12/15-lipoxygenase orchestrates the clearance of apoptotic cells and maintains immunologic tolerance. - Uderhardt, Stefan; Herrmann, Martin; Oskolkova, Olga V.; Aschermann, Susanne; Bicker, Wolfgang; Ipseiz, Natacha; Sarter-Zaiss, Kerstin; Frey, Benjamin; Rothe, Tobias; Voll, Reinhard; Nimmerjahn, Falk; Bochkov, Valery N.; et al. (Immunity, 2012)
Noninflammatory clearance of apoptotic cells (ACs) is crucial to maintain self-tolerance. Here, we have reported a role for the enzyme 12/15-lipoxygenase (12/15-LO) as a central factor governing the sorting of ACs into differentially activated monocyte subpopulations. During inflammation, uptake of ACs was confined to a population of 12/15-LO-expressing, alternatively activated resident macrophages (resMΦ), which blocked uptake of ACs into freshly recruited inflammatory Ly6C(hi) monocytes in a 12/15-LO-dependent manner. ResMΦ exposed 12/15-LO-derived oxidation products of phosphatidylethanolamine (oxPE) on their plasma membranes and thereby generated a sink for distinct soluble receptors for ACs such as milk fat globule-EGF factor 8, which were essential for the uptake of ACs into inflammatory monocytes. Loss of 12/15-LO activity, in turn, resulted in an aberrant phagocytosis of ACs by inflammatory monocytes, subsequent antigen presentation of AC-derived antigens, and a lupus-like autoimmune disease. Our data reveal an unexpected key role for enzymatic lipid oxidation during the maintenance of self-tolerance.

12 x 6 Gy stereotactic radiotherapy for lung tumors. Is there a difference in response between lung metastases and primary bronchial carcinoma? - Lubgan, Dorota; Semrau, Sabine; Lambrecht, Ulrike; Gaipl, Udo; Fietkau, Rainer (Strahlentherapie und Onkologie, 2021)
Purpose The aim of this study was to evaluate the safety and long-term tumor control after stereotactic radiotherapy (SRT) with 12 x 6 Gy of patients with primary bronchial carcinoma (BC) or with pulmonary metastases (MET) of various solid tumors. Local progression-free survival (LPFS), progression-free survival (PFS), overall survival (OS), and prognostic factors were compared. Methods Between May 2012 and January 2020, 168 patients with 206 pulmonary lesions (170 MET and 36 primary BC) were treated with 12 x 6 Gy (BED10 116 Gy). The irradiated pulmonary MET were from the following cancers: 47 (27.6%) head and neck, 37 (21.8%) rectum or colon, 30 (17.6%) bronchial, 13 (7.6%) malignant melanoma, 9 (5.3%) esophageal, 9 (5.3%) sarcoma, and 25 (14.8%) other. Results The median follow-up was 16.26 months (range: 0.46-89.34) for BC and 19.18 months (0.89-91.11) for MET. Survival rates at 3 years were: OS 43% for BC and 35% for MET; LPFS BC 96% and MET 85%; PFS BC 35% and MET 29%. The most frequently observed grade 3 adverse events (AEs) were pneumonitis (5.9% BC, 4.8% MET), pulmonary fibrosis (2.9% BC, 4% MET), and pulmonary embolism (2.9% BC, 0.8% MET). The favorable prognostic effects on overall survival of patients with MET were female gender (log-rank: p < 0.001), no systemic progression (log-rank; p = 0.048, multivariate COX regression p = 0.039), and malignant melanoma histology (log-rank; p = 0.015, multivariate COX regression p = 0.020). For patients with BC, it was tumor location within the lower lobe (vs. upper lobe, log-rank p = 0.027). LPFS of patients with metastatic disease was beneficially influenced by female gender (log-rank: p = 0.049). Conclusion The treatment concept of 12 x 6 Gy is associated with 96% local progression-free survival for BC and 85% for pulmonary metastases after 3 years. There was no difference in response after SRT of primary lung carcinoma or pulmonary metastases.
CRIS-Team WoS Importer:2021-07-30

12 x 6 Gy stereotactic radiotherapy for lung tumours. Is there a difference in response between lung metastases and primary bronchial carcinoma? - Lubgan, Dorota; Semrau, Sabine; Lambrecht, U.; Gaipl, Udo; Fietkau, Rainer (STRAHLENTHERAPIE UND ONKOLOGIE, 2021)
CRIS-Team WoS Importer:2021-07-16

12x6Gy-the Erlangen stereotactic radiotherapy treatment concept result in 95% local progression-free survival for bronchial carcinoma and 83% for pulmonary metastases after 3 years - Lubgan, Dorota; Rutzner, Sandra; Lambrecht, U.; Fietkau, Rainer (2018)
EVALuna2:36517

3D convolutional neural network-based autosegmentation improves brain metastases detection and quantification for brain stereotactic radiotherapy treatment planning - Putz, Florian; Weissmann, Thomas; Mansoorian, Sina; Schmidt, Manuel; Heiß, Rafael; Semrau, Sabine; Frey, Benjamin; Bert, Christoph; Fietkau, Rainer (STRAHLENTHERAPIE UND ONKOLOGIE, 2021)
CRIS-Team WoS Importer:2021-07-16

3D-Shaped Binders of Unfolded Proteins Inducing Cancer Cell-Specific Endoplasmic Reticulum Stress In Vitro and In Vivo - Klemt, Insa; Varzatskii, Oleg; Selin, Roman; Vakarov, Serhii; Kovalska, Vladyslava B.; Bila, Galyna; Bilyy, Rostyslav; Voloshin, Yan; Cossío Cuartero, Itziar; Hidalgo, Andrés; Frey, Benjamin; Becker, Ina; et al. (Journal of the American Chemical Society, 2023)
The amount of unfolded proteins is increased in cancer cells, leading to endoplasmic reticulum (ER) stress. Therefore, cancer cells are sensitive to drugs capable of further enhancing ER stress. Examples of such drugs include the clinically approved proteosome inhibitors bortezomib and carfilzomib. Unfortunately, the known ER stress inducers exhibit dose-limiting side effects that justify the search for better, more cancer-specific drugs of this type. Herein, we report on FeC 2, which binds to unfolded proteins prevents their further processing, thereby leading to ER stress and ROS increase in cancer cells, but not in normal cells. FeC 2 exhibits low micromolar toxicity toward human acute promyelocytic leukemia HL-60, Burkitt’s lymphoma BL-2, T-cell leukemia Jurkat, ovarian carcinoma A2780, lung cancer SK-MES-1, and murine lung cancer LLC1 cells. Due to the cancer-specific mode of action, 2 is not toxic in vivo up to the dose of 147 mg/kg, does not affect normal blood and bone marrow cells at the therapeutically active dose, but strongly suppresses both primary tumor growth (confirmed in Nemeth-Kellner lymphoma and LLC1 lung cancer models of murine tumor) and spreading of metastases (LLC1).

49th Annual Conference of the German Society for Medical Physics and 21st Annual Conference of the German Section of the ISMRM - Bert, Christoph; Wucherer, Michael; Laun, Frederik B. (Zeitschrift für Medizinische Physik, 2018)
EVALuna2:36480

4D optimization of scanned ion beam tracking therapy for moving tumors - Eley, John Gordon; Newhauser, Wayne David; Lüchtenborg, Robert; Graeff, Christian; Bert, Christoph (Physics in Medicine and Biology, 2014)
Motion mitigation strategies are needed to fully realize the theoretical advantages of scanned ion beam therapy for patients with moving tumors. The purpose of this study was to determine whether a new four-dimensional (4D) optimization approach for scanned-ion-beam tracking could reduce dose to avoidance volumes near a moving target while maintaining target dose coverage, compared to an existing 3D-optimized beam tracking approach. We tested these approaches computationally using a simple 4D geometrical phantom and a complex anatomic phantom, that is, a 4D computed tomogram of the thorax of a lung cancer patient. We also validated our findings using measurements of carbon-ion beams with a motorized film phantom. Relative to 3D-optimized beam tracking, 4D-optimized beam tracking reduced the maximum predicted dose to avoidance volumes by 53% in the simple phantom and by 13% in the thorax phantom. 4D-optimized beam tracking provided similar target dose homogeneity in the simple phantom (standard deviation of target dose was 0.4% versus 0.3%) and dramatically superior homogeneity in the thorax phantom (D5-D95 was 1.9% versus 38.7%). Measurements demonstrated that delivery of 4D-optimized beam tracking was technically feasible and confirmed a 42% decrease in maximum film exposure in the avoidance region compared with 3D-optimized beam tracking. In conclusion, we found that 4D-optimized beam tracking can reduce the maximum dose to avoidance volumes near a moving target while maintaining target dose coverage, compared with 3D-optimized beam tracking.
EVALuna2:18202

5-year results of accelerated partial breast irradiation using sole interstitial multicatheter brachytherapy versus whole-breast irradiation with boost after breast-conserving surgery for low-risk invasive and in-situ carcinoma of the female breast: a ran - Strnad, Vratislav; Ott, Oliver J.; Hildebrandt, Guido; Kauer-Dorner, Daniela; Knauerhase, Hellen; Major, Tibor; Lyczek, Jaroslaw; Guinot, Jose Luis; Dunst, Juergen; Gutierrez Miguelez, Cristina; Slampa, Pavel; Allgaeuer, Michael; et al. (Lancet, 2016)
In a phase 3, randomised, non-inferiority trial, accelerated partial breast irradiation (APBI) for patients with stage 0, I, and IIA breast cancer who underwent breast-conserving treatment was compared with whole-breast irradiation. Here, we present 5-year follow-up results.We did a phase 3, randomised, non-inferiority trial at 16 hospitals and medical centres in seven European countries. 1184 patients with low-risk invasive and ductal carcinoma in situ treated with breast-conserving surgery were centrally randomised to either whole-breast irradiation or APBI using multicatheter brachytherapy. The primary endpoint was local recurrence. Analysis was done according to treatment received. This trial is registered with ClinicalTrials.gov, number NCT00402519.Between April 20, 2004, and July 30, 2009, 551 patients had whole-breast irradiation with tumour-bed boost and 633 patients received APBI using interstitial multicatheter brachytherapy. At 5-year follow-up, nine patients treated with APBI and five patients receiving whole-breast irradiation had a local recurrence; the cumulative incidence of local recurrence was 1.44% (95% CI 0.51-2.38) with APBI and 0.92% (0.12-1.73) with whole-breast irradiation (difference 0.52%, 95% CI -0.72 to 1.75; p=0.42). No grade 4 late side-effects were reported. The 5-year risk of grade 2-3 late side-effects to the skin was 3.2% with APBI versus 5.7% with whole-breast irradiation (p=0.08), and 5-year risk of grade 2-3 subcutaneous tissue late side-effects was 7.6% versus 6.3% (p=0.53). The risk of severe (grade 3) fibrosis at 5 years was 0.2% with whole-breast irradiation and 0% with APBI (p=0.46).The difference between treatments was below the relevance margin of 3 percentage points. Therefore, adjuvant APBI using multicatheter brachytherapy after breast-conserving surgery in patients with early breast cancer is not inferior to adjuvant whole-breast irradiation with respect to 5-year local control, disease-free survival, and overall survival.German Cancer Aid.
EVALuna2:5536

7 Tesla Hippocampal Subfield Analyses In Patients With Medically Refractory Epilepsy And Hippocampal Sclerosis - Roessler, K.; Roesch, Johannes; Coras, R.; Blümcke, Ingmar; Hamer, Hajo; Buchfelder, Michael; Rampp, Stefan; Mennecke, Angelika (EPILEPSIA, 2019)
CRIS-Team WoS Importer:2019-11-15

AAPM Task Group Report 290: Respiratory motion management for particle therapy - Li, Heng; Dong, Lei; Bert, Christoph; Chang, Joe; Flampouri, Stella; Jee, Kyung-Wook; Lin, Liyong; Moyers, Michael; Mori, Shinichiro; Rottmann, Joerg; Tryggestad, Erik; Vedam, Sastry (Medical Physics, 2022)
Dose uncertainty induced by respiratory motion remains a major concern for treating thoracic and abdominal lesions using particle beams. This Task Group report reviews the impact of tumor motion and dosimetric considerations in particle radiotherapy, current motion-management techniques, and limitations for different particle-beam delivery modes (i.e., passive scattering, uniform scanning, and pencil-beam scanning). Furthermore, the report provides guidance and risk analysis for quality assurance of the motion-management procedures to ensure consistency and accuracy, and discusses future development and emerging motion-management strategies. This report supplements previously published AAPM report TG76, and considers aspects of motion management that are crucial to the accurate and safe delivery of particle-beam therapy. To that end, this report produces general recommendations for commissioning and facility-specific dosimetric characterization, motion assessment, treatment planning, active and passive motion-management techniques, image guidance and related decision-making, monitoring throughout therapy, and recommendations for vendors. Key among these recommendations are that: (1) facilities should perform thorough planning studies (using retrospective data) and develop standard operating procedures that address all aspects of therapy for any treatment site involving respiratory motion; (2) a risk-based methodology should be adopted for quality management and ongoing process improvement.
CRIS-Team Scopus Importer:2022-02-11

Abstracts DEGRO 2018 Low-dose irradiation has an impact on bone metabolism as well as on local and systemic immune cell-mediated inflammation - Deloch, Lisa; Rückert, Michael; Seeling, Michaela; Nimmerjahn, Falk; Fietkau, Rainer; Frey, Benjamin; Gaipl, Udo (2018)
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Abstracts DEGRO 2019 Niedrig dosierte Röntgenstrahlung beeinflusst die Makrophagenpolarisation im Zusammenspiel mit Synovialfibroblasten auf eine anti-entzündliche Art und Weise - Deloch, Lisa; Fuchs, Jana; Rückert, Michael; Frey, Benjamin; Gaipl, Udo (2019)
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Abstracts of the 20th Annual Meeting of the German Society for Radiation Oncology (DEGRO), 3-4 July, 2014, Dusseldorf, Germany 20. Jahrestagung der Deutschen Gesellschaft für Radioonkologie - Deloch, Lisa; Derer, Anja; Rühle, Paul-Friedrich; Ott, Oliver; Fietkau, Rainer; Frey, Benjamin; Gaipl, Udo (2014)
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Accelerated Partial Breast Irradiation: Frequent non-professional Phagocytosis in Patients with early, Hormone Receptor-positive Breast Cancer is associated with good Survival - Bauer, Marcus; Schnellhardt, S.; Rosahl, M. -C; Erber, Ramona; Ott, Oliver; Fietkau, Rainer; Distel, Luitpold (STRAHLENTHERAPIE UND ONKOLOGIE, 2020)
CRIS-Team WoS Importer:2020-10-02

Accelerated Partial Breast Irradiation: Identification of High Risk Tumors in Early Hormone Receptor-positive Breast Cancer by Macrophage Shift Classification - Schnellhardt, S.; Erber, Ramona; Büttner-Herold, Maike; Rosahl, M. -C; Ott, Oliver; Strnad, Vratislav; Beckmann, Matthias; King, L.; Hartmann, Arndt; Fietkau, Rainer; Distel, Luitpold (STRAHLENTHERAPIE UND ONKOLOGIE, 2020)
CRIS-Team WoS Importer:2020-10-02

Accelerated partial breast irradiation: Macrophage polarisation shift classification identifies high-risk tumours in early hormone receptor-positive breast cancer - Schnellhardt, Sören; Erber, Ramona; Büttner-Herold, Maike; Rosahl, Marie Charlotte; Ott, Oliver; Strnad, Vratislav; Beckmann, Matthias; King, Lillian; Hartmann, Arndt; Fietkau, Rainer; Distel, Luitpold (Cancers, 2020)
Studies have demonstrated correlations between accumulations of tumour-associated macrophages (TAMs), especially of M2-like phenotype, and increased mortality in advanced breast cancer. We investigated the prognostic potential of both main macrophage phenotypes in early hormone receptor-positive (HR+) breast cancer. The studied cohort of 136 patients participated in an institutional APBI phase II trial. Patient selection was characterized by HR+, small tumour size and no metastasis. Tissue microarrays from pre-RT resection samples were double stained for CD68/CD163 using immunohistochemistry. CD68+/CD163− cells were considered M1-like macrophages and CD68+/CD163+ was representative of M2-like macrophages. M1 and M2 macrophage densities were analysed semi-automatically in the stromal and intraepithelial tumour compartment. Low M1 and high M2 densities were strongly associated with decreased disease-free survival (DFS). Combined TAM phenotype densities were studied after defining a macrophage shift classification: M1-shifted (M1 high, M2 low) and non-shifted (M1 low, M2 low; M1 high, M2 high) tumours entailed a favourable outcome. In contrast, M2-shifted (M1 low, M2 high) TAM populations were associated with extremely reduced DFS. Thus, the full predictive potential of TAMs was revealed in a combined analysis of both phenotypes. The M2-shifted subgroup of tumours is classified as high-risk and probably not suitable for partial breast irradiation.
CRIS-Team Scopus Importer:2020-02-25
Keywords: Accelerated partial breast irradiation; CD163; CD68; Early breast cancer; Hormone receptor-positive; Prognosis; Tumour associated macrophages

Accelerated partial breast irradiation using sole interstitial multicatheter brachytherapy compared with whole-breast irradiation with boost for early breast cancer: 10-year results of a GEC-ESTRO randomised, phase 3, non-inferiority trial - Strnad, Vratislav; Polgár, Csaba; Ott, Oliver; Hildebrandt, Guido; Kauer-Dorner, Daniela; Knauerhase, Hellen; Major, Tibor; Łyczek, Jarosław; Guinot, Jose Luis; Gutierrez Miguelez, Cristina; Slampa, Pavel; Allgäuer, Michael; et al. (The Lancet. Oncology, 2023)
BACKGROUND: Several randomised, phase 3 trials have investigated the value of different techniques of accelerated partial breast irradiation (APBI) for patients with early breast cancer after breast-conserving surgery compared with whole-breast irradiation. In a phase 3 randomised trial, we evaluated whether APBI using multicatheter brachytherapy is non-inferior compared with whole-breast irradiation. Here, we present the 10-year follow-up results. METHODS: We did a randomised, phase 3, non-inferiority trial at 16 hospitals and medical centres in Austria, Czech Republic, Germany, Hungary, Poland, Spain, and Switzerland. Patients aged 40 years or older with early invasive breast cancer or ductal carcinoma in situ treated with breast-conserving surgery were centrally randomly assigned (1:1) to receive either whole-breast irradiation or APBI using multicatheter brachytherapy. Whole-breast irradiation was delivered in 25 daily fractions of 50 Gy over 5 weeks, with a supplemental boost of 10 Gy to the tumour bed, and APBI was delivered as 30·1 Gy (seven fractions) and 32·0 Gy (eight fractions) of high-dose-rate brachytherapy in 5 days or as 50 Gy of pulsed-dose-rate brachytherapy over 5 treatment days. Neither patients nor investigators were masked to treatment allocation. The primary endpoint was ipsilateral local recurrence, analysed in the as-treated population; the non-inferiority margin for the recurrence rate difference (defined for 5-year results) was 3 percentage points. The trial is registered with ClinicalTrials.gov, NCT00402519; the trial is complete. FINDINGS: Between April 20, 2004, and July 30, 2009, 1328 female patients were randomly assigned to whole breast irradiation (n=673) or APBI (n=655), of whom 551 in the whole-breast irradiation group and 633 in the APBI group were eligible for analysis. At a median follow-up of 10·36 years (IQR 9·12-11·28), the 10-year local recurrence rates were 1·58% (95% CI 0·37 to 2·8) in the whole-breast irradiation group and 3·51% (1·99 to 5·03) in the APBI group. The difference in 10-year rates between the groups was 1·93% (95% CI -0·018 to 3·87; p=0·074). Adverse events were mostly grade 1 and 2, in 234 (60%) of 393 participants in the whole-breast irradiation group and 314 (67%) of 470 participants in the APBI group, at 7·5-year or 10-year follow-up, or both. Patients in the APBI group had a significantly lower incidence of treatment-related grade 3 late side-effects than those in the whole-breast irradiation group (17 [4%] of 393 for whole-breast irradiation vs seven [1%] of 470 for APBI; p=0·021; at 7·5-year or 10-year follow-up, or both). At 10 years, the most common type of grade 3 adverse event in both treatment groups was fibrosis (six [2%] of 313 patients for whole-breast irradiation and three [1%] of 375 patients for APBI, p=0·56). No grade 4 adverse events or treatment-related deaths have been observed. INTERPRETATION: Postoperative APBI using multicatheter brachytherapy after breast-conserving surgery in patients with early breast cancer is a valuable alternative to whole-breast irradiation in terms of treatment efficacy and is associated with fewer late side-effects. FUNDING: German Cancer Aid, Germany.
CRIS-Team Scopus Importer:2023-03-10

