter; Strnad, Vratislav; Sturdza, Alina; Corradini, Stefanie (Strahlentherapie und Onkologie, 2023)
Purpose: This survey aimed to determine the perception of brachytherapy training among residents in the DACH region, consisting of Austria, Germany and Switzerland. Material & Methods: An online questionnaire containing 22 questions related to trainee demographics (n = 5) and to brachytherapy training (n = 17) was sent in two iterations in 11/2019 and 02/2020. The following topics were evaluated: institutional support, barriers to training, extent of training, site-specific training (prostate, gynaecology, breast, gastrointestinal and skin), preferences for further training and outlook on overall development of brachytherapy. The responses were mostly based on a Likert scale of 1 to 5, thereby reflecting strength of opinion. Descriptive statistics were used to describe frequencies. Results: Among the 108 respondents, approximately 69% of residents considered the ability to perform brachytherapy independently to be important or somewhat important. However, only 31% of respondents reported to have a dedicated brachytherapy training during residency. The major limitation to achieve independence in performing brachytherapy was seen in a low case load in Austria, in the lack of training in Switzerland and in both of them in Germany. Conclusion: The interest in brachytherapy training among residents in German-speaking countries was generally high, but there is a perceived lack of sufficient case volumes and partially also in formal training opportunities. Fellowships at departments with a high case load as part of a formalised curriculum and dedicated hands-on workshops at national or international conferences might help to overcome these issues.
CRIS-Team Scopus Importer:2023-07-28
Keywords: Career choice; Education; Questionnaire; Survey; Teaching

Survey within the German Society for Radiation Oncology (DEGRO) on the Diagnosis and Treatment of Salivary Gland Carcinomas - Von Der Gruen, J.; Roedel, C.; Balermpas, P.; Martin, D.; Semrau, Sabine; Fietkau, Rainer; Haderlein, Marlen (STRAHLENTHERAPIE UND ONKOLOGIE, 2021)
CRIS-Team WoS Importer:2021-07-16

Survival analysis in rectal carcinoma after neoadjuvant chemoradiation: various methods with different results - Merkel, Susanne; Weber, Klaus; Göhl, Jonas; Agaimy, Abbas; Fietkau, Rainer; Hohenberger, Werner; Grützmann, Robert; Hermanek, Peter (International Journal of Colorectal Disease, 2017)
Survival is an important indicator of outcome quality in rectal carcinoma. The 5-year survival rate is the typical outcome measurement. In patients with neoadjuvant chemoradiation followed by curative surgery, 7 years of follow-up is recommended. Different methods of survival analysis lead to different results. Here, we compared four different methods.The data of 439 patients with rectal carcinoma treated with neoadjuvant chemoradiation followed by curative total mesorectal excision (TME) surgery between 1995 and 2010 were analysed. After stratifying by stage, relative survival (RS), cancer-related survival (CRS), overall survival (OS) and disease-free survival (DFS) were compared. In particular, the 3-year disease-free survival rate was compared to the 5- and 7-year overall survival rates.In the total cohort, the 5-year survival rates ranged from 90% (RS), over 84% (CRS) and 83% (OS) to 72% (DFS). Depending on the stage of disease, the differences between the 5-year survival rates varied between 10 and 32 percentage points. The differences were lowest in UICC stage y0 and highest in UICC stage yIV. The 3-year DFS-rate was always lower (worse) than the 5-year OS rate and higher (better) than the 7-year OS rate, with the exception of stage yIV.Comparisons of survival are only meaningful if the same methods are applied. The 3-year rate of DFS was always worse than the rate of 5-year OS. Therefore, the 3-year rate of DFS appears to be a useful surrogate indicator in rectal carcinoma treatment studies.
EVALuna2:6896

Synthetic CTs for MRI-only brain RT treatment: integration of immobilization systems - Masitho, Siti; Grigo, Johanna; Brandt, Tobias; Lambrecht, Ulrike; Szkitsak, Juliane; Weiß, Alexander; Fietkau, Rainer; Putz, Florian; Bert, Christoph (Strahlentherapie und Onkologie, 2023)
Purpose: Auxiliary devices such as immobilization systems should be considered in synthetic CT (sCT)-based treatment planning (TP) for MRI-only brain radiotherapy (RT). A method for auxiliary device definition in the sCT is introduced, and its dosimetric impact on the sCT-based TP is addressed. Methods: T1-VIBE DIXON was acquired in an RT setup. Ten datasets were retrospectively used for sCT generation. Silicone markers were used to determine the auxiliary devices’ relative position. An auxiliary structure template (AST) was created in the TP system and placed manually on the MRI. Various RT mask characteristics were simulated in the sCT and investigated by recalculating the CT-based clinical plan on the sCT. The influence of auxiliary devices was investigated by creating static fields aimed at artificial planning target volumes (PTVs) in the CT and recalculated in the sCT. The dose covering 50% of the PTV (D50) deviation percentage between CT-based/recalculated plan (∆D50[%]) was evaluated. Results: Defining an optimal RT mask yielded a ∆D50[%] of 0.2 ± 1.03% for the PTV and between −1.6 ± 3.4% and 1.1 ± 2.0% for OARs. Evaluating each static field, the largest ∆D50[%] was delivered by AST positioning inaccuracy (max: 3.5 ± 2.4%), followed by the RT table (max: 3.6 ± 1.2%) and the RT mask (max: 3.0 ± 0.8% [anterior], 1.6 ± 0.4% [rest]). No correlation between ∆D50[%] and beam depth was found for the sum of opposing beams, except for (45° + 315°). Conclusion: This study evaluated the integration of auxiliary devices and their dosimetric influence on sCT-based TP. The AST can be easily integrated into the sCT-based TP. Further, we found that the dosimetric impact was within an acceptable range for an MRI-only workflow.
CRIS-Team Scopus Importer:2023-07-21
Keywords: Artificial intelligence; Image-guided radiotherapy; Radiotherapy setup; Stereotactic radiosurgery; Treatment planning

Systemic effects of radiotherapy: immune mechanisms, pre-clinical data and clinical evidence - Gaipl, Udo (2018)
EVALuna2:36522

Systemic modulation of stress and immune parameters in patients treated for prostate adenocarcinoma by intensity-modulated radiation therapy or stereotactic ablative body radiotherapy - Frey, Benjamin; Mika, J.; Jelonek, K.; Cruz-Garcia, L.; Roelants, C.; Testard, I.; Cherradi, N.; Lumniczky, K.; Polozov, S.; Napieralska, A.; Widlak, P.; Gaipl, Udo; et al. (Strahlentherapie und Onkologie, 2020)
Background: In this exploratory study, the impact of local irradiation on systemic changes in stress and immune parameters was investigated in eight patients treated with intensity-modulated radiation therapy (IMRT) or stereotactic ablative body radiotherapy (SABR) for prostate adenocarcinoma to gain deeper insights into how radiotherapy (RT) modulates the immune system. Patients and methods: RT-qPCR, flow cytometry, metabolomics, and antibody arrays were used to monitor a panel of stress- and immune-related parameters before RT, after the first fraction (SABR) or the first week of treatment (IMRT), after the last fraction, and 3 weeks later in the blood of IMRT (N = 4) or SABR (N = 4) patients. Effect size analysis was used for comparison of results at different timepoints. Results: Several parameters were found to be differentially modulated in IMRT and SABR patients: the expression of TGFB1, IL1B, and CCL3 genes; the expression of HLA-DR on circulating monocytes; the abundance and ratio of phosphatidylcholine and lysophosphatidylcholine metabolites in plasma. More immune modulators in plasma were modulated during IMRT than SABR, with only two common proteins, namely GDF-15 and Tim‑3. Conclusion: Locally delivered RT induces systemic modulation of the immune system in prostate adenocarcinoma patients. IMRT and SABR appear to specifically affect distinct immune components.
CRIS-Team Scopus Importer:2020-06-16
Keywords: Biomarkers of radiation exposure; Immunophenotyping; Ionizing radiation; Prostate cancer; Systemic immune modulation