Accelerated partial breast irradiation with external beam radiotherapy : First results of the German phase 2 trial - Ott, Oliver J.; Strnad, Vratislav; Stillkrieg, Wilhelm; Uter, Wolfgang; Beckmann, Matthias; Fietkau, Rainer (Strahlentherapie und Onkologie, 2017)
BACKGROUND AND PURPOSE: To evaluate the feasibility and efficacy of external beam three-dimensional (3D) conformal accelerated partial breast irradiation (APBI) for selected patients with early breast cancer. PATIENTS AND METHODS: Between 2011 and 2016, 72 patients were recruited for this prospective phase 2 trial. Patients were eligible for APBI if they had histologically confirmed breast cancer or pure ductal carcinoma in situ (DCIS), a tumor diameter ≤3 cm, clear resection margins ≥2 mm, no axillary lymph node involvement, no distant metastases, tumor bed clips, and were aged ≥50 years. Patients were excluded if mammography showed a multicentric invasive growth pattern, or if they had residual diffuse microcalcifications postoperatively, an extensive intraductal component, or vessel invasion. Patients received 3D conformal external beam APBI with a total dose of 38 Gy in 10 fractions in 1-2 weeks. The trial had been registered at the German Clinical Trials Register, DRKS-ID: DRKS00004417. RESULTS: Median follow-up was 25.5 months (range 1-61 months). Local control was maintained in 71 of 72 patients. The 3‑year local recurrence rate was 2.1% (95% confidence interval, CI: 0-6.1%). Early toxicity (grade 1 radiodermatitis) was seen in 34.7% (25/72). Late side effects ≥ grade 3 did not occur. Cosmetic results were rated as excellent/good in 96.7% (59/61). CONCLUSION: APBI with external beam radiotherapy techniques is feasible with low toxicity and, according to the results of the present and other studies, on the way to becoming a standard treatment option for a selected subgroup of patients.
EVALuna2:32915

Accelerated partial breast irradiation with external beam radiotherapy: results of the German phase 2-trial - Ott, O. J.; Strnad, Vratislav; Sillkrieg, W.; Uter, Wolfgang; Beckmann, Matthias; Fietkau, Rainer (STRAHLENTHERAPIE UND ONKOLOGIE, 2019)
CRIS-Team WoS Importer:2019-06-07

Accelerating Photostability Evaluation of Perovskite Films through Intelligent Spectral Learning-Based Early Diagnosis - Liu, Ziyi; Zhang, Jiyun; Rao, Gaofeng; Peng, Zijian; Huang, Yixing; Arnold, Simon; Liu, Bowen; Deng, Can; Li, Chen; Li, Heng; Zhi, Hanxiang; Zhang, Zhi; et al. (ACS Energy Letters, 2024)
Obtaining highly stable metal-halide perovskites is crucial for the commercialization of perovskite solar cells. However, current methods for evaluating perovskite stability mainly rely on a time-consuming and resource-intensive aging process. Here, we demonstrate a spectral learning-based methodology that enables the prediction of perovskite stability by leveraging the features in photoluminescence and absorption spectra of fresh perovskite films. This methodology circumvents the long-term aging process by combining a custom-developed spectral feature extraction algorithm and an integrated voting machine learning model. By integration of the early diagnosis program with high-throughput experiments, the prediction accuracy for stable perovskites exceeds 86% in 160 fresh samples. The universality is further examined by another batch of 224 fresh samples fabricated through different processing conditions. Finally, the early diagnosis of perovskite films is successfully translated to enhanced stability in perovskite solar cells. Our work provides a new pathway to accelerate the discovery and development of stable perovskite films.
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Accumulation of the delivered treatment dose in volumetric modulated arc therapy with breath-hold for pancreatic cancer patients based on daily cone beam computed tomography images with limited field-of-view - Ziegler, Marc; Nakamura, Mitsuhiro; Hirashima, Hideaki; Ashida, Ryo; Yoshimura, Michio; Bert, Christoph; Mizowaki, Takashi (Medical Physics, 2019)
Background and purpose: Inter-fractional changes of the daily anatomy of the patient are a source of error in radiotherapy. This effect is especially present in the abdomen, where there are daily differences in the filling of the stomach or the intestines. This study investigated the impact of inter-fractional changes of pancreatic cancer patients who underwent breath-hold volumetric modulated arc therapy on the applied dose by using deformable image registration. Material and methods: Deformable image registration was used to determine a displacement field which maps the computed tomography (CT) used for treatment planning onto daily breath-hold cone-beam CT images with limited field-of-view (FOV) which were acquired at the beginning of every treatment fraction. Different B-spline registration methods utilizing different metrics and regularizations were used and compared. The resulting deformed planning CT images were used to calculate the dose distributions on the anatomy of the day which can therefore be seen as a good estimation of the actually delivered dose during the treatment fractions. Additionally, the accumulated dose distribution was determined by accumulating all daily dose distributions using inverted deformation fields. The calculated dose distributions were then compared to the planned dose by comparison of dose volume histograms and dosimetric volumetric indices. Results: Best registration results were obtained using a gradient magnitude metric and a regularization of λ = 0.05. The accumulated dose distributions showed that the mean dose delivered to the clinical target volume was on median reduced by 0.61 Gy after 15 fractions from the planned dose. For the organs at risk, the accumulated dose distributions were still fulfilling all clinical goals for the patient cohort used in this study. It was found that rotating and shearing motions of the tumor led to a greater reduction in the mean target dose which correlated with the proximity of the target to the spine (r = 0.54, P = 0.038). Conclusion: With the proposed method, it is possible to generate a deformed planning CT image which matches the anatomy of the day based on cone beam computed tomography images with a limited FOV and calculating the dose distribution of the day. The dosimetric impact of the inter-fractional variations was small for most patients but showed larger deviations if the tumor is located in close proximity to the spine.
CRIS-Team Scopus Importer:2019-06-28
Keywords: breath-hold; deformable image registration; inter-fractional changes; pancreatic cancer

Accuracy of MRI-CT registration in brain stereotactic radiotherapy: Impact of MRI acquisition setup and registration method - Masitho, Siti; Putz, Florian; Mengling, Veit; Reißig, Lisa; Voigt, Raphaela; Bäuerle, Tobias; Janka, Rolf Matthias; Fietkau, Rainer; Bert, Christoph (Zeitschrift für Medizinische Physik, 2022)
Background: In MR-based radiotherapy (RT), MRI images are co-registered to the planning CT to leverage MR image information for RT planning. Especially in brain stereotactic RT, where typical CTV-PTV margins are 1-2 mm, high registration accuracy is critical. Several factors influence the registration accuracy, including the acquisition setup during MR simulation and the registration methods. Purpose: In this work, the impact of the MRI acquisition setup and registration method was evaluated in the context of brain RT, both geometrically and dosimetrically. Methods and Materials: MRI of 20 brain radiotherapy patients was acquired in two MRI acquisition setups (RT and diagnostic). Three different automatic registration tools provided by three treatment planning systems were used to rigidly register both MRIs and CT in addition to the clinical registration. Segmentation-based evaluation using Hausdorff Distance (HD)/Dice Similarity Coefficient and landmark-based evaluation were used as evaluation metrics. Dose-volume-histograms were evaluated for target volumes and various organs at risks. Results: MRI acquisition in the RT setup provided a similar head extension as compared to the planning CT. The registration method had a more significant influence than the acquisition setup (Wilcoxon signed-rank test, p<0.05). When registering using a less optimal registration method, the RT setup improved the registration accuracy compared to the diagnostic setup (Difference: ΔMHD = 0.16 mm, ΔHDP95 = 0.64 mm, mean Euclidean distance (ΔmEuD) = 2.65 mm). Different registration methods and acquisition setups lead to the variation of the clinical DVH. Acquiring MRI in the RT setup can improve PTV and GTV coverage compared to the diagnostic setup. Conclusions: Both MRI acquisition setup and registration method influence the MRI-CT registration accuracy in brain RT patients geometrically and dosimetrically. MR-simulation in the RT setup assures optimal registration accuracy if automatic registration is impaired, and therefore recommended for brain RT.
CRIS-Team Scopus Importer:2022-11-11
Keywords: Brain radiotherapy; Intracranial stereotactic radiotherapy; Magnetic-resonance imaging; Patient immobilization; Registration

A clinician's plea to test glioma patients for CMV - Goerig, Nicole; Frey, Benjamin; Überla, Klaus; Gaipl, Udo; Fietkau, Rainer (Neuro-Oncology, 2017)
EVALuna2:32871

A comparison between p16-positive head and neck cancer of unknown primary (HPV-HNCUP) and oropharyngeal squamous cell carcinoma (HPV-OPSCC): are they the same disease? - Balk, Matthias; Rupp, Robin; Sievert, Matti; Mantsopoulos, Konstantinos; Allner, Moritz; Grundtner, Philipp; Müller-Hübner, Sarina; Eckstein, Markus; Iro, Heinrich; Hecht, Markus; Gostian, Antoniu-Oreste (European Archives of Oto-Rhino-Laryngology, 2023)
Introduction: The following study aimed to answer the question if HPV-HNCUP and HPV-OPSCC are the same disease. Propensity score matching (PSM) was used to compare the oncological outcomes of both groups, in particular the 5-year overall survival rate (OS), the 5-year disease specific survival rate (DSS) and the 5-year progression free survival rate (PFS). Materials and methods: Firstly, between January 1st, 2007, and March 31st, 2020 a total of 131 patients were treated with HNCUP at our Department. Out of these, 21 patients with a confirmed positive p16 status were referred to surgery followed by adjuvant therapy. Secondly, between January 1st, 2000, and January 31st, 2017, a total of 1596 patients were treated with an OPSSC at our Department. Out of these, 126 patients with a confirmed positive p16 status were referred to surgery followed by adjuvant therapy. After PSM, 84 patients with HPV-OPSCC and 21 HPV-HNCUP remained in the study for further comparison. Results: The OS was 63.5% (95% CI 39.4–87.6) for HPV-HNCUP and 88.9% (95% CI 90.4–100.0) for HPV-OPSCC patients and therefore, significantly lower for the first mentioned (p = 0.013). The DSS was also significantly impaired for HPV-HNCUP (71.0%, 95% CI 46.3–95.7), in comparison with HPV-OPSCC patients (95.5%, 95% CI 90.4–100.0; p = 0.002). The PFS for HPV-HNCUP patients was lower (75.6%, 95% CI 54.0–97.2) yet not significantly different to HPV-OPSCC (90.4%, 95% CI 83.5–97.3; p = 0.067). Conclusions: The results presented demonstrate a significant reduced OS and DSS for HPV-HNCUP patients. Accordingly, in our study HPV-HNCUP and HPV-OPSCC are two different entities with a different oncological outcome.
CRIS-Team Scopus Importer:2023-08-11
Keywords: Cancer of unknown primary; Head and neck cancer; HPV-HNCUP; HPV-OPSCC; Neck dissection; Oropharyngeal cancer

A Comparison of Single- and Multiparametric MRI Models for Differentiation of Recurrent Glioblastoma from Treatment-Related Change - Eisenhut, Felix; Engelhorn, Tobias; Arinrad, Soheil; Brandner, Sebastian; Coras, Roland; Putz, Florian; Fietkau, Rainer; Dörfler, Arnd; Schmidt, Manuel (Diagnostics, 2021)
To evaluate single- and multiparametric MRI models to differentiate recurrent glioblastoma (GBM) and treatment-related changes (TRC) in clinical routine imaging. Selective and unselective apparent diffusion coefficient (ADC) and minimum, mean, and maximum cerebral blood volume (CBV) measurements in the lesion were performed. Minimum, mean, and maximum ratios(CBV) (CBVlesion to CBVhealthy white matter) were computed. All data were tested for lesion discrimination. A multiparametric model was compiled via multiple logistic regression using data demonstrating significant difference between GBM and TRC and tested for its diagnostic strength in an independent patient cohort. A total of 34 patients (17 patients with recurrent GBM and 17 patients with TRC) were included. ADC measurements showed no significant difference between both entities. All CBV and ratios(CBV) measurements were significantly higher in patients with recurrent GBM than TRC. A minimum CBV of 8.5, mean CBV of 116.5, maximum CBV of 327 and ratio(CBV) (minimum) of 0.17, ratio(CBV) (mean) of 2.26 and ratio(CBV) (maximum) of 3.82 were computed as optimal cut-off values. By integrating these parameters in a multiparametric model and testing it in an independent patient cohort, 9 of 10 patients, i.e., 90%, were classified correctly. The multiparametric model further improves radiological discrimination of GBM from TRC in comparison to single-parameter approaches and enables reliable identification of recurrent tumors.
CRIS-Team WoS Importer:2022-01-07

A comprehensive quality assurance program for four-dimensional computed tomography in radiotherapy - Bakkali Tahiri, Jinane; Kyndt, Martin; Dhont, Jennifer; Gulyban, Akos; Szkitsak, Juliane; Bogaert, Evelien; Reynaert, Nick; Burghelea, Manuela (Physics and Imaging in Radiation Oncology, 2023)
This study aimed to develop and validate a comprehensive, reproducible and automatic 4DCT Quality Assurance (QA) workflow (QAMotion) that evaluates image accuracy across various regular and irregular breathing patterns. Volume and amplitude deviations, CT number accuracy, and spatial integrity were used as evaluation metrics. For repeatability tests, tolerances were respected with a mean CT number deviation < 10 HU, volume deviation < 2% and diameter and amplitude deviation < 2 mm except for irregular amplitude curves for which an amplitude deviation up to 6 mm was measured. QAMotion was able to flag image artefacts for our clinical 4DCT system.
CRIS-Team Scopus Importer:2023-08-25
Keywords: 4DCT; Quality assurance program; Radiotherapy; Tumor motion

Acquired temozolomide resistance in human glioblastoma cell line U251 is caused by mismatch repair deficiency and can be overcome by lomustine - Stritzelberger, Jenny; Distel, Luitpold; Buslei, R.; Fietkau, Rainer; Putz, Florian (Clinical & Translational Oncology, 2018)
PURPOSE: Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor in adults. While the alkylating agent temozolomide (TMZ) has prolonged overall survival, resistance evolution represents an important clinical problem. Therefore, we studied the effectiveness of radiotherapy and CCNU in an in vitro model of acquired TMZ resistance. METHODS: We studied the MGMT-methylated GBM cell line U251 and its in vitro derived TMZ-resistant subline, U251/TMZ-R. Cytotoxicity of TMZ, CCNU, and radiation was tested. Both cell lines were analyzed for MGMT promotor status and expression of mismatch repair genes (MMR). The influence of MMR inhibition by cadmium chloride (CdCl2) on the effects of both drugs was evaluated. RESULTS: During the resistance evolution process in vitro, U251/TMZ-R developed MMR deficiency, but MGMT status did not change. U251/TMZ-R cells were more resistant to TMZ than parental U251 cells (cell viability: 92.0% in U251/TMZ-R/69.2% in U251; p = 0.032) yet more sensitive to CCNU (56.4%/80.8%; p = 0.023). The effectiveness of radiotherapy was not reduced in the TMZ-resistant cell line. Combination of CCNU and TMZ showed promising results for both cell lines and overcame resistance. CdCl2-induced MMR deficiency increased cytotoxicity of CCNU. CONCLUSION: Our results confirm MMR deficiency as a crucial process for resistance evolution to TMZ. MMR-deficient TMZ-resistant GBM cells were particularly sensitive to CCNU and to combined CCNU/TMZ. Effectiveness of radiotherapy was preserved in TMZ-resistant cells. Consequently, CCNU might be preferentially considered as a treatment option for recurrent MGMT-methylated GBM and may even be suitable for prevention of resistance evolution in primary treatment.
EVALuna2:34594

Acriflavine-Functionalized Silica@Manganese Ferrite Nanostructures for Synergistic Radiation and Hypoxia Therapies - Eckenberger, Elisabeth; Raczka, Theodor; Neuhuber, Winfried; Distel, Luitpold; Klein, Stefanie (ACS Applied Bio Materials, 2023)
Mesoporous and nonmesoporous SiO2@MnFe2O4 nanostructures were loaded with the hypoxia-inducible factor-1 inhibitor acriflavine for combined radiation and hypoxia therapies. The X-ray irradiation of the drug-loaded nanostructures not only triggered the release of the acriflavine inside the cells but also initiated an energy transfer from the nanostructures to surface-adsorbed oxygen to generate singlet oxygen. While the drug-loaded mesoporous nanostructures showed an initial drug release before the irradiation, the drug was primarily released upon X-ray radiation in the case of the nonmesoporous nanostructures. However, the drug loading capacity was less efficient for the nonmesoporous nanostructures. Both drug-loaded nanostructures proved to be very efficient in irradiated MCF-7 multicellular tumor spheroids. The damage of these nanostructures toward the nontumorigenic MCF-10A multicellular spheroids was very limited because of the small number of nanostructures that entered the MCF-10A spheroids, while similar concentrations of acriflavine without nanostructures were toxic for the MCF-10A spheroids.
CRIS-Team Scopus Importer:2023-09-29
Keywords: drug delivery; hypoxia; magnetic mesoporous silica@MnFe2O4 nanoparticles; magnetic silica@MnFe2O4 nanoparticle acriflavine; multicellular tumor spheroids; radiation therapy