T1-SPACE vs. T1-MPRAGE for Target Volume Definition in Brain Metastases - a radiotherapy-oriented Comparison - Mansoorian, S.; Mengling, Veit; Masitho, Siti; Perrin, R.; Siavooshaghighi, H.; Weissmann, T.; Filimonova, Irina; Bert, Christoph; Fietkau, Rainer; Putz, Florian (STRAHLENTHERAPIE UND ONKOLOGIE, 2020)
CRIS-Team WoS Importer:2020-10-02

Targeted Natural Killer Cell-Based Adoptive Immunotherapy for the Treatment of Patients with NSCLC after Radiochemotherapy: A Randomized Phase II Clinical Trial - Multhoff, Gabriele; Seier, Sophie; Stangl, Stefan; Sievert, Wolfgang; Shevtsov, Maxim; Werner, Caroline; Pockley, A. Graham; Blankenstein, Christiane; Hildebrandt, Martin; Offner, Robert; Ahrens, Norbert; Kokowski, Konrad; et al. (Clinical Cancer Research, 2020)
Purpose: Non-small cell lung cancer (NSCLC) is a fatal disease with poor prognosis. Amembrane-bound form of Hsp70 (mHsp70) which is selectively expressed on high-risk tumors serves as a target for mHsp70-targeting natural killer (NK) cells. Patients with advanced mHsp70-positive NSCLC may therefore benefit from a therapeutic intervention involving mHsp70-targeting NK cells. The randomized phase II clinical trial (EudraCT2008-002130-30) explores tolerability and efficacy of ex vivo-activated NK cells in patients with NSCLC after radiochemotherapy (RCT).
CRIS-Team WoS Importer:2020-11-13

Targeted Natural Killer (NK) cell based adoptive immunotherapy for the treatment of patients with non-small cell lung cancer (NSCLC) after radiochemotherapy results of a randomized phase II clinical trial (NSCLC-TKD/IL-2) (Eudra-CT Number 2008-002130-30) - Multhoff, Gabriele; Combs, Stephanie E.; Seier, Sophie; Stangl, Stefan; Sievert, Wolfgang; Shevtsov, Maxim; Blankenstein, Christiane; Hildebrandt, Martin; Kokowski, Konrad; Hautmann, Matthias; Hautmann, Hubert; Roedel, Claus; et al. (CANCER RESEARCH, 2020)
CRIS-Team WoS Importer:2021-03-05

Targeted next-generation sequencing identifies molecular subgroups in squamous cell carcinoma of the head and neck with distinct outcome after concurrent chemoradiation - Tinhofer, I.; Stenzinger, A.; Eder, T.; Konschak, R.; Niehr, F.; Endris, V.; Distel, Luitpold; Hautmann, M. G.; Mandic, R.; Stromberger, C.; Weichert, W.; Budach, V. (Annals of Oncology, 2016)
BACKGROUND: Based on epidemiological (HPV status, smoking habits) and clinical risk factors (T/N stage), three subgroups of patients suffering from locally advanced oropharyngeal carcinoma with significantly different outcome after concurrent chemoradiation (cCRTX) can be distinguished. Mutational profiling by targeted next-generation sequencing (NGS) might further improve risk stratification. PATIENTS AND METHODS: Patients with stage IV squamous cell carcinoma of the oropharynx and hypopharynx who had been enrolled in a randomized phase III trial (ARO-0401) comparing two regimens of cCRTX and from whom archival tumor specimens were available were included. The HPV status was determined by p16 immunostaining and detection of HPV DNA. Targeted NGS covering 45 genes frequently altered in squamous cell carcinoma of the head and neck (SCCHN) was applied for detection of non-synonymous somatic and germline mutations. Interference of mutational profiles with cCRTX efficacy was determined. RESULTS: The prognostic value of the 'Ang' risk model could be confirmed in the total biomarker study cohort (N = 175) as well as the patient subgroup for which mutational profiles could be established (N = 97). Mutations in genes involved in phosphoinositide 3-kinase (PI3K), receptor tyrosine kinase (RTK), and p53 signaling pathways were significantly enriched in the low- (N = 7), intermediate- (N = 20), and high-risk group (N = 70), respectively. Mutations in TP53 identified a subgroup of high-risk patients with dismal outcome after cCRTX. No prognostic relevance was observed for mutations in PI3K and RTK signaling pathways in the low- and intermediate-risk groups, respectively. Mutated NOTCH1 and two functional KDR germline variants (rs2305948, rs1870377) were associated with improved outcome in all risk groups. All genetic markers (TP53, NOTCH1, KDR) remained independent prognosticators of OS in the multivariate model. CONCLUSION: A potential of targeted NGS for risk classification of SCCHN cases beyond HPV status and clinical factors was demonstrated.
EVALuna2:33046