Activation of Epithelial Signal Transducer and Activator of Transcription 1 by Interleukin 28 Controls Mucosal Healing in Mice With Colitis and Is Increased in Mucosa of Patients With Inflammatory Bowel Disease. - Chiriac, Mircea-Teodor; Buchen, Barbara; Wandersee, Alexandra; Hundorfean, Gheorghe; Günther, Claudia; Bourjau, Yvonne; Doyle, Sean E.; Frey, Benjamin; Ekici, Arif Bülent; Büttner, Christian; Weigmann, Benno; Atreya, Raja; et al. (Gastroenterology, 2017)
We investigated the roles of interleukin 28A (also called IL28A or interferon λ2) in intestinal epithelial cell (IEC) activation, studying its effects in mouse models of inflammatory bowel diseases (IBD) and intestinal mucosal healing. and Stat1IEC-KO mice also developed more severe colitis in response to oxazolone than control mice. We found IL28 to induce phosphorylation (activation) of STAT1 in epithelial cells, leading to their proliferation in organoid culture. Administration of IL28 to mice with induced colonic wounds promoted mucosal healing. ). We used high-resolution mini-endoscopy and in vivo imaging methods to assess colitis progression. We used 3-dimensional small intestine and colon organoids, along with RNA-Seq and gene ontology methods, to characterize the effects of IL28 on primary IECs. We studied the effects of IL28 on the human intestinal cancer cell line Caco-2 in a wound-healing assay, and in mice colon wounds. Colonic biopsies and resected tissue from patients with IBD (n = 62) and patients without colon inflammation (controls, n = 23) were analyzed by quantitative polymerase chain rection to measure expression of IL28A, IL28RA, and other related cytokines; biopsy samples were also analyzed by immunofluorescence to identify sources of IL28 production. IECs were isolated from patient tissues and incubated with IL28; signal transducer and activator of transcription 1 (STAT1) phosphorylation was measured by immunoblots and confocal imaging. IL28 controls proliferation of IECs in mice with colitis and accelerates mucosal healing by activating STAT1. IL28 might be developed as a therapeutic agent for patients with IBD. BACKGROUND & AIMS RESULTS METHODS CONCLUSIONS
Keywords: Crohn’s Disease; Interferon λ; Ulcerative Colitis; Wound Healing

Activation of Epithelial Signal Transducer and Activator of Transcription 1 by Interleukin 28 Controls Mucosal Healing in Mice With Colitis and Is Increased in Mucosa of Patients With Inflammatory Bowel Disease - Chiriac, Mircea-Teodor; Buchen, Barbara; Wandersee, Alexandra; Hundorfean, Gheorghe; Günther, Claudia; Bourjau, Yvonne; Doyle, Sean E.; Frey, Benjamin; Ekici, Arif Bülent; Büttner, Christian; Weigmann, Benno; Atreya, Raja; et al. (Gastroenterology, 2017)
We investigated the roles of interleukin 28A (also called IL28A or interferon λ2) in intestinal epithelial cell (IEC) activation, studying its effects in mouse models of inflammatory bowel diseases (IBD) and intestinal mucosal healing. and Stat1IEC-KO mice also developed more severe colitis in response to oxazolone than control mice. We found IL28 to induce phosphorylation (activation) of STAT1 in epithelial cells, leading to their proliferation in organoid culture. Administration of IL28 to mice with induced colonic wounds promoted mucosal healing. ). We used high-resolution mini-endoscopy and in vivo imaging methods to assess colitis progression. We used 3-dimensional small intestine and colon organoids, along with RNA-Seq and gene ontology methods, to characterize the effects of IL28 on primary IECs. We studied the effects of IL28 on the human intestinal cancer cell line Caco-2 in a wound-healing assay, and in mice colon wounds. Colonic biopsies and resected tissue from patients with IBD (n = 62) and patients without colon inflammation (controls, n = 23) were analyzed by quantitative polymerase chain rection to measure expression of IL28A, IL28RA, and other related cytokines; biopsy samples were also analyzed by immunofluorescence to identify sources of IL28 production. IECs were isolated from patient tissues and incubated with IL28; signal transducer and activator of transcription 1 (STAT1) phosphorylation was measured by immunoblots and confocal imaging. IL28 controls proliferation of IECs in mice with colitis and accelerates mucosal healing by activating STAT1. IL28 might be developed as a therapeutic agent for patients with IBD. BACKGROUND & AIMS RESULTS METHODS CONCLUSIONS
Keywords: Crohn’s Disease; Interferon λ; Ulcerative Colitis; Wound Healing

Activation of Epithelial Signal Transducer and Activator of Transcription 1 by Interleukin 28 Controls Mucosal Healing in Mice With Colitis and Is Increased in Mucosa of Patients With Inflammatory Bowel Disease - Chiriac, Mircea T.; Buchen, Barbara; Wandersee, Alexandra; Hundorfean, Gheorghe; Günther, Claudia; Bourjau, Yvonne; Doyle, Sean E.; Frey, Benjamin; Ekici, Arif Bülent; Büttner, Christian; Weigmann, Benno; Atreya, Raja; et al. (Gastroenterology, 2017)
We investigated the roles of interleukin 28A (also called IL28A or interferon ?2) in intestinal epithelial cell (IEC) activation, studying its effects in mouse models of inflammatory bowel diseases (IBD) and intestinal mucosal healing.Colitis was induced in C57BL/6JCrl mice (controls), mice with IEC-specific disruption of Stat1 (Stat1IEC-KO), mice with disruption of the interferon ? receptor 1 gene (Il28ra(-/-)), and mice with disruption of the interferon regulatory factor 3 gene (Irf3(-/-)), with or without disruption of Irf7 (Irf7(-/-)). We used high-resolution mini-endoscopy and in vivo imaging methods to assess colitis progression. We used 3-dimensional small intestine and colon organoids, along with RNA-Seq and gene ontology methods, to characterize the effects of IL28 on primary IECs. We studied the effects of IL28 on the human intestinal cancer cell line Caco-2 in a wound-healing assay, and in mice colon wounds. Colonic biopsies and resected tissue from patients with IBD (n = 62) and patients without colon inflammation (controls, n = 23) were analyzed by quantitative polymerase chain rection to measure expression of IL28A, IL28RA, and other related cytokines; biopsy samples were also analyzed by immunofluorescence to identify sources of IL28 production. IECs were isolated from patient tissues and incubated with IL28; signal transducer and activator of transcription 1 (STAT1) phosphorylation was measured by immunoblots and confocal imaging.Lamina propria cells in colon tissues of patients with IBD, and mice with colitis, had increased expression of IL28 compared with controls; levels of IL28R were increased in the colonic epithelium of patients with IBD and mice with colitis. Administration of IL28 induced phosphorylation of STAT1 in primary human and mouse IECs, increasing with dose. Il28ra(-/-), Irf3(-/-), Irf3(-/-)Irf7(-/-), as well as Stat1IEC-KO mice, developed more severe colitis after administration of dextran sulfate sodium than control mice, with reduced epithelial restitution. Il28ra(-/-) and Stat1IEC-KO mice also developed more severe colitis in response to oxazolone than control mice. We found IL28 to induce phosphorylation (activation) of STAT1 in epithelial cells, leading to their proliferation in organoid culture. Administration of IL28 to mice with induced colonic wounds promoted mucosal healing.IL28 controls proliferation of IECs in mice with colitis and accelerates mucosal healing by activating STAT1. IL28 might be developed as a therapeutic agent for patients with IBD.
EVALuna2:9356

Adaptive radiotherapy and the dosimetric impact of inter- and intrafractional motion on the planning target volume for prostate cancer patients - Böckelmann, Felix; Putz, Florian; Kallis, Karoline; Lettmaier, Sebastian; Fietkau, Rainer; Bert, Christoph (Strahlentherapie und Onkologie, 2020)
Purpose: To investigate the dosimetric influence of daily interfractional (inter) setup errors and intrafractional (intra) target motion on the planning target volume (PTV) and the possibility of an offline adaptive radiotherapy (ART) method to correct larger patient positioning uncertainties in image-guided radiotherapy for prostate cancer (PCa). Materials and methods: A CTV (clinical target volume)-to-PTV margin ranging from 15 mm in LR (left-right) and SI (superior-inferior) and 5–10 mm in AP (anterior-posterior) direction was applied to all patients. The dosimetric influence of this margin was retrospectively calculated by analysing systematic and random components of inter and intra errors of 31 consecutive intermediate- and high-risk localized PCa patients using daily cone beam computed tomography and kV/kV (kilo-Voltage) imaging. For each patient inter variation was assessed by observing the first 4 treatment days, which led to an offline ART-based treatment plan in case of larger variations. Results:: Systematic inter uncertainties were larger (1.12 in LR, 2.28 in SI and 1.48 mm in AP) than intra systematic errors (0.44 in LR, 0.69 in SI and 0.80 mm in AP). Same findings for the random error in SI direction with 3.19 (inter) and 2.30 mm (intra), whereas in LR and AP results were alike with 1.89 (inter) and 1.91 mm (intra) and 2.10 (inter) and 2.27 mm (intra), respectively. The calculated margin revealed dimensions of 4–5 mm in LR, 8–9 mm in SI and 6–7 mm in AP direction. Treatment plans which had to be adapted showed smaller variations with 1.12 (LR) and 1.72 mm (SI) for Σ and 4.17 (LR) and 3.75 mm (SI) for σ compared to initial plans with 1.77 and 2.62 mm for Σ and 4.46 and 5.39 mm for σ in LR and SI, respectively. Conclusion: The currently clinically used margin of 15 mm in LR and SI and 5–10 mm in AP direction includes inter and intra uncertainties. The results show that offline ART is feasible which becomes a necessity with further reductions in PTV margins.
CRIS-Team Scopus Importer:2020-03-20
Keywords: Cone beam computed tomography; Drinking protocol; Endorectal balloon; Margin calculation

A Delphi study and International Consensus Recommendations: The use of bolus in the setting of postmastectomy radiation therapy for early breast cancer - Kaidar-Person, Orit; Dahn, Hannah M.; Nichol, Alan M.; Boersma, Liesbeth J.; de Ruysscher, Dirk; Meattini, Icro; Pignol, Jean Philippe; Aristei, Cynthia; Belkacemi, Yazid; Benjamin, Dori; Bese, Nuran; Coles, Charlotte E.; et al. (Radiotherapy and Oncology, 2021)
Bolus serves as a tissue equivalent material that shifts the 95–100% isodose line towards the skin and subcutaneous tissue. The need for bolus for all breast cancer patients planned for postmastectomy radiation therapy (PMRT) has been questioned. The work was initiated by the faculty of the European SocieTy for Radiotherapy & Oncology (ESTRO) breast cancer courses and represents a multidisciplinary international breast cancer expert collaboration to optimize PMRT. Due to the lack of randomised trials evaluating the benefits of bolus, we designed a stepwise project to evaluate the existing evidence about the use of bolus in the setting of PMRT to achieve an international consensus for the indications of bolus in PMRT, based on the Delphi method.
CRIS-Team Scopus Importer:2021-10-22
Keywords: Bolus; Breast cancer; Mastectomy; PMRT; Radiation therapy; Tissue compensator

Adherence to oral anticoagulation in secondary stroke prevention - the first year of direct oral anticoagulants - Sauer, Rolf; Sauer, Eva-Maria; Bobinger, Tobias; Blinzler, Christian; Huttner, Hagen; Schwab, Stefan; Köhrmann, Martin (Journal of Stroke and Cerebrovascular Diseases, 2015)
Patients with ischemic stroke caused by atrial fibrillation (AF) have a high risk of recurrence without adequate secondary prevention with oral anticoagulation (OAC). We investigated adherence to OAC in the first year after introduction of direct oral anticoagulants.In 284 appropriate patients, the rate of anticoagulation (AC) at discharge, adherence at 90 days and 1 year, changes between substances, and predictors for adherence to AC were analyzed. Functional outcome was assessed using the modified Rankin Scale score.AC was initiated in 70.3% of survivors before discharge. In these patients, only 8.6% and 9.9% discontinued AC after 90 days and 1 year, respectively. In 22.1%, AC was recommended but not started before discharge. Only 53.2% of them received AC at 90 days, increasing to 67.5% at 1 year. A total of 7.6% of patients were deemed unsuitable for AC, none of them subsequently received AC. Overall, 85.4% of patients suitable for AC were treated at 1-year follow-up. No independent predictors for withholding AC were identified. Switching of medication occurred in only a minority of patients within the first year.AC is feasible in more than 90% patients with acute ischemic stroke and AF. When initiated during the acute hospital stay, AC is discontinued in only a minority of patients. However, if AC is recommended but not started during initial hospitalization the rate of AC treatment at 90 days and 1 year is much lower. Therefore, AC should be initiated within the acute hospital stay whenever possible.
EVALuna2:22269

Adhesion molecule expression and function of primary endothelial cells in benign and malignant tissues correlates with proliferation - Sievert, Wolfgang; Tapio, Soile; Breuninger, Stephanie; Gaipl, Udo; Andratschke, Nicolaus; Trott, Klaus-Ruediger; Multhoff, Gabriele (PLoS ONE, 2014)
Comparative analysis of the cellular biology of the microvasculature in different tissues requires the availability of viable primary endothelial cells (ECs). This study describes a novel method to isolate primary ECs from healthy organs, repair blastemas and tumors as examples of non-proliferating and proliferating benign and malignant tissues and their functional characterization.Single cell suspensions from hearts, lungs, repair blastemas and tumors were incubated consecutively with an anti-CD31 antibody and magnetic micro-beads, coupled to a derivative of biotin and streptavidin, respectively. Following magnetic bead separation, CD31-positive ECs were released by biotin-streptavidin competition. In the absence of micro-beads, ECs became adherent to plastic surfaces. ECs from proliferating repair blastemas and tumors were larger and exhibited higher expression densities of CD31, CD105 and CD102 compared to those from non-proliferating normal tissues such as heart and lung. The expression density of CD34 was particularly high in tumor-derived ECs, and that of CD54 and CD144 in ECs of repair blastemas. Functionally, ECs of non-proliferating and proliferating tissues differed in their capacity to form tubes in matrigel and to align under flow conditions.This method provides a powerful tool to generate high yields of viable, primary ECs of different origins. The results suggest that an altered expression of adhesion molecules on ECs in proliferating tissues contribute to loss of EC function that might cause a chaotic tumor vasculature.
EVALuna2:18206

A disease-specific enteral nutrition formula improves nutritional status and functional performance in patients with head and neck and esophageal cancer undergoing chemoradiotherapy: Results of a randomized, controlled, multicenter trial - Fietkau, Rainer; Lewitzki, Victor; Kuhnt, Thomas; Hoelscher, Tobias; Hess, Clemens-F.; Berger, Bernhard; Wiegel, Thomas; Roedel, Claus; Niewald, Marcus; Hermann, Robert M.; Lubgan, Dorota (Cancer, 2013)
Background: In patients with head and neck and esophageal tumors, nutritional status may deteriorate during concurrent chemoradiotherapy (CRT). The aim of this study was to investigate the influence of enteral nutrition enriched with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on body composition and nutritional and functional status. Methods: In a controlled, randomized, prospective, double-blind, multicenter study, 111 patients with head and neck and esophageal cancer undergoing concurrent CRT received either an enteral standard nutrition (control group) or disease-specific enteral nutrition Supportan®-containing EPA+DHA (experimental group) via percutaneous endoscopic gastrostomy. The primary endpoint was the change of body cell mass (BCM) following CRT at weeks 7 and 14 compared with the baseline value. Secondary endpoints were additional parameters of body composition, anthropometric parameters, and nutritional and functional status. Results: The primary endpoint of the study, improvement in BCM, reached borderline statistical significance. Following CRT, patients with experimental nutrition lost only 0.82 ± 0.64 kg of BCM compared with 2.82 ± 0.77 kg in the control group (P =.055). The objectively measured nutritional parameters, such as body weight and fat-free mass, showed a tendency toward improvement, but the differences were not significant. The subjective parameters, in particular the Kondrup score (P =.0165) and the subjective global assessment score (P =.0065) after follow-up improved significantly in the experimental group, compared with the control group. Both enteral regimens were safe and well tolerated. CONCLUSION Enteral nutrition with EPA and DHA may be advantageous in patients with head and neck or esophageal cancer by improving parameters of nutritional and functional status during CRT. © 2013 American Cancer Society.
Created from Fastlane, Scopus look-up
Keywords: concurrent chemoradiotherapy; docosahexaenoic acid; eicosapentaenoic acid; esophageal cancer; head and neck cancer; nutritional status; nutritional therapy; supportive care

Advance directives in patients with head and neck cancer - status quo and factors influencing their creation - Allner, Moritz; Gostian, Magdalena; Rupp, Robin; Allner, Clarissa; Mantsopoulos, Konstantinos; Ostgathe, Christoph; Iro, Heinrich; Hecht, Markus; Gostian, Antoniu-Oreste; Balk, Matthias (BMC Palliative Care, 2022)
Background: Advance Care Planning including living wills and durable powers of attorney for healthcare is a highly relevant topic aiming to increase patient autonomy and reduce medical overtreatment. Data from patients with head and neck cancer (HNC) are not currently available. The main objective of this study was to survey the frequency of advance directives (AD) in patients with head and neck cancer. Methods: In this single center cross-sectional study, we evaluated patients during their regular follow-up consultations at Germany’s largest tertiary referral center for head and neck cancer, regarding the frequency, characteristics, and influencing factors for the creation of advance directives using a questionnaire tailored to our cohort. The advance directives included living wills, durable powers of attorney for healthcare, and combined directives. Results: Four hundred and forty-six patients were surveyed from 07/01/2019 to 12/31/2019 (response rate = 68.9%). The mean age was 62.4 years (SD 11.9), 26.9% were women (n = 120). 46.4% of patients (n = 207) reported having authored at least one advance directive. These documents included 16 durable powers of attorney for healthcare (3.6%), 75 living wills (16.8%), and 116 combined directives (26.0%). In multivariate regression analysis, older age (OR ≤ 0.396, 95% CI 0.181–0.868; p = 0.021), regular medication (OR = 1.896, 95% CI 1.029–3.494; p = 0.040), and the marital status (“married”: OR = 2.574, 95% CI 1.142–5.802; p = 0.023; and “permanent partnership”: OR = 6.900, 95% CI 1.312–36.295; p = 0.023) emerged as significant factors increasing the likelihood of having an advance directive. In contrast, the stage of disease, the therapeutic regimen, the ECOG status, and the time from initial diagnosis did not correlate with the presence of any type of advance directive. Ninety-one patients (44%) with advance directives created their documents before the initial diagnoses of head and neck cancer. Most patients who decide to draw up an advance directive make the decision themselves or are motivated to do so by their immediate environment. Only 7% of patients (n = 16) actively made a conscious decision not create an advance directive. Conclusion: Less than half of head and neck cancer patients had created an advance directive, and very few patients have made a conscious decision not to do so. Older and comorbid patients who were married or in a permanent partnership had a higher likelihood of having an appropriate document. Advance directives are an essential component in enhancing patient autonomy and allow patients to be treated according to their wishes even when they are unable to consent. Therefore, maximum efforts are advocated to increase the prevalence of advance directives, especially in head and neck cancer patients, whose disease often takes a crisis-like course.
CRIS-Team Scopus Importer:2022-04-22
Keywords: Advance care planning; Advance directive; Head and neck Cancer; Living will; Patient autonomy; Power of attorney for healthcare

Advanced Multimodal Methods for Cranial Pseudo-CT Generation Validated by IMRT and VMAT Radiation Therapy Plans - Speier, Christoph; Pileggi, Giampaolo; Izquierdo-Garcia, David; Catana, Ciprian; Sharp, Gregory C.; Spadea, Maria Francesca; Bert, Christoph; Seco, Joao (International Journal of Radiation Oncology Biology Physics, 2018)
PURPOSE: To investigate advanced multimodal methods for pseudo-computed tomography (CT) generation from standard magnetic resonance imaging sequences and to validate the results by intensity-modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) plans. We present 2 novel methods that employ key techniques to enhance pseudo-CTs and investigate the effect on image quality and applicability for IMRT and VMAT planning. MATERIALS AND METHODS: The data set contains CT and magnetic resonance image scans from 15 patients who underwent cranial radiation therapy. For each patient, pseudo-CTs of the head were generated with a patch-based and a voxel-based algorithm. The accuracy of the pseudo-CTs in comparison to clinical CTs was evaluated by mean absolute error, bias, and the Dice coefficient (of bone). IMRT and VMAT plans were created for each patient. Dose distributions were calculated with both the pseudo-CT and the clinical CT scans and compared by gamma tests, dose-volume histograms, and isocenter doses. RESULTS: The generated pseudo-CTs exhibited average mean absolute errors of 118.7 ± 10.4 HU for the voxel-based algorithm and 73.0 ± 6.4 HU for the patch-based algorithm. The dose calculations were in good agreement and showed gamma test (2 mm, 2%) pass rates for both beam setups (IMRT and VMAT) of over 99% for 14 patients and over 98% for 1 patient. CONCLUSIONS: We showed that the key techniques of our 2 novel algorithms advance the quality of pseudo-CT significantly and generate very competitive pseudo-CTs compared with previously published methods. This quality was confirmed by low dose error in comparison to the ground-truth CT. With the achieved level of accuracy, our patch-based algorithm especially is a candidate for clinical routine use in IMRT and VMAT planning.
EVALuna2:36471

Advances in 4D treatment planning for scanned particle beam therapy - report of dedicated workshops - Bert, Christoph; Graeff, Christian; Riboldi, Marco; Nill, Simeon; Baroni, Guido; Knopf, Antje-Christin (Technology in Cancer Research & Treatment, 2014)
We report on recent progress in the field of mobile tumor treatment with scanned particle beams, as discussed in the latest editions of the 4D treatment planning workshop. The workshop series started in 2009, with about 20 people from 4 research institutes involved, all actively working on particle therapy delivery and development. The first workshop resulted in a summary of recommendations for the treatment of mobile targets, along with a list of requirements to apply these guidelines clinically. The increased interest in the treatment of mobile tumors led to a continuously growing number of attendees: the 2012 edition counted more than 60 participants from 20 institutions and commercial vendors. The focus of research discussions among workshop participants progressively moved from 4D treatment planning to complete 4D treatments, aiming at effective and safe treatment delivery. Current research perspectives on 4D treatments include all critical aspects of time resolved delivery, such as in-room imaging, motion detection, beam application, and quality assurance techniques. This was motivated by the start of first clinical treatments of hepato cellular tumors with a scanned particle beam, relying on gating or abdominal compression for motion mitigation. Up to date research activities emphasize significant efforts in investigating advanced motion mitigation techniques, with a specific interest in the development of dedicated tools for experimental validation. Potential improvements will be made possible in the near future through 4D optimized treatment plans that require upgrades of the currently established therapy control systems for time resolved delivery. But since also these novel optimization techniques rely on the validity of the 4DCT, research focusing on alternative 4D imaging technique, such as MRI based 4DCT generation will continue.
EVALuna2:18197

A Facile One-Pot Synthesis of Water-Soluble, Patchy Fe3O4-Au Nanoparticles for Application in Radiation Therapy - Klein, Stefanie; Hubner, Jakob; Menter, Christina; Distel, Luitpold; Neuhuber, Winfried; Kryschi, Carola (Applied Sciences, 2019)
A facile one-pot synthesis route for the preparation of water-soluble, biocompatible patchy Fe3O4-Au nanoparticles (Fe3O4-Au pNPs) was developed. Biocompatibility was attained through surface functionalization with 1-methyl-3-(dodecylphosphonic acid) imidazolium bromide. The morphology, composition, crystal structure and magnetic properties of the Fe3O4-Au pNPs were investigated by conducting experiments with transmission electron microscopy, energy dispersive X-ray spectroscopy, X-ray diffraction and superconducting quantum interference device, respectively. Internalization of the Fe3O4-Au pNPs by MCF-7 cells occurred via endocytosis. The performance of the Fe3O4-Au pNPs as X-ray radiosensitizer in tumor cells was compared with that of gold nanocluster and Fe3O4 NPs. For this reason, MCF-7, A549 and MCF-10A cells were loaded with the respective kind of nanoparticles and treated with X-rays at doses of 1, 2 or 3 Gy. The nanoparticle-induced changes of the concentration of the reactive oxygen species (ROS) were detected using specific assays, and the cell survival under X-ray exposure was assessed employing the clonogenic assay. In comparison with the gold nanocluster and Fe3O4 NPs, the Fe3O4-Au pNPs exhibited the highest catalytic capacity for ROS generation in MCF-7 and A549 cells, whereas in the X-ray-induced ROS formation in healthy MCF-10A cells was hardly enhanced by the Fe3O4 NPs and Fe3O4-Au pNPs. Moreover, the excellent performance of Fe3O4-Au pNPs as X-ray radiosensitizers was verified by the quickly decaying radiation dose survival curve of the nanoparticle-loaded MCF-7 and A549 cells and corroborated by the small values of the associated dose-modifying factors.
CRIS-Team WoS Importer:2020-02-21

A generic curriculum development model for the biomedical physics component of the educational and training programmes of the non-physics healthcare professions - Caruana, C. J.; Karenauskaite, V.; Mornstein, V.; Vano, E.; Pace, E.; Lammertsma, A. A.; Maas, A. J.J.; Bert, Christoph; Byrne, B.; Colgan, N.; Essers, M.; Isidoro, J.; et al. (Physica Medica, 2021)
The objective of the study was the construction of a generic curriculum development model for the use of biomedical physics (BMP) educators teaching the non-physics healthcare professions (HCP) in Europe. A comprehensive, qualitative cross-sectional Europe-wide survey of the curricula delivered by BMP in Faculties of Medicine and Health Sciences (FMHS) was carried out. Curricular content was collected from faculty web-sites, curricular documents and textbooks. The survey data was supplemented with semi-structured interviews and direct observation during onsite visits. The number of faculties studied was 118 from 67 universities spread all over Europe, whilst the number of onsite visits/interviews was 15 (geographically distributed as follows: Eastern Europe 6, North Western Europe 5, and South Western Europe 4). EU legislation, recommendations by European national medical councils, educational benchmark statements by higher education quality assurance agencies, research journals concerning HCP education and other documents relevant to standards in clinical practice and undergraduate education were also analyzed. Best practices and BMP learning outcomes were elicited from the curricular materials, interviews and documentation and these were subsequently used to construct the curriculum development model. A structured, comprehensive BMP learning outcomes inventory was designed in the format required by the European Qualifications Framework (EQF). The structures of the inventory and curriculum development model make them ideally suited for use by BMP involved in European curriculum development initiatives for the HCP.
CRIS-Team Scopus Importer:2021-05-21
Keywords: Biomedical physics; Curriculum development; Healthcare professions; Medical devices

Aggregated neutrophil extracellular traps limit inflammation by degrading cytokines and chemokines - Schauer, Christine; Janko, Christina; Munoz Becerra, Luis; Zhao, Yi; Kienhöfer, Deborah; Frey, Benjamin; Lell, Michael; Manger, Bernhard; Rech, Juergen; Naschberger, Elisabeth; Holmdahl, Rikard; Krenn, Veit; et al. (Nature Medicine, 2014)
Gout is characterized by an acute inflammatory reaction and the accumulation of neutrophils in response to monosodium urate (MSU) crystals. Inflammation resolves spontaneously within a few days, although MSU crystals can still be detected in the synovial fluid and affected tissues. Here we report that neutrophils recruited to sites of inflammation undergo oxidative burst and form neutrophil extracellular traps (NETs). Under high neutrophil densities, these NETs aggregate and degrade cytokines and chemokines via serine proteases. Tophi, the pathognomonic structures of chronic gout, share characteristics with aggregated NETs, and MSU crystals can induce NETosis and aggregation of NETs. In individuals with impaired NETosis, MSU crystals induce uncontrolled production of inflammatory mediators from neutrophils and persistent inflammation. Furthermore, in models of neutrophilic inflammation, NETosis-deficient mice develop exacerbated and chronic disease that can be reduced by adoptive transfer of aggregated NETs. These findings suggest that aggregated NETs promote the resolution of neutrophilic inflammation by degrading cytokines and chemokines and disrupting neutrophil recruitment and activation.
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Aggressive De-escalation in adjuvant Therapy for HPV-associated Oropharyngeal Cancer. Is Half of Everything enough? - Hecht, Markus; Semrau, Sabine (Strahlentherapie und Onkologie, 2020)
CRIS-Team WoS Importer:2020-04-03

A Kernel-based Framework for Intra-fractional Respiratory Motion Estimation in Radiation Therapy - Geimer, Tobias; Unberath, Mathias; Birlutiu, Adriana; Taubmann, Oliver; Wölfelschneider, Jens; Bert, Christoph; Maier, Andreas (Proceedings of the 2017 IEEE International Symposium on Biomedical Imaging, 2017)
In radiation therapy, tumor tracking allows to adjust the beam such that it follows the respiration-induced tumor motion. However, most clinical approaches rely on implanted fiducial markers to locate the tumor and, thus, only provide sparse information. Motion models have been investigated to estimate dense internal displacement fields from an external surrogate signal, such as range imaging. With increasing surrogate complexity, we propose a respiratory motion estimation framework based on kernel ridge regression to cope with high-dimensional domains. This approach was validated on five patient datasets, consisting of a planning 4DCT and a follow-up 4DCT for each patient. Mean residual error was at best 2.73 ± 0.25 mm, but varied greatly between patients.<br
UnivIS-Import:2017-12-18:Pub.2017.tech.IMMD.IMMD5.akerne_4
Keywords: Motion Models; Range Imaging; Radiation Therapy; Kernel Trick; Active Shape Models

A Kernel Ridge Regression Model for Respiratory Motion Estimation in Radiotherapy - Geimer, Tobias; Birlutiu, Adriana; Unberath, Mathias; Taubmann, Oliver; Bert, Christoph; Maier, Andreas (Bildverarbeitung für die Medizin 2017 - Algorithmen - Systeme - Anwendungen, 2017)
This paper discusses a kernel ridge regression (KRR) model for motion estimation in radiotherapy. Using KRR, dense internal motion fields are estimated from high-dimensional surrogates without the need for prior dimensionality reduction. We compare the proposed model to a related approach with dimensionality reduction in the form of principal component analysis and principle component regression. Evaluation was performed in a simulation study based on nine 4D CT patient data sets achieving a mean estimation error of 0.84 ± 0.21 mm for our approach.<br
UnivIS-Import:2017-12-18:Pub.2017.tech.IMMD.IMMD5.akerne_3

Altered activation of the immune response causes radioresistance in HR-impaired breast cancer cells - Classen, S.; Rahlf, E.; Jungwirth, J.; Poole, L.; Gehre, S.; Rückert, Michael; Petersen, C.; Rothkamm, K.; Gaipl, Udo; Pospiech, H.; Borgmann, K. (RADIOTHERAPY AND ONCOLOGY, 2022)
CRIS-Team WoS Importer:2022-07-22

A Multicenter Evaluation of Different Chemotherapy Regimens in Older Adults With Head and Neck Squamous Cell Carcinoma Undergoing Definitive Chemoradiation - Rühle, Alexander; Weymann, Maria; Behrens, Max; Marschner, Sebastian; Haderlein, Marlen; Fabian, Alexander; Senger, Carolin; Dickstein, Daniel R.; Kraft, Johannes; von der Grün, Jens; Chen, Eric; Aquino-Michaels, Todd; et al. (International Journal of Radiation Oncology Biology Physics, 2024)
Purpose: The number of older adults with head and neck squamous cell carcinoma (HNSCC) is increasing, and treatment of these patients is challenging. Although cisplatin-based chemotherapy concomitantly with radiation therapy is considered the standard regimen for patients with locoregionally advanced HNSCC, there is substantial real-world heterogeneity regarding concomitant chemotherapy in older patients with HNSCC. Methods and Materials: The SENIOR study is an international multicenter cohort study including older patients (≥65 years) with HNSCC treated with definitive radiation therapy at 13 academic centers in the United States and Europe. Patients with concomitant chemoradiation were analyzed regarding overall survival (OS) and progression-free survival (PFS) via Kaplan-Meier analyses. Fine‐Gray competing risk regressions were performed regarding the incidence of locoregional failures and distant metastases. Results: Six hundred ninety-seven patients with a median age of 71 years were included in this analysis. Single-agent cisplatin was the most common chemotherapy regimen (n = 310; 44%), followed by cisplatin plus 5-fluorouracil (n = 137; 20%), carboplatin (n = 73; 10%), and mitomycin C plus 5-fluorouracil (n = 64; 9%). Carboplatin-based regimens were associated with diminished PFS (hazard ratio [HR], 1.39 [1.03-1.89]; P < .05) and a higher incidence of locoregional failures (subdistribution HR, 1.54 [1.00-2.38]; P = .05) compared with single-agent cisplatin, whereas OS (HR, 1.15 [0.80-1.65]; P = .46) was comparable. There were no oncological differences between single-agent and multiagent cisplatin regimens (all P > .05). The median cumulative dose of cisplatin was 180 mg/m2 (IQR, 120-200 mg/m2). Cumulative cisplatin doses ≥200 mg/m2 were associated with increased OS (HR, 0.71 [0.53-0.95]; P = .02), increased PFS (HR, 0.66 [0.51-0.87]; P = .003), and lower incidence of locoregional failures (subdistribution HR, 0.50 [0.31-0.80]; P = .004). Higher cumulative cisplatin doses remained an independent prognostic variable in the multivariate regression analysis for OS (HR, 0.996 [0.993-0.999]; P = .009). Conclusions: Single-agent cisplatin can be considered in the standard chemotherapy regimen for older patients with HNSCC who can tolerate cisplatin. Cumulative cisplatin doses are prognostically relevant in older patients with HNSCC.
CRIS-Team Scopus Importer:2024-01-12

A multi-institution study: comparison of the heating patterns of five different MR-guided deep hyperthermia systems using an anthropomorphic phantom - Curto, Sergio; Mulder, Hendrik Thijmen; Aklan, Bassim; Mils, Oliver; Schmidt, Manfred; Lamprecht, Ulf; Peller, Michael; Wessalowski, Ruediger; Lindner, Lars H.; Fietkau, Rainer; Zips, Daniel; Van Holthe, Netteke; et al. (International Journal of Hyperthermia, 2020)
Introduction: Within the hyperthermia community, consensus exists that clinical outcome of the treatment radiotherapy and/or chemotherapy plus hyperthermia (i.e. elevating tumor temperature to 40 − 44 °C) is related to the applied thermal dose; hence, treatment quality is crucial for the success of prospective multi-institution clinical trials. Currently, applicator quality assurance (QA) measurements are implemented independently at each institution using basic cylindrical phantoms. A multi-institution comparison of heating quality using magnetic resonance thermometry (MRT) and anatomical representative anthropomorphic phantoms provides a unique opportunity to obtain novel QA insights to facilitate multi-institution trial evaluation. Objective: Perform a systematic QA procedure to compare the performance of MR-compatible hyperthermia systems in five institutions. Methods and materials: Anthropomorphic phantoms, including pelvic and spinal bones, were produced. Clinically relevant power of 600 watts was applied for ∼12 min to allow for 8 sequential MR-scans. The 3D-heating distribution, steering capabilities, and presence of off-target heating were analyzed. Results: The evaluated devices show comparable heating profiles for centric and eccentric targets. The differences observed in the 3D-heating profiles are the result of variations in the exact phantom positioning and applicator characteristics, whereby positioning of the phantom followed current ESHO-QA guidelines. Conclusion: Anthropomorphic phantoms were used to perform QA-measurements of MR-guided hyperthermia systems operating in MR-scanners of different brands. Comparable heating profiles are shown for the five evaluated institutions. Subcentimeter differences in position substantially affected the results when evaluating the heating patterns. Integration of advanced phantoms and precise positioning in QA-guidelines should be evaluated to guarantee the best quality patient care.
CRIS-Team Scopus Importer:2020-10-09
Keywords: anthropomorphic phantom; heating patterns; magnetic resonance (MR)-guided hyperthermia; magnetic resonance thermometry (MRT); Quality assurance (QA)

A Multi-Platform Treatment Planning Benchmark Study for Spinal Radiosurgery - Moustakis, C.; Chan, M. K. H.; Kim, J.; Nilsson, J.; Bergman, A.; Bichay, T. J.; Cilla, S.; Deodato, F.; Doro, R.; Eich, H. T. T.; Fau, P.; Fong, M.; et al. (INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 2019)
CRIS-Team WoS Importer:2019-10-01

Analysis of antioxidant Factors in Patients' Blood with chronic Degenerative and inflammatory Diseases in the Course of Low-Dose Radiotherapy - Hehlgans, S.; Donaubauer, Anna-Jasmina; Becker, Ina; Frey, Benjamin; Oppermann, J.; Ott, Oliver; Weissmann, T.; Dilovic, E.; Roedel, C.; Gaipl, Udo; Fournier, C.; Roedel, F. (STRAHLENTHERAPIE UND ONKOLOGIE, 2020)
CRIS-Team WoS Importer:2020-10-02

Analysis of Head and Neck Lymph Node Metastasis Distribution by using Deep Learning automated Lymph Node Level Contouring - Weissmann, Thomas; Huang, Yixing; Speer, Stefan; Semrau, Sabine; Bert, Christoph; Fietkau, Rainer; Putz, Florian (STRAHLENTHERAPIE UND ONKOLOGIE, 2022)
CRIS-Team WoS Importer:2022-06-03

Analysis of the analgesic Effects of LDRT in Patients in the IMMO-LDRT01 Study - Fröhlich, Birgitta; Donaubauer, Anna-Jasmina; Weissmann, T.; Becker, Ina; Ott, Oliver; Fietkau, Rainer; Gaipl, Udo; Frey, Benjamin (STRAHLENTHERAPIE UND ONKOLOGIE, 2020)
CRIS-Team WoS Importer:2020-10-02

Analysis of the Expression of anti-oxidative Factors in the Blood of Patients with chronic degenerative and inflammatory Diseases before and after Low-dose Irradiation - IMMO-LDRT01 Study - Hehlgans, S.; Donaubauer, Anna-Jasmina; Becker, Ina; Frey, Benjamin; Ott, Oliver; Weissmann, Thomas; Fournier, C.; Gaipl, Udo; Roedel, F. (STRAHLENTHERAPIE UND ONKOLOGIE, 2022)
CRIS-Team WoS Importer:2022-06-03