Targeted Therapy, Chemotherapy, Immunotherapy and Novel Treatment Options for Different Subtypes of Salivary Gland Cancer - Mueller, Sarina K.; Haderlein, Marlen; Lettmaier, Sebastian; Agaimy, Abbas; Haller, Florian; Hecht, Markus; Fietkau, Rainer; Iro, Heinrich; Mantsopoulos, Konstantinos (Journal of Clinical Medicine, 2022)
Surgical resection remains the first line treatment for salivary gland cancer (SGC). In the case of locally advanced disease, surgery is followed by adjuvant radiotherapy. Surgical resection should be favored in resectable locoregional recurrent disease as well, and even the complete resection of all distant oligometastases has clinical benefit for the patients. For inoperable and disseminated metastatic disease, a multitude of systemic therapies including chemotherapy, targeted therapy, and immunotherapy are available. In this review, the current therapeutic options for inoperable recurrent or metastatic SGCs are summarized. Systemic treatment can achieve prolonged progression-free and overall survival, while the overall prognosis remains poor. Current clinical trials include only a limited number of patients and mostly combine different histologic subtypes. Additionally, no randomized controlled trial comparing different therapeutic options has been performed. In the future, further studies with a larger patient cohort and ideally only one histologic subtype are needed in order to improve the outcome for SGC patients. However, this may be difficult to accomplish due to the rarity and diversity of the disease. Additionally, molecular analyses need to be performed routinely in order to individualize treatment and to go one step further towards precision medicine.
CRIS-Team Scopus Importer:2022-02-04
Keywords: Acinic cell carcinoma; Adenoid cystic carcinoma; Chemotherapy; Immunotherapy; Mucoepidermoid carcinoma; Salivary duct carcinoma; Salivary gland cancer; Targeted therapy

Targeting of drug-loaded nanoparticles to tumor sites increases cell death and release of danger signals - Alev, Magdalena; Egenberger, Laura; Mühleisen, Laura; Weigel, Bianca; Frey, Benjamin; Friedrich, Ralf P.; Poettler, Marina; Alexiou, Christoph; Janko, Christina (Journal of Controlled Release, 2018)
Innovative strategies fighting cancer by inducing anti-tumor responses from the immune system are urgently needed. Amongst others, chemotherapeutics from the class of the anthracyclines have been shown to induce death of cancer cells with immunogenic features and triggering immunogenic anti-tumor responses. However, the patient's immune system often becomes severely impaired by the unspecific action of these cytotoxic drugs in systemic chemotherapy, preventing any effective immune reactions. To reduce systemic side effects and to accumulate the drug exclusively in the tumor region, we developed an iron oxide nanoparticle-based system for the magnetically targeted delivery of mitoxantrone to the tumor, which has previously proven its long-term therapeutic efficacy in tumor bearing rabbits. Here, we show in vitro that superparamagnetic iron oxide nanoparticles (SPIONs), loaded with the chemotherapeutic drug mitoxantrone, are able to induce cell death with immunogenic features and concomitant maturation of dendritic cells, comparable to the free drug, whereas unloaded nanoparticles are very biocompatible. We conclude that the targeted delivery of mitoxantrone to the tumor region might be a promising possibility to selectively modulate the tumor microenvironment and to locally stimulate immune responses against the tumor. Thus, SPIONs can be used as a platform to specifically bring immunogenic cell death inducers (e.g. mitoxantrone, hypericin, doxorubicin) to the tumor region by sparing the immune system from their toxic effects.
EVALuna2:35474