Analysis of the immune status from peripheral whole blood with a single-tube multicolor flow cytometry assay - Donaubauer, Anna-Jasmina; Becker, Ina; Rühle, Paul-Friedrich; Fietkau, Rainer; Gaipl, Udo; Frey, Benjamin (Methods in Enzymology, 2020)
Supplementation of standard cancer therapies (radiotherapy, chemotherapy, surgery) with immunotherapies has revolutionized cancer treatment. In order to include recent improvements of multimodal therapies into clinical routine, knowledge about the immune status, the immune dynamics and the detailed composition and activation of patient's immune system is required. The here presented single-tube multicolor flow cytometry assay allows the discrimination of 20 clinically relevant immune cell subsets and their activation status in peripheral whole blood. It includes 15 different antibodies and can be established on a common 3 laser and 10 color flow-cytometer. Furthermore, this assay is easy to set-up and to perform as well as fast with only 40 min of sample preparation time. Moreover, only 100 μL of whole blood are sufficient for this precise determination of the individual immune status. It is already applied in translational programs of clinical studies and trials and can further be adapted for future ones.
CRIS-Team Scopus Importer:2020-02-04
Keywords: Immune status; Immunophenotyping; Multicolor flow-cytometry; Peripheral whole blood; Radioimmunotherapies

An Analysis of the Use Pattern of Hyperthermia (HT) in Combination with Radio(chemo)therapy or Chemotherapy in European HT Centers - Ademaj, A.; Veltsista, D. P.; Marder, D.; Haelg, R. A.; Puric, E.; Brunner, T. B.; Crezee, H.; Gabrys, D.; Franckena, M.; Gani, C.; Horsman, M. R.; Krempien, R.; et al. (STRAHLENTHERAPIE UND ONKOLOGIE, 2022)
CRIS-Team WoS Importer:2022-06-03

Anatomical accuracy of interactive and automated rigid registration between X-ray CT and FDG-PET - Wolz, Gabriele; Nömayr, Anton; Hothorn, Torsten; Hornegger, Joachim; Römer, Wolfgang; Bautz, Werner; Kuwert, Torsten (Nuklearmedizin-Nuclear Medicine, 2007)
Aim: Comparison of anatomical accuracy of software-based interactive (IRR) and automated rigid registration (ARR) of separately acquired CT and FDG-PET data sets. Patients, methods: Independently acquired PET and helical CT data from 22 tumour patients were registered manually using the Syngo advanced Fusion VC20H tool. IRR was performed separately for the thorax and the abdomen using physiological FDG uptake in several organs as a reference. In addition, ARR was performed with the commercially available software tool Mirada 7D on all of the patients. For both methods, the distances between the representation of 53 malignant lesions on PET and CT were measured in X-, Y-, and Z-direction with reference to a common coordinate system (X-, Y-, Z-distances). Results: The percentage of lesions misregistered by less than 1.5 cm was in X-direction 91% for IRR and 89% for ARR; in Y-direction 85% and 68%; in Z-direction 72% and 51%, respectively. The average X-, Y- and Z-distances for IRR ranged from 0.58 ± 0.55 cm (X-direction) to 1.17 ± 1.66 cm (Z-direction). For ARR, the average X-, Y- and Z-distances varied between 0.66 ± 0.61 cm (X-direction) and 1.81 ± 1.37 cm (Z-direction). Mixed effects analysis of the absolute X-, Y- and Z-distances revealed a significantly better alignment for IRR compared to ARR in Z-direction (p <0.01). Lesion size and localization either in thorax or abdomen had no significant influence on the accuracy of registration. Conclusion: For the majority of malignant lesions, manual image registration with the possibility to separately align different body segments was more accurate than the automated approach. Current software for ARR does not reach the anatomical accuracy reported for PET/CT hybrid scanners. © 2007 Schattauer GmbH.

Anatomical accuracy of lesion localization - Nömayr, Anton; Römer, Wolfgang; Hothorn, Torsten; Pfahlberg, Annette; Hornegger, Joachim; Bautz, Werner; Kuwert, Torsten (Nuklearmedizin-Nuclear Medicine, 2005)

Anatomical accuracy of lesion localization: Retrospective interactive rigid image registration between18F-FDG-PET and X-ray CT - Nömayr, Anton; Römer, Wolfgang; Hothorn, Torsten; Pfahlberg, Annette; Hornegger, Joachim; Bautz, Werner; Kuwert, Torsten (Nuklearmedizin-Nuclear Medicine, 2005)
The aim of this study was to evaluate the anatomical accuracy and reproducibility of retrospective interactive rigid image registration (RIR) between routinely archived X-ray computer tomography (CT) and positron emission tomography performed with F-deoxyglucose (FDG-PET) in oncological patients. Methods: Two observers registered PET and CT data obtained in 37 patients using a commercially available image fusion tool. RIR was performed separately for the thorax and the abdomen using physiological FDG uptake in several organs as a reference. One observer performed the procedure twice (O1a and O1b), another person once (O2). For 94 malignant lesions, clearly visible in CT and PET, the signed and absolute distances between their representation on PET and CT were measured in X-, Y-, and Z-direction with reference to a coordinate system centered in the CT representation of each lesion (X-, Y-, Z-distances). Results: The mean differences of the signed and absolute distances between O1a, O1b, and O2 did not exceed 3 mm in any dimension. The absolute X-, Y-, and Z-distances ranged between 0.57 ± 0.58 cm for O1a (X-direction) and 1.12 ± 1.28 cm for O2 (Z-direction). When averaging the absolute distances measured by O1a, O1b, and O2, the percentage of lesions misregistered by less than 1.5 cm was 91% for the X-, 88% for the Y-, and 77% for the Z-direction. The larger error of fusion determined for the remaining lesions was caused by non-rigid body transformations due to differences in breathing, arm position, or bowel movements between the two examinations. Mixed effects analysis of the signed and absolute X-, Y-, and Z-distances disclosed a significantly greater mis-alignment in the thorax than in the abdomen as well as axially than transaxially. Conclusion: The anatomical inaccuracy of RIR can be expected to be < 1.5 cm for the majority of neoplastic foci. Errors of alignment are bigger in the thorax and in Z-direction, due to non-rigid body transformations caused, e.g., by breathing. © 2005 Schattauer GmbH.

Anatomical Distribution and relative Frequency of Lymph Node Metastases in Prostate Cancer: Creation of a three-dimensional Model of High-risk Regions with potential Implications for the adjuvant Radiotherapy - Filimonova, I.; Fietkau, Rainer; Putz, Florian (STRAHLENTHERAPIE UND ONKOLOGIE, 2019)
CRIS-Team WoS Importer:2019-06-07

An easily expandable multi-drug LC-MS assay for the simultaneous quantification of 57 oral antitumor drugs in human plasma - Kehl, Niklas; Schlichtig, Katja; Dürr, Pauline; Bellut, Laura; Dörje, Frank; Fietkau, Rainer; Pavel, Marianne Ellen; Mackensen, Andreas; Wullich, Bernd; Maas, Renke; Fromm, Martin; Geßner, Arne; et al. (Cancers, 2021)
Oral anticancer drugs have led to significant improvements in the treatment of multiple tumor entities. However, in patients undergoing oral antitumor therapy, plasma concentrations are highly variable, resulting in risks of reduced therapeutic effects or an increase in side effects. One important tool to reduce this variability is therapeutic drug monitoring. In this work we describe a method to simultaneously quantify the plasma concentrations of 57 oral antitumor agents. Quantification of these drugs was achieved using liquid chromatography coupled to an Orbitrap mass spectrometer. The method was fully validated according to the FDA guidelines and constitutes a simple and robust way for exposure monitoring of a wide variety of oral anticancer drugs. Applicability to clinical routine was demonstrated by the analysis of 71 plasma samples taken from 39 patients. In summary, this new multi-drug method allows simultaneous quantification of 57 oral antitumor drugs, which can be applied to exposure monitoring in clinical studies, taking into account the broad variety of oral antitumor drugs prescribed in clinical routine.
CRIS-Team Scopus Importer:2021-12-24
Keywords: Exposure measurement; Kinase inhibitors; Liquid chromatography mass spectrometry; Oral antitumor drug; Orbitrap mass spectrometer

An Investigation of Feature-based Nonrigid Image Registration using Gaussian Process - Bayer, Siming; Spiske, Ute; Geimer, Tobias; Luo, Jie; Wells III, William M.; Ostermeier, Martin; Fahrig, Rebecca; Arya, Nabavi; Bert, Christoph; Eyüpoglu, Ilker Yasin; Maier, Andreas (Algorithmen – Systeme – Anwendungen. Proceedings des Workshops, 2020)
For a wide range of clinical applications, such as adaptive treatment planning or intraoperative image update, feature-based deformable registration (FDR) approaches are widely employed because of their simplicity and low computational complexity. FDR algorithms estimate a dense displacement field by interpolating a sparse field, which is given by the established correspondence between selected features. In this paper, we consider the deformation field as a Gaussian Process (GP), whereas the selected features are regarded as prior information on the valid deformations. Using GP, we are able to estimate the both dense displacement field and a corresponding uncertainty map at once. Furthermore, we evaluated the performance of different hyperparameter settings for squared exponential kernels with synthetic, phantom and clinical data respectively. The quantitative comparison shows, GP-based interpolation has performance on par with state-of-the-art B-spline interpolation. The greatest clinical benefit of GP-based interpolation is that it gives a reliable estimate of the mathematical uncertainty of the calculated dense displacement map.<br

An In Vitro Approach for Investigating the Safety of Lipotransfer after Breast-Conserving Therapy - Promny, Theresa; Kutz, Chiara-Sophia; Jost, Tina; Distel, Luitpold; Kadam, Sheetal; Schmid, Rafael; Arkudas, Andreas; Horch, Raymund E.; Kengelbach-Weigand, Annika (Journal of Personalized Medicine, 2022)
The application of lipotransfer after breast-conserving therapy (BCT) and irradiation in breast cancer patients is an already widespread procedure for reconstructing volume deficits of the diseased breast. Nevertheless, the safety of lipotransfer has still not been clarified yet due to contradictory data. The goal of this in vitro study was to further elucidate the potential effects of lipotransfer on the irradiated remaining breast tissue. The mammary epithelial cell line MCF-10A was co-cultured with the fibroblast cell line MRC-5 and irradiated with 2 and 5 Gy. Afterwards, cells were treated with conditioned medium (CM) from adipose-derived stem cells (ADSC), and the effects on the cellular functions of MCF-10A cells and on gene expression at the mRNA level in MCF-10A and MRC-5 cells were analyzed. Treatment with ADSC CM stimulated transmigration and invasion and decreased the surviving fraction of MCF-10A cells. Further, the expression of cytokines, extracellular, and mesenchymal markers was enhanced in mamary epithelial cells. Only an effect of ADSC CM on irradiated fibroblasts could be observed. The present data suggest epithelial–mesenchymal transition-like changes in the epithelial mammary breast cell line. Thus, the benefits of lipotransfer after BCT should be critically weighed against its possible risks for the affected patients.<br

Announcement of the scientific Awards to be awarded in 2020 - Bert, Christoph (Zeitschrift für Medizinische Physik, 2019)
EVALuna2:213673

A novel concept for CT with fixed anodes (FACT): Medical imaging based on the feasibility of thermal load capacity - Kellermeier, Markus; Bert, Christoph; Müller, Reinhold (Physica Medica, 2015)
Focussing primarily on thermal load capacity, we describe the performance of a novel fixed anode CT (FACT) compared with a 100 kW reference CT. Being a fixed system, FACT has no focal spot blurring of the X-ray source during projection. Monte Carlo and finite element methods were used to determine the fluence proportional to thermal capacity. Studies of repeated short-time exposures showed that FACT could operate in pulsed mode for an unlimited period. A virtual model for FACT was constructed to analyse various temporal sequences for the X-ray source ring, representing a circular array of 1160 fixed anodes in the gantry. Assuming similar detector properties at a very small integration time, image quality was investigated using an image reconstruction library. Our model showed that approximately 60 gantry rounds per second, i.e. 60 sequential targetings of the 1160 anodes per second, were required to achieve a performance level equivalent to that of the reference CT (relative performance, RP = 1) at equivalent image quality. The optimal projection duration in each direction was about 10 ?s. With a beam pause of 1 ?s between projections, 78.4 gantry rounds per second with consecutive source activity were thermally possible at a given thermal focal spot. The settings allowed for a 1.3-fold (RP = 1.3) shorter scan time than conventional CT while maintaining radiation exposure and image quality. Based on the high number of rounds, FACT supports a high image frame rate at low doses, which would be beneficial in a wide range of diagnostic and technical applications.
EVALuna2:18269

A novel HSP90 inhibitor with reduced hepatotoxicity synergizes with radiotherapy to induce apoptosis, abrogate clonogenic survival, and improve tumor control in models of colorectal cancer - Kinzel, Linda; Ernst, Anne; Orth, Michael; Albrecht, Valerie; Hennel, Roman; Brix, Nikko; Frey, Benjamin; Gaipl, Udo; Zuchtriegel, Gabriele; Reichel, Christoph A.; Blutke, Andreas; Schilling, Daniela; et al. (Oncotarget, 2016)
The chaperone heat shock protein 90 (HSP90) crucially supports the maturation, folding, and stability of a variety of client proteins which are of pivotal importance for the survival and proliferation of cancer cells. Consequently, targeting of HSP90 has emerged as an attractive strategy of anti-cancer therapy, and it appears to be particularly effective in the context of molecular sensitization towards radiotherapy as has been proven in preclinical models of different cancer entities. However, so far the clinical translation has largely been hampered by suboptimal pharmacological properties and serious hepatotoxicity of first- and second-generation HSP90 inhibitors. Here, we report on NW457, a novel radicicol-derived member of the pochoxime family with reduced hepatotoxicity, how it inhibits the DNA damage response and how it synergizes with ionizing irradiation to induce apoptosis, abrogate clonogenic survival, and improve tumor control in models of colorectal cancer in vitro and in vivo.
EVALuna2:32934

Anti-inflammatory effects of an autologous gold-based serum therapy in osteoarthritis patients - Feldt, Jessica; Donaubauer, Anna-Jasmina; Welss, Jessica; Schneider, Ulrich; Gaipl, Udo; Paulsen, Friedrich (Scientific Reports, 2022)
Osteoarthritis (OA) involves activation and recruitment of immune cells to affected joints, including the production of pro-inflammatory cytokines. Here, a gold-based autologous serum therapy is investigated for its effect on peripheral blood cell composition and cytokine levels in OA patients. From six OA patients serum and blood samples were collected before and after second therapy treatment for analysis of peripheral blood cell composition as well as cytokine levels compared to control samples. This therapy significantly downregulates CD4+ T cells and B cells in OA patients after second treatment compared to healthy controls. Monocytes are significantly upregulated in patients after second treatment Serum IL-9 and TNF-α levels are downregulated in patients after second treatment compared to healthy control serum. The activation status of immune cells was modulated after therapy in patients. Anti-inflammatory effects of the peripheral blood cell composition in OA patients can be seen after therapy treatment. After two treatments IL-9 and TNF-α are significantly downregulated in patient serum. Here, primary data of a new autologous therapy for OA treatment and its modulatory effects on cytokines are presented.
CRIS-Team Scopus Importer:2022-03-11

Antiseizure medication and perceived “fair” cost allocation: A factorial survey among neurologists, persons with epilepsy, their relatives, and a control group - Stritzelberger, Jenny; Walther, Katrin; Olmes, David; Gollwitzer, Stefanie; Graf, Wolfgang; Welte, Tamara; Lang, Johannes; Reindl, Caroline; Schwab, Stefan; Kriwy, Peter; Hamer, Hajo (Epilepsia, 2022)
Objective: Because resources are limited in modern health care systems, the decision on the allocation of expensive drugs can be supported by a public consent. This study examines how various factors influence subjectively perceived “fair” pricing of antiseizure medication (ASM) among four groups including physicians, persons with epilepsy (PWEs), their relatives, and a control group. Methods: We conducted a factorial survey. Vignettes featured a fictional PWE receiving a fictional ASM. The characteristics of the fictional PWE, ASM, and epilepsy varied. Participants were asked to assess the subjectively appropriate annual cost of ASM treatment per year for each scenario. Results: Fifty-seven PWEs (mean age (SD) 37.7 ± 12.3, 45.6% female), 44 relatives (age 48.4 ± 15.7, 51.1% female), 46 neurologists (age 37.1 ± 9.6, 65.2% female), and 47 persons in the control group (age 31.2 ± 11.2, 68.1% female) completed the questionnaire. The amount of money that respondents were willing to spend for ASM treatment was higher than currently needed in Germany and increased with disease severity among all groups. All groups except for PWEs accepted higher costs of a drug with better seizure control. Physicians and the control group, but not PWEs and their relatives, tended to do so also for minor or no side effects. Physicians reduced the costs for unemployed patients and the control group spent less money for older patients. Significance: ASM effectiveness appears to justify higher costs. However, the control group attributed less money to older PWEs and physicians allocated fewer drug costs to unemployed PWEs.
CRIS-Team Scopus Importer:2022-08-19

Antitumor immune responses induced by ionizing irradiation and further immune stimulation - Frey, Benjamin; Rubner, Yvonne; Kulzer, Lorenz; Werthmöller, Nina; Weiss, Eva-Maria; Fietkau, Rainer; Gaipl, Udo (Cancer Immunology Immunotherapy, 2014)
The therapy of cancer emerged as multimodal treatment strategy. The major mode of action of locally applied radiotherapy (RT) is the induction of DNA damage that triggers a network of events that finally leads to tumor cell cycle arrest and cell death. Along with this, RT modifies the phenotype of the tumor cells and their microenvironment. Either may contribute to the induction of specific and systemic antitumor immune responses. The latter are boosted when additional immune therapy (IT) is applied at distinct time points during RT. We will focus on therapy-induced necrotic tumor cell death that is immunogenic due to the release of damage-associated molecular patterns. Immune-mediated distant bystander (abscopal) effects of RT when combined with dendritic cell-based IT and the role of fractionation of radiation in the induction of immunogenic tumor cell death will be discussed. Autologous whole-tumor-cell-based vaccines generated by high hydrostatic pressure technology will be introduced and the influence of cytokines and the immune modulator AnnexinA5 on the ex vivo generated or in situ therapy-induced vaccine efficacy will be outlined. RT should be regarded as immune adjuvant for metastatic disease and as a tool for the generation of an in situ vaccine when applied at distinct fractionation doses or especially in combination with IT to generate immune memory against the tumor. To identify the most beneficial combination and chronology of RT with IT is presumably one of the biggest challenges of innovative tumor research and therapies.
EVALuna2:18146

Anti-tumor immune responses in primary and abscopal tumors differently depend on radiotherapy fractionation and immunotherapy modalities - Rueckert, M.; Frey, Benjamin; Fietkau, Rainer; Gaipl, Udo (2018)
EVALuna2:36507

A patterns of care analysis of hyperthermia in combination with radio(chemo)therapy or chemotherapy in European clinical centers - Ademaj, Adela; Veltsista, Paraskevi D.; Marder, Dietmar; Haelg, Roger A.; Puric, Emsad; Brunner, Thomas B.; Crezee, Hans; Gabrys, Dorota; Franckena, Martine; Gani, Cihan; Horsman, Michael R.; Krempien, Robert; et al. (Strahlentherapie und Onkologie, 2022)
Purpose The combination of hyperthermia (HT) with radio(chemo)therapy or chemotherapy (CT) is an established treatment strategy for specific indications. Its application in routine clinical practice in Europe depends on regulatory and local conditions. We conducted a survey among European clinical centers to determine current practice of HT. Methods A questionnaire with 22 questions was sent to 24 European HT centers. The questions were divided into two main categories. The first category assessed how many patients are treated with HT in combination with radio(chemo)therapy or CT for specific indications per year. The second category addressed which hyperthermia parameters are recorded. Analysis was performed using descriptive methods. Results The response rate was 71% (17/24) and 16 centers were included in this evaluation. Annually, these 16 centers treat approximately 637 patients using HT in combination with radio(chemo)therapy or CT. On average, 34% (range: 3-100%) of patients are treated in clinical study protocols. Temperature readings and the time interval between HT and radio(chemo)therapy or CT are recorded in 13 (81%) and 9 (56%) centers, respectively. The thermal dose quality parameter "cumulative equivalent minutes at 43 degrees C" (CEM43 degrees C) is only evaluated in five (31%) centers for each HT session. With regard to treatment sequence, 8 (50%) centers administer HT before radio(chemo)therapy and the other 8 in the reverse order. Conclusion There is a significant heterogeneity among European HT centers as to the indications treated and the recording of thermometric parameters. More evidence from clinical studies is necessary to achieve standardization of HT practice.
CRIS-Team WoS Importer:2022-09-09

A phase 1b randomised, placebo-controlled trial of nabiximols cannabinoid oromucosal spray with temozolomide in patients with recurrent glioblastoma - Twelves, Chris; Sabel, Michael; Checketts, Daniel; Miller, Sharon; Tayo, Bola; Jove, Maria; Brazil, Lucy; Short, Susan C.; McBain, Catherine; Haylock, Brian; Mulholland, Paul; Herbert, Christopher; et al. (British Journal of Cancer, 2021)
Background: Preclinical data suggest some cannabinoids may exert antitumour effects against glioblastoma (GBM). Safety and preliminary efficacy of nabiximols oromucosal cannabinoid spray plus dose-intense temozolomide (DIT) was evaluated in patients with first recurrence of GBM. Methods: Part 1 was open-label and Part 2 was randomised, double-blind, and placebo-controlled. Both required individualised dose escalation. Patients received nabiximols (Part 1, n = 6; Part 2, n = 12) or placebo (Part 2 only, n = 9); maximum of 12 sprays/day with DIT for up to 12 months. Safety, efficacy, and temozolomide (TMZ) pharmacokinetics (PK) were monitored. Results: The most common treatment-emergent adverse events (TEAEs; both parts) were vomiting, dizziness, fatigue, nausea and headache. Most patients experienced TEAEs that were grade 2 or 3 (CTCAE). In Part 2, 33% of both nabiximols- and placebo-treated patients were progression-free at 6 months. Survival at 1 year was 83% for nabiximols- and 44% for placebo-treated patients (p = 0.042), although two patients died within the first 40 days of enrolment in the placebo arm. There were no apparent effects of nabiximols on TMZ PK. Conclusions: With personalised dosing, nabiximols had acceptable safety and tolerability with no drug–drug interaction identified. The observed survival differences support further exploration in an adequately powered randomised controlled trial. Clinical trial registration: ClinicalTrials.gov: Part 1– NCT01812603; Part 2– NCT01812616.
CRIS-Team Scopus Importer:2021-03-05

Apoptotic cell clearance and its role in the origin and resolution of chronic inflammation - Munoz, Luis Enrique; Berens, Christian; Lauber, Kirsten; Gaipl, Udo; Herrmann, Martin (Frontiers in Immunology, 2015)
EVALuna2:13110

APPA-HEALTH-21 Low doses of ionizing radiation reduce osteoclast numbers and increase osteoblast mineralization - Deloch, Lisa; Cucu, Aljona; Frey, Benjamin; Fournier, Claudia; Gaipl, Udo (2016)

APPA-HEALTH-28 The influence of ionizing radiation on differentiation and function of osteoclasts - Deloch, Lisa; Cucu, Aljona; Hoengl, N; Frey, Benjamin; Kraft, Daniela; Durante, Marco; Gaipl, Udo; Fournier, Claudia (2015)

App for the Early Detection of Side Effects of Immunotherapy - Goldbrunner, L.; Hecht, Markus; Fietkau, Rainer; Distel, Luitpold (STRAHLENTHERAPIE UND ONKOLOGIE, 2021)
CRIS-Team WoS Importer:2021-07-16

Appreciation for Prof. Rolf Sauer on the occasion of the transferral of the editorship of "Strahlentherapie und Onkologie" - Fietkau, Rainer; Wenz, Frederik (Strahlentherapie und Onkologie, 2015)
EVALuna2:18268

A Prospective Real-World Multi-Center Study to Evaluate Progression-Free and Overall Survival of Radiotherapy with Cetuximab and Platinum-Based Chemotherapy with Cetuximab in Locally Recurrent Head and Neck Cancer - Hecht, Markus; Hahn, Dennis; Wolber, Philipp; Hautmann, Matthias G.; Reichert, Dietmar; Weniger, Steffi; Belka, Claus; Bergmann, Tobias; Goehler, Thomas; Welslau, Manfred; Gross-Thie, Christina; Guntinas-Lichius, Orlando; et al. (Cancers, 2021)
Simple Summary Despite recent developments in immune checkpoint inhibitors, the treatment of locoregionally recurrent head and neck squamous cell cancer (HNSCC) remains challenging. Prospective data comparing re-irradiation with systemic treatment are not available. The SOCCER trial represents a prospective non-interventional multicenter trial that enrolled patients with locoregionally recurrent HNSCC treated with cetuximab in combination with re-radiotherapy or chemotherapy. A total of 192 patients were analyzed. Radiotherapy combined with cetuximab had superior progression-free and overall survival compared to chemotherapy with cetuximab. This highlights the high efficacy of local re-radiotherapy in combination with cetuximab in patients with locoregionally recurrent HNSCC. Treatment options of locoregional recurrent head and neck squamous cell cancer (HNSCC) include both local strategies as surgery or re-radiotherapy and systemic therapy. In this prospective, multi-center, non-interventional study, patients were treated either with platinum-based chemotherapy and cetuximab (CT + Cet) or re-radiotherapy and cetuximab (RT + Cet). In the current analysis, progression-free survival (PFS) and overall survival (OS) were compared in patients with locoregional recurrence. Four hundred seventy patients were registered in 97 German centers. After exclusion of patients with distant metastases, a cohort of 192 patients was analyzed (129 CT + Cet, 63 RT + Cet). Radiotherapy was delivered as re-irradiation to 70% of the patients. The mean radiation dose was 51.8 Gy, whereas a radiation dose of >= 60 Gy was delivered in 33% of the patients. Chemotherapy mainly consisted of cisplatin/5-flurouracil (40%) or carboplatin/5-flurouracil (29%). The median PFS was 9.2 months in the RT + Cet group versus 5.1 months in the CT + Cet group (hazard ratio for disease progression or death, 0.40, 95% CI, 0.27-0.57, p < 0.0001). Median OS was 12.8 months in the RT + Cet group versus 7.9 months in the CT + Cet group (hazard ratio for death, 0.50, 95% CI, 0.33-0.75, p = 0.0008). In conclusion, radiotherapy combined with cetuximab improved survival compared to chemotherapy combined with cetuximab in locally recurrent HNSCC.
CRIS-Team WoS Importer:2021-08-06

A prospective study on histone ?-H2AX and 53BP1 foci expression in rectal carcinoma patients: correlation with radiation therapy-induced outcome - Djuzenova, Cholpon S.; Zimmermann, Marcus; Katzer, Astrid; Fiedler, Vanessa; Distel, Luitpold; Gasser, Martin; Waaga-Gasser, Anna-Maria; Flentje, Michael; Polat, Buelent (BMC Cancer, 2015)
The prognostic value of histone ?-H2AX and 53BP1 proteins to predict the radiotherapy (RT) outcome of patients with rectal carcinoma (RC) was evaluated in a prospective study. High expression of the constitutive histone ?-H2AX is indicative of defective DNA repair pathway and/or genomic instability, whereas 53BP1 (p53-binding protein 1) is a conserved checkpoint protein with properties of a DNA double-strand breaks sensor.Using fluorescence microscopy, we assessed spontaneous and radiation-induced foci of ?-H2AX and 53BP1 in peripheral blood mononuclear cells derived from unselected RC patients (n = 53) undergoing neoadjuvant chemo- and RT. Cells from apparently healthy donors (n = 12) served as references.The ?-H2AX assay of in vitro irradiated lymphocytes revealed significantly higher degree of DNA damage in the group of unselected RC patients with respect to the background, initial (0.5 Gy, 30 min) and residual (0.5 Gy and 2 Gy, 24 h post-radiation) damage compared to the control group. Likewise, the numbers of 53BP1 foci analyzed in the samples from 46 RC patients were significantly higher than in controls except for the background DNA damage. However, both markers were not able to predict tumor stage, gastrointestinal toxicity or tumor regression after curative RT. Interestingly, the mean baseline and induced DNA damage was found to be lower in the group of RC patients with tumor stage IV (n = 7) as compared with the stage III (n = 35). The difference, however, did not reach statistical significance, apparently, because of the limited number of patients.The study shows higher expression of ?-H2AX and 53BP1 foci in rectal cancer patients compared with healthy individuals. Yet the data in vitro were not predictive in regard to the radiotherapy outcome.
EVALuna2:18321

APTES-Terminated ultrasmall and iron-doped silicon nanoparticles as X-Ray dose enhancer for radiation therapy - Klein, Stefanie; Wegmann, Marc; Distel, Luitpold; Neuhuber, Winfried; Kryschi, Carola (Biochemical and Biophysical Research Communications, 2018)
Silicon nanoparticles with sizes between were synthesized through wet-chemistry procedures using diverse phase transfer reagents. On the other hand, the preparation of iron-doped silicon nanoparticles was carried out using the precursor Na4Si4 containing 5% Fe. Biocompatibility of all silicon nanoparticle samples was achieved by surface-stabilizing with (3-aminopropyl)triethoxysilane. These surface structures provided positive surface charges which facilitated electrostatic binding to the negatively charged biological membranes. The mode of interaction with membranes, being either incorporation or just attachment, was found to depend on the nanoparticle size. The smallest silicon nanoparticles (ca. 1.5 nm) were embedded in the mitochondrial membrane in MCF-7 cells. When interacting with X-rays these silicon nanoparticles were observed to enhance the superoxide formation upon depolarizing the mitochondrial membrane. X-ray irradiation of MCF-7 cells loaded with the larger silicon nanoparticles was shown to increase the intracellular singlet oxygen generation. The doping of the silicon nanoparticles with iron led to additional production of hydroxyl radicals via the Fenton reaction.
EVALuna2:35202

A semi-automatic Segmentation Pipeline for sequential Volumetric Analysis of intracranial Tumors - Putz, Florian; Knippen, S.; Fietkau, Rainer (2017)
EVALuna2:32900

Assessing Organ-at-risk Auto-contouring Solutions: Which Metrics are most predictive of clinical Time Savings? - Putz, Florian; Huang, Yixing; Weissmann, Thomas; Mansoorian, Sina; Lamrani, Allison; Sommer, P.; Fischer, S.; Srinivasan, A.; Frey, Benjamin; Gaipl, Udo; Ott, Oliver; Fietkau, Rainer; et al. (STRAHLENTHERAPIE UND ONKOLOGIE, 2022)
CRIS-Team WoS Importer:2022-06-03

Assessment of segmentation dependence in macroscopic lung cavity extraction - Khdeir, Asmaa; Geimer, Tobias; Chen, Shuqing; Goppert, Eric; Dankbar, Maximilian; Bert, Christoph; Maier, Andreas (Informatik aktuell, 2018)
Training of respiratory motion models and population-based patient phantoms of the lung often requires the definition of the entire lung cavity region in the 4D-CT. To ease the workload of clinical experts, automatic selection is highly desirable. Many lung cavity extraction methods rely on a pre-segmented lung volume.
CRIS-Team Scopus Importer:2022-06-05

Assessment of the implant geometry in fractionated interstitial HDR breast brachytherapy using an electromagnetic tracking system - Kellermeier, Markus; Fietkau, Rainer; Strnad, Vratislav; Bert, Christoph (Brachytherapy, 2018)
PURPOSE: During the partial-breast treatment course by interstitial brachytherapy, electromagnetic tracking (EMT) was applied to measure the implant geometry. Implant-geometry variation, choice of reference data, and three registration methods were assessed. METHODS AND MATERIALS: The implant geometry was measured in 28 patients after catheter implantation (EMTbed), during CT imaging (EMTCT), and in each of up to n = 9 treatment fractions (EMTF(k), k = 1, 2,… n). EMTF(k) were registered to the planned implant reconstruction (CTplan) by using all dwell positions (DPs), the button centers, or three fiducial sensors on the patient's skin. Variation in implant geometry obtained from EMTF(k) was assessed for EMTbed, EMTCT, and CTplan. RESULTS: EMT was used to measure 3932 catheters. A duration of 6.5 ± 1.7 min was needed for each implant measurement (mean, 17 catheters) plus setup of the EMT system. Data registration based on the DP deviated significantly lower than registration on button centers or fiducial sensors. Within a registration group, there was a <0.5-mm difference in the choice of reference data. Using CTplan as reference for registration, the mean residual distance of DPs on EMT-derived DPs was found at 2.1 ± 1.6 mm (EMTbed), 1.3 ± 0.9 mm (EMTCT), and 2.5 ± 1.5 mm (EMTF(k)). CONCLUSIONS: EMT can assess the implant geometry in high-dose-rate interstitial brachytherapy breast treatments. EMTbed, EMTCT, and CTplan data can serve as reference for assessment of implant changes.
EVALuna2:36444

Association of Plane of Total Mesorectal Excision With Prognosis of Rectal Cancer: Secondary Analysis of the CAO/ARO/AIO-04 Phase 3 Randomized Clinical Trial - Kitz, Julia; Fokas, Emmanouil; Beissbarth, Tim; Stroebel, Philipp; Wittekind, Christian; Hartmann, Arndt; Rueschoff, Josef; Papadopoulos, Thomas; Roesler, Elisabeth; Ortloff-Kittredge, Peter; Kania, Ulrich; Schlitt, Hans; et al. (JAMA Surgery, 2018)
Importance: Previous retrospective studies have shown that surgical quality affects local control in rectal cancer.. Objective: In this secondary end point analysis, we evaluated the prognostic effect of the total mesorectal excision (TME) plane in the CAO/ARO/AIO-04 phase 3 randomized clinical trial. Design, Setting, and Participants: The CAO/ARO/AIO-04 trial enrolled 1236 patients with cT3-4 and/or node-positive rectal adenocarcinoma from 88 centers in Germany between July 25, 2006, and February 26, 2010. Interventions: Patients were randomized to receive treatment with standard fluorouracil-based preoperative chemoradiotherapy (CRT) alone (control arm) or oxaliplatin (experimental arm) followed by TME and adjuvant chemotherapy. Main Outcomes and Measures: The TME quality (mesorectal, intramesorectal, and muscularis propria plane) was prospectively assessed in 1152 operation specimens. An assessment was performed independently by pathologists and surgeons. The results were correlated with clinicopathologic data and the clinical outcome was tested, including multivariable analysis with the Cox regression model. Results: Of 1152 German Caucasian participants, 332 (28.8) were women and the mean age was 63 years. The plane of TME was mesorectal in 930 patients (80.7%), intramesorectal in 169 (14.7%), and muscularis propria in 53 (4.6%). In a univariable analysis, the TME plane was significantly associated with 3-year disease-free survival (mesorectal vs intramesorectal vs muscularis propria, 95% CI, 73.1-78.8 vs 61.6-76.0 vs 55.6-81.3, respectively; P = .01), cumulative incidence of local and distant recurrences (mesorectal vs intramesorectal vs muscularis propria, 95% CI, 2.0-4.5 vs 1.2-8.1 vs 2.5-20.5, respectively; P < .001; and mesorectal vs intramesorectal vs muscularis propria, 95% CI, 17.0-22.4 vs 18.3-32.0 vs 14.2-39.0, respectively; P = .03, respectively), and overall survival (mesorectal vs intramesorectal vs muscularis propria, 95% CI, 88.3-92.3 vs 79.7-91.0 vs 81.6-98.7, respectively; P = .02). In contrast to the pathologist-based evaluation, the assessment of TME plane by the operating surgeon failed to demonstrate prognostic significance for any of these clinical end points. In a multivariable analysis, the plane of surgery (mesorectal vs muscularis propria TME) constituted an independent factor for local recurrence (P = .002). Conclusions and Relevance: This phase 3 randomized clinical trial confirms the long-term clinical effect of TME plane quality on local recurrence, as initially reported in the MRC CR07 study. The data highlight the key role of pathologists and surgeons in the multidisciplinary management of rectal cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT00349076.
EVALuna2:34814

A tool to automatically analyze electromagnetic tracking data from high dose rate brachytherapy of breast cancer patients - Goetz, Th. I.; Lahmer, Godehard; Strnad, Vratislav; Bert, Christoph; Hensel, Bernhard; Tome, A. M.; Lang, E. W. (PLoS ONE, 2017)
During High Dose Rate Brachytherapy (HDR-BT) the spatial position of the radiation source inside catheters implanted into a female breast is determined via electromagnetic tracking (EMT). Dwell positions and dwell times of the radiation source are established, relative to the patient's anatomy, from an initial X-ray-CT-image. During the irradiation treatment, catheter displacements can occur due to patient movements. The current study develops an automatic analysis tool of EMT data sets recorded with a solenoid sensor to assure concordance of the source movement with the treatment plan. The tool combines machine learning techniques such as multi-dimensional scaling (MDS), ensemble empirical mode decomposition (EEMD), singular spectrum analysis (SSA) and particle filter (PF) to precisely detect and quantify any mismatch between the treatment plan and actual EMT measurements. We demonstrate that movement artifacts as well as technical signal distortions can be removed automatically and reliably, resulting in artifact-free reconstructed signals. This is a prerequisite for a highly accurate determination of any deviations of dwell positions from the treatment plan.
EVALuna2:33034