Targeting zonulin and intestinal epithelial barrier function to prevent onset of arthritis - Tajik, Narges; Frech, Michael; Schulz, Oscar; Schälter, Fabian; Lucas, Sébastien; Azizov, Vugar; Dürholz, Kerstin; Steffen, Franziska; Omata, Yasunori; Rings, Andreas; Bertog, Marko; Rizzo, Aroldo; et al. (Nature Communications, 2020)
Gut microbial dysbiosis is associated with the development of autoimmune disease, but the mechanisms by which microbial dysbiosis affects the transition from asymptomatic autoimmunity to inflammatory disease are incompletely characterized. Here, we identify intestinal barrier integrity as an important checkpoint in translating autoimmunity to inflammation. Zonulin family peptide (zonulin), a potent regulator for intestinal tight junctions, is highly expressed in autoimmune mice and humans and can be used to predict transition from autoimmunity to inflammatory arthritis. Increased serum zonulin levels are accompanied by a leaky intestinal barrier, dysbiosis and inflammation. Restoration of the intestinal barrier in the pre-phase of arthritis using butyrate or a cannabinoid type 1 receptor agonist inhibits the development of arthritis. Moreover, treatment with the zonulin antagonist larazotide acetate, which specifically increases intestinal barrier integrity, effectively reduces arthritis onset. These data identify a preventive approach for the onset of autoimmune disease by specifically targeting impaired intestinal barrier function.
CRIS-Team Scopus Importer:2020-05-05

TARGIT-IORT During Lumpectomy for Breast Cancer Reply - Polgar, Csaba; Strnad, Vratislav; Hannoun-Levi, Jean-Michel; Major, Tibor; Takacsi-Nagy, Zoltan; Fodor, Janos (International Journal of Radiation Oncology Biology Physics, 2021)
CRIS-Team WoS Importer:2021-06-25

TCCIA: a comprehensive resource for exploring CircRNA in cancer immunotherapy - Wang, Shixiang; Xiong, Yi; Zhang, Yihao; Wang, Haitao; Chen, Minjun; Li, Jianfeng; Luo, Peng; Luo, Yung Hung; Hecht, Markus; Frey, Benjamin; Gaipl, Udo; Li, Xuejun; et al. (Journal for ImmunoTherapy of Cancer, 2024)
BACKGROUND: Immunotherapies targeting immune checkpoints have gained increasing attention in cancer treatment, emphasizing the need for predictive biomarkers. Circular RNAs (circRNAs) have emerged as critical regulators of tumor immunity, particularly in the PD-1/PD-L1 pathway, and have shown potential in predicting immunotherapy efficacy. Yet, the detailed roles of circRNAs in cancer immunotherapy are not fully understood. While existing databases focus on either circRNA profiles or immunotherapy cohorts, there is currently no platform that enables the exploration of the intricate interplay between circRNAs and anti-tumor immunotherapy. A comprehensive resource combining circRNA profiles, immunotherapy responses, and clinical outcomes is essential to advance our understanding of circRNA-mediated tumor-immune interactions and to develop effective biomarkers. METHODS: To address these gaps, we constructed The Cancer CircRNA Immunome Atlas (TCCIA), the first database that combines circRNA profiles, immunotherapy response data, and clinical outcomes across multicancer types. The construction of TCCIA involved applying standardized preprocessing to the raw sequencing FASTQ files, characterizing circRNA profiles using an ensemble approach based on four established circRNA detection tools, analyzing tumor immunophenotypes, and compiling immunotherapy response data from diverse cohorts treated with immune checkpoint blockades (ICBs). RESULTS: TCCIA encompasses over 4,000 clinical samples obtained from 25 cohorts treated with ICBs along with other treatment modalities. The database provides researchers and clinicians with a cloud-based platform that enables interactive exploration of circRNA data in the context of ICB. The platform offers a range of analytical tools, including browse of identified circRNAs, visualization of circRNA abundance and correlation, association analysis between circRNAs and clinical variables, assessment of the tumor immune microenvironment, exploration of tumor molecular signatures, evaluation of treatment response or prognosis, and identification of altered circRNAs in immunotherapy-sensitive and resistant tumors. To illustrate the utility of TCCIA, we showcase two examples, including circTMTC3 and circMGA, by employing analysis of large-scale melanoma and bladder cancer cohorts, which unveil distinct impacts and clinical implications of different circRNA expression in cancer immunotherapy. CONCLUSIONS: TCCIA represents a significant advancement over existing resources, providing a comprehensive platform to investigate the role of circRNAs in immuno-oncology.
CRIS-Team Scopus Importer:2024-01-26
Keywords: biomarkers; tumor; genetic markers; immunotherapy; tumor biomarkers