Atrioventricular node ablation in Langendorff-perfused porcine hearts using carbon ion particle therapy: methods and an in vivo feasibility investigation for catheter-free ablation of cardiac arrhythmias - Lehmann, H. Immo; Richter, Daniel; Prokesch, Hannah; Graeff, Christian; Prall, Matthias; Simoniello, Palma; Fournier, Claudia; Bauer, Julia; Kaderka, Robert; Weymann, Alexander; Szabó, Gábor; Sonnenberg, Karin; et al. (Circulation-Arrhythmia and Electrophysiology, 2015)
Particle therapy, with heavy ions such as carbon-12 ((12)C), delivered to arrhythmogenic locations of the heart could be a promising new means for catheter-free ablation. As a first investigation, we tested the feasibility of in vivo atrioventricular node ablation, in Langendorff-perfused porcine hearts, using a scanned 12C beam.Intact hearts were explanted from 4 (30-40 kg) pigs and were perfused in a Langendorff organ bath. Computed tomographic scans (1 mm voxel and slice spacing) were acquired and (12)C ion beam treatment planning (optimal accelerator energies, beam positions, and particle numbers) for atrioventricular node ablation was conducted. Orthogonal x-rays with matching of 4 implanted clips were used for positioning. Ten Gray treatment plans were repeatedly administered, using pencil beam scanning. After delivery, positron emission tomography-computed tomographic scans for detection of ?(+) ((11)C) activity were obtained. A (12)C beam with a full width at half maximum of 10 mm was delivered to the atrioventricular node. Delivery of 130 Gy caused disturbance of atrioventricular conduction with transition into complete heart block after 160 Gy. Positron emission computed tomography demonstrated dose delivery into the intended area. Application did not induce arrhythmias. Macroscopic inspection did not reveal damage to myocardium. Immunostaining revealed strong ?H2AX signals in the target region, whereas no ?H2AX signals were detected in the unirradiated control heart.This is the first report of the application of a (12)C beam for ablation of cardiac tissue to treat arrhythmias. Catheter-free ablation using 12C beams is feasible and merits exploration in intact animal studies as an energy source for arrhythmia elimination.
EVALuna2:18308

Attenuation-based automatic kilovolt (kV)-selection in computedtomography of the chest: Effects on radiation exposure and imagequality - Eller, Achim; Wüst, Wolfgang; Scharf, Michael; Brand, Michael; Achenbach, Stephan; Uder, Michael; Lell, Michael (European Journal of Radiology, 2013)
Objectives: To evaluate an automated attenuation-based kV-selection in computed tomography of thechest in respect to radiation dose and image quality, compared to a standard 120 kV protocol.Materials and methods: 104 patients were examined using a 128-slice scanner. Fifty examinations (58 ± 15years, study group) were performed using the automated adaption of tube potential (100-140 kV), basedon the attenuation profile of the scout scan, 54 examinations (62 ± 14 years, control group) with fixed120 kV. Estimated CT dose index (CTDI) of the software-proposed setting was compared with a 120 kVprotocol. After the scan CTDI volume (CTDIvol) and dose length product (DLP) were recorded. Imagequality was assessed by region of interest (ROI) measurements, subjective image quality by two observerswith a 4-point scale (3 - excellent, 0 - not diagnostic).Results: The algorithm selected 100 kV in 78% and 120 kV in 22%. Overall CTDIvol reduction was 26.6%(34% in 100 kV) overall DLP reduction was 22.8% (32.1% in 100 kV) (all p < 0.001). Subjective image qualitywas excellent in both groups.Conclusion: The attenuation based kV-selection algorithm enables relevant dose reduction (?27%) inchest-CT while keeping image quality parameters at high levels. © 2013 Elsevier Ireland Ltd. All rights reserved.
CRIS-Team Scopus Importer:2023-03-08
Keywords: Chest; Computed tomography; Dose reduction; Tube potentialImage quality

Auswirkungen der Kombination des Ligase IV Inhibitors SCR7 mit ionisierender Strahlung auf HNO-Tumorzelllinien und Normalgewebszellen - Hildebrand, Laura; Jost, Tina; Hecht, Markus; Fietkau, Rainer; Distel, Luitpold (STRAHLENTHERAPIE UND ONKOLOGIE, 2022)
CRIS-Team WoS Importer:2022-06-03

Autologous whole tumor cell-based vaccines generated with high hydrostatic pressure bear immunogenic potential and act synergistically with radiotherapy to retard tumor growth - Frey, Benjamin; Seitz, C.; Weiss, E. M.; Rueckert, M.; Schlücker, Eberhard; Schaft, Niels; Fietkau, Rainer; Gaipl, Udo (2017)
EVALuna2:32864

Automated data processing and BigData in radiation therapy - Schmidt, O.; Ballmann, N.; Bert, Christoph; Fietkau, Rainer (RADIOTHERAPY AND ONCOLOGY, 2019)
CRIS-Team WoS Importer:2019-06-18

Automated Semi-Quantitative Analysis of Breast MRI: Potential Imaging Biomarker for the Prediction of Tissue Response to Neoadjuvant Chemotherapy - Dietzel, Matthias; Kaiser, Clemens; Pinker, Katja; Wenkel, Evelyn; Hammon, Matthias; Uder, Michael; Baiti, Barbara Bennani; Clauser, Paola; Schulz-Wendtland, Rüdiger; Baltzer, Pascal (Breast Care, 2017)
We aimed to investigate an automated semi-quantitative software as an imaging biomarker for the prediction of tissue response (TR) after completion of neoadjuvant chemotherapy (NAC).Breast magnetic resonance imaging (MRI) (1.5T, protocol according to international recommendations) of 67 patients with biopsy-proven invasive breast cancer were examined before and after NAC. After completion of NAC, histopathologic assessments of TR were classified according to the Chevallier grading system (CG1/4: full/non-responder; CG2/C3: partial responder). A commercially available fully automatic software (CADstream) extracted MRI parameters of tumor extension (tumor diameter/volume: TD/TV). Pre- versus post-NAC values were compared (?TV and ?TD). Additionally, the software performed volumetric analyses of vascularization (VAV) after NAC. Accuracy of MRI parameters to predict TR were identified (cross-tabs, ROC, AUC, Kruskal-Wallis).There were 37 (34.3%) CG1, 7 (6.5%) CG2, 53 (49.1%) CG3, and 11 (10.2%) CG4 lesions. The software reached area under the curve levels of 79.5% (CG1/complete response: ?TD), 68.6% (CG2, CG3/partial response: VAV), and 88.8% to predict TR (CG4/non-response: ?TV).Semi-quantitative automated analysis of breast MRI data enabled the prediction of tissue response to NAC.
EVALuna2:14712

Automated tube voltage adaptation in head and neck computed tomography between 120 and 100 kV: effects on image quality and radiation dose - May, Matthias; Kramer, Manuel; Eller, Achim; Wüst, Wolfgang; Scharf, Michael; Brand, Michael; Saake, Marc; Schmidt, Bernhard; Uder, Michael; Lell, Michael (Neuroradiology, 2014)
Low tube voltage allows for computed tomography (CT) imaging with increased iodine contrast at reduced radiation dose. We sought to evaluate the image quality and potential dose reduction using a combination of attenuation based tube current modulation (TCM) and automated tube voltage adaptation (TVA) between 100 and 120 kV in CT of the head and neck.One hundred thirty consecutive patients with indication for head and neck CT were examined with a 128-slice system capable of TCM and TVA. Reference protocol was set at 120 kV. Tube voltage was reduced to 100 kV whenever proposed by automated analysis of the localizer. An additional small scan aligned to the jaw was performed at a fixed 120 kV setting. Image quality was assessed by two radiologists on a standardized Likert-scale and measurements of signal- (SNR) and contrast-to-noise ratio (CNR). Radiation dose was assessed as CTDIvol.Diagnostic image quality was excellent in both groups and did not differ significantly (p = 0.34). Image noise in the 100 kV data was increased and SNR decreased (17.8/9.6) in the jugular veins and the sternocleidomastoid muscle when compared to 120 kV (SNR 24.4/10.3), but not in fatty tissue and air. However, CNR did not differ statistically significant between 100 (23.5/14.4/9.4) and 120 kV data (24.2/15.3/8.6) while radiation dose was decreased by 7-8%.TVA between 100 and 120 kV in combination with TCM led to a radiation dose reduction compared to TCM alone, while keeping CNR constant though maintaining diagnostic image quality.
EVALuna2:14375

Automated tube voltage selection in thoracoabdominal computed tomography at high pitch using a third-generation dual-source scanner: image quality and radiation dose performance - Lurz, Markus; Lell, Michael; Wüst, Wolfgang; Eller, Achim; Scharf, Michael; Uder, Michael; May, Matthias (Investigative Radiology, 2015)
The objective of this study was to evaluate the radiation dose and image quality performance of thoracoabdominal examinations with an automated tube voltage selection (tube voltage adaptation), tube current modulation, and high pitch using a third-generation dual-source computed tomography (CT) compared intraindividually with 120-kV examinations with tube current modulation with special attention on clinically relevant lesions in the liver, the lungs, and extrahepatic soft tissues.This study was approved by the institutional review board. Computed tomography of the body was performed using a third-generation dual-source system in 95 patients (mean body mass index, 25 kg/m²; range, 18-35 kg/m²). For 49 of these patients, all calculated tube settings and resulting dose values were recorded for each of the 12 gradual contrast weightings of the tube voltage adaptation algorithm. Spiral CT was performed for all patients with an intermediate weighting (grade 7) in a portal venous phase at 120 reference kV, 180 reference mAs, and pitch of 1.55. Objective image quality was assessed on the basis of contrast-to-noise ratio. Subjective image quality was assessed on the basis of clarity and sharpness of anatomical and pathological structures as well as interfering beam hardening and spiral and motion artifacts (heart, lungs, diaphragm). Previous examinations on a 64-slice scanner served as reference.All examinations were rated good or excellent for clinical diagnosis. Automated tube voltage selection resulted in significantly lower effective radiation dose (9.5 mSv) compared with the reference (12.0 mSv; P < 0.01). Contrast-to-noise ratio and image quality of soft tissue lesions were significantly increased (P < 0.01). Motion artifacts were significantly reduced (P < 0.01).Automated tube voltage adaptation combined with high-pitch protocols allows for a substantial radiation dose reduction while substantially increasing the image quality, even at large-volume exposure.
EVALuna2:14497

Automating implant reconstruction in interstitial brachytherapy of the breast: A hybrid approach combining electromagnetic tracking and image segmentation - Dürrbeck, Christopher; Sauer, Birte; Lotter, Michael; Kreppner, Stephan; Strnad, Vratislav; Fietkau, Rainer; Bert, Christoph (Radiotherapy and Oncology, 2022)
Background and purpose: To develop a method for automatic reconstruction of catheter implants in interstitial brachytherapy (iBT) of the breast by means of electromagnetic tracking (EMT) with the goal of making treatment planning as time-effective and accurate as possible. Materials and methods: The implant geometry of 64 patients was recorded using an afterloader prototype with EMT functionality immediately after the planning CT. EMT data were transferred to the CT image space by rigidly registering the catheter fixation buttons as landmarks. To further improve reconstruction accuracy, the EMT reconstruction points were used as starting points to define small regions of interest (ROI) in the CT image. Within these ROIs, the catheter track was segmented in the CT using image processing operations such as thresholding and blob detection, thus refining the reconstruction. The perpendicular distance between the refined EMT implant reconstruction points and the manually reconstructed catheters by an experienced treatment planner was calculated as a measure of their geometric agreement. Results: Geometrically, the refined EMT based implant reconstruction shows excellent agreement with the manual reconstruction. The median distance across all patients is 0.25 mm and the 95th percentile is 1 mm. Refinement takes approximately 0.5 s per reconstruction point and typically does not exceed 3 min per implant at no user interaction. Conclusion: The refined EMT based implant reconstruction proved to be extremely accurate and fast compared to manual reconstruction. The presented procedure can in principle be easily transferred to clinical routine and therefore has enormous potential to provide significant time savings in iBT treatment planning whilst improving reconstruction accuracy.
CRIS-Team Scopus Importer:2022-10-28
Keywords: Breast cancer; Electromagnetic tracking; Implant reconstruction; Interstitial brachytherapy

Automation of Implant Reconstruction in Interstitial Brachytherapy of the Breast Using Electromagnetic Tracking - Dürrbeck, Christopher; Fietkau, Rainer; Strnad, Vratislav; Bert, Christoph (MEDICAL PHYSICS, 2022)
CRIS-Team WoS Importer:2022-07-08

Automation of radiation treatment planning : Evaluation of head and neck cancer patient plans created by the Pinnacle3scripting and Auto-Planning functions - Speer, Stefan; Klein, Andreas; Kober, Lukas; Weiss, Alexander; Yohannes, Indra; Bert, Christoph (Strahlentherapie und Onkologie, 2017)
BACKGROUND: Intensity-modulated radiotherapy (IMRT) techniques are now standard practice. IMRT or volumetric-modulated arc therapy (VMAT) allow treatment of the tumor while simultaneously sparing organs at risk. Nevertheless, treatment plan quality still depends on the physicist's individual skills, experiences, and personal preferences. It would therefore be advantageous to automate the planning process. This possibility is offered by the Pinnacle3treatment planning system (Philips Healthcare, Hamburg, Germany) via its scripting language or Auto-Planning (AP) module. MATERIALS AND METHODS: AP module results were compared to in-house scripts and manually optimized treatment plans for standard head and neck cancer plans. Multiple treatment parameters were scored to judge plan quality (100 points = optimum plan). Patients were initially planned manually by different physicists and re-planned using scripts or AP. RESULTS AND DISCUSSION: Script-based head and neck plans achieved a mean of 67.0 points and were, on average, superior to manually created (59.1 points) and AP plans (62.3 points). Moreover, they are characterized by reproducibility and lower standard deviation of treatment parameters. Even less experienced staff are able to create at least a good starting point for further optimization in a short time. However, for particular plans, experienced planners perform even better than scripts or AP. Experienced-user input is needed when setting up scripts or AP templates for the first time. Moreover, some minor drawbacks exist, such as the increase of monitor units (+35.5% for scripted plans). CONCLUSION: On average, automatically created plans are superior to manually created treatment plans. For particular plans, experienced physicists were able to perform better than scripts or AP; thus, the benefit is greatest when time is short or staff inexperienced.
EVALuna2:33035

Automatisation of catheter reconstruction in interstitial breast BT using electromagnetic tracking - Dürrbeck, Christopher; Abu-Hossin, N.; Lotter, M.; Kreppner, Stephan; Lubgan, Dorota; Fietkau, Rainer; Strnad, Vratislav; Bert, Christoph (RADIOTHERAPY AND ONCOLOGY, 2022)
CRIS-Team WoS Importer:2022-07-15

A web based cross-platform application for teleconsultation in radiology - Kammerer, Ferdinand J.; Hammon, Matthias; Schlechtweg, Philipp; Uder, Michael; Schwab, Siegfried (Journal of Telemedicine and Telecare, 2015)
The growing complexity of radiologic examinations and interventional procedures requires frequent exchange of knowledge. Consequently a simple way to share and discuss patient images between radiology experts and with colleagues from other medical disciplines is needed. Aims of this work were the development and initial performance evaluation of a fast and user friendly, platform independent teleconsultation system for medical imaging. A local back end system receives DICOM images and generates anonymized JPEG files that are uploaded to an internet webserver. The front end running on that webserver comprises an image viewer with a specially developed pointer element for indicating findings to collaborative partners. The front end that uses only standard web technologies works on a variety of different platforms, mobile devices and desktop computers. Images can be accessed by simply calling up a special internet address in a web browser that may be exchanged between users (e.g. via email). A speed evaluation of the system showed good results: For example the preparation and upload of a standard head CT took less than 21 seconds. The data volume of the same series and the viewer application could be transferred to a mobile phone in less than 42 seconds via a UMTS network or in less than 3 seconds via a HSPA network. The presented system with its minimal hard- and software requirements, its simplicity and platform independence might be a promising tool in the increasingly important area of teleconsultation.
EVALuna2:14496

Baseline Quality of Life of Physical Function Is Highly Relevant for Overall Survival in Advanced Rectal Cancer - Fitz, Tim; Sörgel, Christopher; Rutzner, Sandra; Hecht, Markus; Fietkau, Rainer; Distel, Luitpold (Healthcare, 2022)
In advanced rectal cancer, neoadjuvant radiochemotherapy and total mesorectal excision lead to long overall survival. The quality of life (QOL) of the patients is clearly related to the prognosis. Our question was whether the prognosis can be represented with only one question or one score from the QOL questionnaires. 360 consecutively recruited patients diagnosed with advanced rectal cancer were questioned during radiochemotherapy and a follow-up of 8 years. The questionnaires QLQ-C30 and QLQ-CR38 were used; 10 functional and 17 symptom scores were calculated. The functional score “physical function” and the symptom scores “fatigue”, “nausea and vomiting”, “pain” and “appetite loss” were highly prognostic (p < 0.001) for overall survival. “Physical function” was highly prognostic at all time points up to 1 year after starting therapy (p ≤ 0.001). The baseline “physical function” score divided the cohort into a favorable group with an 8-year overall survival rate of 70.4% versus an unfavorable group with 47.5%. In the multivariable analysis, baseline “physical function”, age and distant metastases were independent predictors of overall survival. The score “physical function” is a powerful unrelated risk factor for overall survival in patients with rectal cancer. Future analyses should study whether increased “physical function” after diagnosis could improve survival.
CRIS-Team Scopus Importer:2022-01-28
Keywords: Age; Physical function; Quality of life; Radiochemotherapy; Rectal cancer

Basics of Radiation Biology When Treating Hyperproliferative Benign Diseases - Roedel, Franz; Fournier, Claudia; Wiedemann, Julia; Merz, Felicitas; Gaipl, Udo; Frey, Benjamin; Keilholz, Ludwig; Seegenschmiedt, M. Heinrich; Roedel, Claus; Hehlgans, Stephanie (Frontiers in Immunology, 2017)
For decades, low- and moderate-dose radiation therapy (RT) has been shown to exert a beneficial therapeutic effect in a multitude of non-malignant conditions including painful degenerative muscoloskeletal and hyperproliferative disorders. Dupuytren and Ledderhose diseases are benign fibroproliferative diseases of the hand/foot with fibrotic nodules and fascial cords, which determine debilitating contractures and deformities of fingers/toes, while keloids are exuberant scar formations following burn damage, surgery, and trauma. Although RT has become an established and effective option in the management of these diseases, experimental studies to illustrate cellular composites and factors involved remain to be elucidated. More recent findings, however, indicate the involvement of radiation-sensitive targets like mitotic fibroblasts/myofibroblasts as well as inflammatory cells. Radiation-related molecular mechanisms affecting these target cells include the production of free radicals to hamper proliferative activity and interference with growth factors and cytokines. Moreover, an impairment of activated immune cells involved in both myofibroblast proliferative and inflammatory processes may further contribute to the clinical effects. We here aim at briefly describing mechanisms contributing to a modulation of proliferative and inflammatory processes and to summarize current concepts of treating hyperproliferative diseases by low and moderate doses of ionizing radiation.
EVALuna2:32930