Technical evaluation of the cone-beam computed tomography imaging performance of a novel, mobile, gantry-based X-ray system for brachytherapy - Karius, Andre; Karolczak, Marek; Strnad, Vratislav; Bert, Christoph (Journal of Applied Clinical Medical Physics, 2021)
Purpose A novel, mobile cone-beam computed tomography (CBCT) system for image-guided adaptive brachytherapy was recently deployed at our hospital as worldwide first site. Prior to the device's clinical operation, a profound characterization of its imaging performance was conducted. This was essential to optimize both the imaging workflow and image quality for achieving the best possible clinical outcomes. We present the results of our investigations. Methods The novel CBCT-system features a ring gantry with 121 cm clearance as well as a 43.2 x 43.2 cm(2) flat-panel detector, and is controlled via a tablet-personal computer (PC). For evaluating its imaging performance, the geometric reproducibility as well as imaging fidelity, computed tomography (CT)-number accuracy, uniformity, contrast-noise-ratio (CNR), noise characteristics, and spatial resolution as fundamental image quality parameters were assessed. As dose metric the weighted cone-beam dose index (CBDIw) was measured. Image quality was evaluated using standard quality assurance (QA) as well as anthropomorphic upper torso and breast phantoms. Both in-house and manufacturer protocols for abdomen, pelvis, and breast imaging were examined. Results Using the in-house protocols, the QA phantom scans showed altogether a high image quality, with high CT-number accuracy (R-2 > 0.97) and uniformity (<12 Hounsfield Unit (HU) cupping), reasonable noise and imaging fidelity, and good CNR at bone-tissue transitions of up to 28:1. Spatial resolution was strongly limited by geometric instabilities of the device. The breast phantom scans fulfilled clinical requirements, whereas the abdomen and pelvis scans showed severe artifacts, particularly at air/bone-tissue transitions. Conclusion With the novel CBCT-system, achieving a high image quality appears possible in principle. However, adaptations of the standard protocols, performance enhancements in image reconstruction referring to artifact reductions, as well as the extinction of geometric instabilities are imperative.
CRIS-Team WoS Importer:2021-12-24

Technical Note: A comparison of point set registration methods for electromagnetic tracking - Götz, T. I.; Wankerl, H.; Tomé, A. M.; Meyer-Baese, A.; Bert, Christoph; Hensel, Bernhard; Lang, E. W. (Medical Physics, 2019)
Purpose: High dose rate brachytherapy applies intense and destructive radiation. A treatment plan defines radiation source dwell positions to avoid irradiating healthy tissue. The study discusses methods to quantify any positional changes of source locations along the various treatment sessions. Methods: Electromagnetic tracking (EMT) localizes the radiation source during the treatment sessions. But in each session the relative position of the patient relative to the filed generator is changed. Hence, the measured dwell point sets need to be registered onto each other to render them comparable. Two point set registration techniques are compared: a probabilistic method called coherent point drift (CPD) and a multidimensional scaling (MDS) technique. Results: Both enable using EMT without external registration and achieve very similar results with respect to dwell position determination of the radiation source. Still MDS achieves smaller grand average deviations (CPD-rPSR: MD = 2.55 mm, MDS-PSR: MD = 2.15 mm) between subsequent dwell position determinations, which also show less variance (CPD-rPSR: IQR = 4 mm, MDS-PSR: IQR = 3 mm). Furthermore, MDS is not based on approximations and does not need an iterative procedure to track sensor positions inside the implanted catheters. Conclusion: Although both methods achieve similar results, MDS is to be preferred over rigid CPD while nonrigid CPD is unsuitable as it does not preserve topology.
CRIS-Team Scopus Importer:2019-05-17
Keywords: brachytherapy; electromagnetic tracking; multi-dimensional scaling; point set registration