Bayesian Cure Rate Modeling of Local Tumor Control: Evaluation in Stereotactic Body Radiation Therapy for Pulmonary Metastases - Klement, Rainer J.; Allgaeuer, Michael; Andratschke, Nicolaus; Blanck, Oliver; Boda-Heggemann, Judit; Dieckmann, Karin; Duma, Marciana; Ernst, Iris; Flentje, Michael; Ganswindt, Ute; Hass, Peter; Henkenberens, Christoph; et al. (International Journal of Radiation Oncology Biology Physics, 2016)
Most radiobiological models for prediction of tumor control probability (TCP) do not account for the fact that many events could remain unobserved because of censoring. We therefore evaluated a set of TCP models that take into account this censoring.We applied 2 fundamental Bayesian cure rate models to a sample of 770 pulmonary metastasis treated with stereotactic body radiation therapy at German, Austrian, and Swiss institutions: (1) the model developed by Chen, Ibrahim and Sinha (the CIS99 model); and (2) a mixture model similar to the classic model of Berkson and Gage (the BG model). In the CIS99 model the number of clonogens surviving the radiation treatment follows a Poisson distribution, whereas in the BG model only 1 dominant recurrence-competent tissue mass may remain. The dose delivered to the isocenter, tumor size and location, sex, age, and pretreatment chemotherapy were used as covariates for regression.Mean follow-up time was 15.5 months (range: 0.1-125). Tumor recurrence occurred in 11.6% of the metastases. Delivered dose, female sex, peripheral tumor location and having received no chemotherapy before RT were associated with higher TCP in all models. Parameter estimates of the CIS99 were consistent with the classical Cox proportional hazards model. The dose required to achieve 90% tumor control after 15.5 months was 146 (range: 114-188) Gy10 in the CIS99 and 133 (range: 101-164) Gy10 in the BG model; however, the BG model predicted lower tumor control at long (?20 months) follow-up times and gave a suboptimal fit to the data compared to the CIS99 model.Biologically motivated cure rate models allow adding the time component into TCP modeling without being restricted to the follow-up period which is the case for the Cox model. In practice, application of such models to the clinical setting could allow for adaption of treatment doses depending on whether local control should be achieved in the short or longer term.
EVALuna2:18357

Behavioural effects of APH199, a selective dopamine D4 receptor agonist, in animal models - Chestnykh, Daria; Graßl, Fabian; Pfeifer, Conrad; Dülk, Jonas; Ebner, Chiara; Walters, Mona; von Hörsten, Stephan; Kornhuber, Johannes; Kalinichenko, Liubov; Heinrich, Markus; Müller, Christian P. (Psychopharmacology, 2023)
Rationale: The dopamine D4 receptors (DRD4) play a key role in numerous brain functions and are involved in the pathogenesis of various psychiatric disorders. DRD4 ligands have been shown to moderate anxiety, reward and depression-like behaviours, and cognitive impairments. Despite a series of promising but ambiguous findings, the therapeutic advantages of DRD4 stimulation remain elusive. Objectives: The investigation focused on the behavioural effects of the recently developed DRD4 agonist, APH199, to evaluate its impact on anxiety, anhedonia, behavioural despair, establishment and retrieval of alcohol reinforcement, and amphetamine (AMPH)-induced symptoms. Methods: Male C57BL/6 J mice and Sprague–Dawley rats were examined in five independent experiments. We assessed APH199 (0.1–5 mg/kg, i.p.) effects on a broad range of behavioural parameters in the open field (OF) test, conditioned place preference test (CPP), elevated plus maze (EPM), light–dark box (LDB), novelty suppressed feeding (NSF), forced swim test (FST), sucrose preference test (SPT), AMPH-induced hyperlocomotion test (AIH), and prepulse inhibition (PPI) of the acoustic startle response in AMPH-sensitized rats. Results: APH199 caused mild and sporadic anxiolytic and antidepressant effects in EPM and FST, but no remarkable impact on behaviour in other tests in mice. However, we found a significant increase in AMPH-induced hyperactivity, suggesting an exaggeration of the psychotic-like responses in the AMPH-sensitized rats. Conclusions: Our data challenged the hypothesis of the therapeutic benefits of DRD4 agonists, pointing out a possible aggravation of psychosis. We suggest a need for further preclinical studies to ensure the safety of antipsychotics with DRD4 stimulating properties.
CRIS-Team Scopus Importer:2023-03-10
Keywords: Alcohol; Anxiety; APH199; Depression; DRD4 agonist; Psychosis; Schizophrenia

Beim HPV-assoziierten Oropharynxkarzinom ist die Radiochemotherapie mit Cisplatin der Bioradiotherapie mit Cetuximab in Bezug auf das Gesamtüberleben überlegen - Semrau, Sabine (Strahlentherapie und Onkologie, 2019)
CRIS-Team Scopus Importer:2019-05-09

Benchmarking ChatGPT-4 on a radiation oncology in-training exam and Red Journal Gray Zone cases: potentials and challenges for AI-assisted medical education and decision making in radiation oncology - Huang, Yixing; Gomaa, Ahmed; Semrau, Sabine; Haderlein, Marlen; Lettmaier, Sebastian; Weissmann, Thomas; Grigo, Johanna; Ben Tkhayat, Hassen; Frey, Benjamin; Gaipl, Udo; Distel, Luitpold; Maier, Andreas; et al. (Frontiers in Oncology, 2023)
Keywords: Large language model; Radiotherapy; Natural language processing; Artificial intelligence; Gray Zone; Clinical decision support (CDS)

Bevacizumab Plus Irinotecan Versus Temozolomide in Newly Diagnosed O6-Methylguanine-DNA Methyltransferase Nonmethylated Glioblastoma: The Randomized GLARIUS Trial - Herrlinger, Ulrich; Schaefer, Niklas; Steinbach, Joachim P.; Weyerbrock, Astrid; Hau, Peter; Goldbrunner, Roland; Friedrich, Franziska; Rohde, Veit; Ringel, Florian; Schlegel, Uwe; Sabel, Michael; Ronellenfitsch, Michael W.; et al. (Journal of Clinical Oncology, 2016)
In patients with newly diagnosed glioblastoma that harbors a nonmethylated O(6)-methylguanine-DNA methyltransferase promotor, standard temozolomide (TMZ) has, at best, limited efficacy. The GLARIUS trial thus explored bevacizumab plus irinotecan (BEV+IRI) as an alternative to TMZ.In this phase II, unblinded trial 182 patients in 22 centers were randomly assigned 2:1 to BEV (10 mg/kg every 2 weeks) during radiotherapy (RT) followed by maintenance BEV (10 mg/kg every 2 weeks) plus IRI(125 mg/m(2) every 2 weeks) or to daily TMZ (75 mg/m(2)) during RT followed by six courses of TMZ (150-200 mg/m(2)/d for 5 days every 4 weeks). The primary end point was the progression-free survival rate after 6 months (PFS-6).In the modified intention-to-treat (ITT) population, PFS-6 was increased from 42.6% with TMZ (95% CI, 29.4% to 55.8%) to 79.3% with BEV+IRI (95% CI, 71.9% to 86.7%; P <.001). PFS was prolonged from a median of 5.99 months (95% CI, 2.7 to 7.3 months) to 9.7 months (95% CI, 8.7 to 10.8 months; P < .001). At progression, crossover BEV therapy was given to 81.8% of all patients who received any sort of second-line therapy in the TMZ arm. Overall survival (OS) was not different in the two arms: the median OS was 16.6 months (95% CI, 15.4 to 18.4 months) with BEV+IRI and was 17.5 months (95% CI, 15.1 to 20.5 months) with TMZ. The time course of quality of life (QOL) in six selected domains of the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire (QLQ) -C30 and QLQ-BN20 (which included cognitive functioning), of the Karnofsky performance score, and of the Mini Mental State Examination score was not different between the treatment arms.BEV+IRI resulted in a superior PFS-6 rate and median PFS compared with TMZ. However, BEV+IRI did not improve OS, potentially because of the high crossover rate. BEV+IRI did not alter QOL compared with TMZ.
EVALuna2:18349

Bifunctional Au-Fe3O4 Nanoheterodimers Acting as X-ray Protector in Healthy Cells and as X-ray Enhancer in Tumor Cells - Klein, Stefanie; Smuda, Matthias; Harreiß, Christina; Menter, Christina; Distel, Luitpold; Kryschi, Carola (ACS Applied Materials and Interfaces, 2019)
Bifunctional Au-Fe3O4 nanoheterodimers were synthesized by thermally decomposing Fe(III)oleate on gold nanoparticles followed by functionalizing with tiron, 2,3-dihydroxybenzoic acid, or caffeic acid. These catechol derivatives are antioxidative and thus are predicted to function as superoxide scavengers. In particular, caffeic acid lost its antioxidant capacity, although it was covalently linked through its carboxyl moiety to the Fe3O4 surface. Tiron was shown to bind via its catechol group to the Au-Fe3O4 nanoheterodimers, and 2,3-dihydroxybenzoic was just physisorbed between the oleic acid surface structures. Caffeic-acid stabilized Au-Fe3O4 nanoheterodimers turned out to act as X-ray protector in healthy cells but as X-ray enhancing agents in cancer cells. Furthermore, these functionalized Au-Fe3O4 nanoheterodimers were found to inhibit the migratory capacity of the cancer cells.
CRIS-Team Scopus Importer:2019-11-05
Keywords: 2; 3-dihydroxybenzoic acid; Au-Fe; caffeic acid; cell migration; radioprotector; radiosensitizer; tiron

Bioabsorbable Unsintered Hydroxyapatite/Poly-l-Lactic Acid Pin Fixation of Osteochondritis Dissecans in Adolescents: Initial Experiences - Zeilinger, Martin Georg; Autenrieth, Christian; Remmel, Kerstin; Schuh, Alexander; Hammon, Matthias; Schraml, Annemarie; Uder, Michael; Rompel, Oliver (Zeitschrift für Orthopädie und Unfallchirurgie, 2020)
Background This study sought to retrospectively evaluate the clinical and magnetic resonance imaging (MRI) outcomes of u-HA/PLLA pin (u-HA/PLLA: hydroxyapatite/poly-L-lactic acid) pin fixation of unstable osteochondritis dissecans (OCD) lesions of the knee. Methods Seven adolescent patients (four females and three males) with arthroscopically unstable OCD lesions of the knee were included. The mean age at diagnosis was 13.1 years. Clinical results were evaluated preoperatively and during follow-up using the Ogilvie-Harris score (0-15 points). MRI scans were performed preoperatively and during follow-up, with results evaluated using the Dipaola classification (grades 1-4). Mean follow-up time was 29 months. Results The median Ogilvie-Harris score improved from 13 points (range: 10-14 points) to 15 points (range: 13-15 points). Separately, the median Dipaola score improved from 3 points (range: 2-4 points) to 1 point (range: 1-4 points). No complications such as infection, synovitis, or intra-articular adhesion were observed. Conclusions Initial experiences using bioabsorbable u-HA/PLLA pins for the refixation of unstable OCD lesions in adolescents in the knee are promising, and MRI provides excellent monitoring of healing.
CRIS-Team Scopus Importer:2020-12-25
Keywords: bioabsorbable pins; juvenile; Osteochondritis dissecans; u-HA/PLLA

Biocompatibility of Dextran-Coated 30 nm and 80 nm Sized SPIONs towards Monocytes, Dendritic Cells and Lymphocytes - Zschiesche, Lisa; Janko, Christina; Friedrich, Bernhard; Frey, Benjamin; Band, Julia; Lyer, Stefan; Alexiou, Christoph; Unterweger, Harald (Nanomaterials, 2023)
Dextran-coated superparamagnetic iron oxide nanoparticles (SPIONDex) of various sizes can be used as contrast agents in magnetic resonance imaging (MRI) of different tissues, e.g., liver or atherosclerotic plaques, after intravenous injection. In previous studies, the blood compatibility and the absence of immunogenicity of SPIONDex was demonstrated. The investigation of the interference of SPIONDex with stimulated immune cell activation is the aim of this study. For this purpose, sterile and endotoxin-free SPIONDex with different hydrodynamic sizes (30 and 80 nm) were investigated for their effect on monocytes, dendritic cells (DC) and lymphocytes in concentrations up to 200 µg/mL, which would be administered for use as an imaging agent. The cells were analyzed using flow cytometry and brightfield microscopy. We found that SPIONDex were hardly taken up by THP-1 monocytes and did not reduce cell viability. In the presence of SPIONDex, the phagocytosis of zymosan and E. coli by THP-1 was dose-dependently reduced. SPIONDex neither induced the maturation of DCs nor interfered with their stimulated maturation. The particles did not induce lymphocyte proliferation or interfere with lymphocyte proliferation after stimulation. Since SPIONDex rapidly distribute via the blood circulation in vivo, high concentrations were only reached locally at the injection site immediately after application and only for a very limited time. Thus, SPIONDex can be considered immune compatible in doses required for use as an MRI contrast agent.
CRIS-Team Scopus Importer:2023-01-20
Keywords: biocompatibility; immune response; magnetic resonance imaging (MRI); nanomedicine; superparamagnetic iron oxide nanoparticles (SPION)

BIOPHYSICS-08 Response of bone marrow progenitor cells to ionizing irradiation - Cucu, Aljona; Kraft, Daniela; Hirschmann, M; Deloch, Lisa; Frey, Benjamin; Gaipl, Udo; Durante, Marco; Fournier, Claudia (2014)

BIOPHYSICS-22 Time course of radiation induced chromosome aberrations in mouse bone marrow cells - Paz, Nerea; Nasonova, Elena; Deloch, Lisa; Frey, Benjamin; Gaipl, Udo; Durante, Marco; Ritter, Sylvia (2014)

Blockade of IL-36 Receptor Signaling Does Not Prevent from TNF-Induced Arthritis - Derer, Anja; Groetsch, Bettina; Harre, Ulrike; Böhm, Christina; Towne, Jennifer; Schett, Georg; Frey, Silke; Hueber, Axel (PLoS ONE, 2014)
Interleukin (IL)-36? is a newly described member of the IL-1 cytokine family with a known inflammatory and pathogenic function in psoriasis. Recently, we could demonstrate that the receptor (IL-36R), its ligand IL-36? and its antagonist IL-36Ra are expressed in synovial tissue of arthritis patients. Furthermore, IL-36? induces MAP-kinase and NF?B signaling in human synovial fibroblasts with subsequent expression and secretion of pro-inflammatory cytokines.To understand the pathomechanism of IL-36 dependent inflammation, we investigated the biological impact of IL-36? signaling in the hTNFtg mouse. Also the impact on osteoclastogenesis by IL-36? was tested in murine and human osteoclast assays.Diseased mice showed an increased expression of IL-36R and IL-36? in inflamed knee joints compared to wildtype controls. However, preventively treating mice with an IL-36R blocking antibody led to no changes in clinical onset and pattern of disease. Furthermore, blockade of IL-36 signaling did not change histological signs of TNF-induced arthritis. Additionally, no alteration on bone homeostasis was observed in ex vivo murine and human osteoclast differentiation assays.Thus we conclude that IL-36? does not affect the development of inflammatory arthriti
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Blood pressure reduction after renal denervation in patients with or without chronic kidney disease - Günes-Altan, Merve; Schmid, Axel; Ott, Christian; Bosch, Agnes; Pietschner, Robert; Schiffer, Mario; Uder, Michael; Schmieder, Roland; Kannenkeril, Dennis (Clinical Kidney Journal, 2024)
Background. Renal denervation (RDN) has emerged as an adjacent option for the treatment of hypertension. This analysis of the Erlanger registry aimed to compare the blood pressure (BP)-lowering effects and safety of RDN in patients with and without chronic kidney disease (CKD). Methods. In this single-center retrospective analysis, 47 patients with and 127 without CKD underwent radiofrequency-, ultrasound- or alcohol-infusion-based RDN. Office and 24-h ambulatory BP and estimated glomerular filtration rate (eGFR) were measured at baseline, and after 6 and 12 months. Results. A total of 174 patients with a mean age of 59.0 ± 10 years were followed up for 12 months. At baseline, mean eGFR was 55.8 ± 21 mL/min/1.73 m2 in patients with CKD and 87.3 ± 13 mL/min/1.73 m2 in patients without CKD. There was no significant eGFR decline in either of the groups during 12 months of follow-up. In patients without CKD, office systolic and diastolic BP were reduced by –15.3 ± 17.5/–7.9 ± 10.8 mmHg 6 months after RDN and by –16.1 ± 18.2/–7.7 ± 9.6 mmHg 12 months after RDN. In patients with CKD, office systolic and diastolic BP were reduced by –10.7 ± 24.0/–5.8 ± 13.2 mmHg 6 months after RDN and by –15.1 ± 24.9/–5.9 ± 12.9 mmHg 12 months after RDN. Accordingly, in patients without CKD, 24-h ambulatory systolic and diastolic BP were reduced by –7.2 ± 15.8/–4.9 ± 8.8 mmHg 6 months after RDN and by –9.0 ± 17.0/–6.2 ± 9.8 mmHg 12 months after RDN. In patients with CKD, 24-h systolic and diastolic BP were reduced by –7.4 ± 12.9/–4.2 ± 9.9 mmHg 6 months after RDN and by –8.0 ± 14.0/–3.6 ± 9.6 mmHg 12 months after RDN. There was no difference in the reduction of office and 24-h ambulatory BP between the two groups at any time point (all P > .2). Similar results have been found for the 6 months data. With exception of rare local adverse events, we did not observe any safety signals. Conclusion. According to our single-center experience, we observed a similar reduction in 24-h, day and night-time ambulatory BP as well as in-office BP in patients with and without CKD at any time point up to 12 months. We conclude that RDN is an effective and safe treatment option for patients with hypertension and CKD.
CRIS-Team Scopus Importer:2024-01-26
Keywords: blood pressure; chronic kidney disease; hypertension; post-hoc analysis; renal denervation

Both Gender and Inflammatory Status play a Role in the low-dose Rontgen Therapy Effect on Synovial Fibroblasts - Völlings, Antonia; Piltz, Margaux; Titova, E.; Wolff, Teresa; Weissmann, Thomas; Fietkau, Rainer; Frey, Benjamin; Gaipla, U.; Deloch, Lisa (STRAHLENTHERAPIE UND ONKOLOGIE, 2022)
CRIS-Team WoS Importer:2022-06-03

Brachytherapy boost in anal canal cancer – A GEC ESTRO PDR task force meta-analysis - Annede, Pierre; Ferre, Marjorie; Kirisits, Christian; Pieters, Bradley R.; Schmid, Maximilian; Strnad, Vratislav; Westerveld, Henrike; Chargari, Cyrus (Clinical and Translational Radiation Oncology, 2023)
Purpose: A meta-analysis is presented comparing clinical outcomes and toxicities between high dose rate (HDR) and pulsed dose rate (PDR) brachytherapy (BT) for anal cancer. Methods and material: Retrospective or prospective clinical trials were identified on electronical databases. Data were collected per Preferred Reporting Items for Systematic Reviews and meta-Analyses guidelines. Pooled effect size for HDR and PDR BT were compared using subgroup analyses. Results: Nine retrospective studies with a total of 481 patients treated were included of which 219 with HDR and 262 with PDR. Significant differences were observed between the two groups for baseline characteristics and treatment. The cumulative proportion of stage T3-T4 was lower in the HDR group, 0.15 [95 % confidence interval (CI) 0.07–0.29] vs 0.27 [95 %CI 0.09–0.57] in the LDR group, p < 0.001. Lower BT doses (in equivalent 2-Gy fraction dose) were given for patients in the HDR group, 11.9 Gy [95 %CI 8.2–15.5] vs 19.5 Gy [95 %CI 15.0–24.0] in the PDR group, p < 0.001. No significant differences were found for clinical outcomes or toxicities. The pooled effect size of the overall survival at 5 years for HDR and PDR was respectively 0.82 [95 %CI 0.70–0.94] and 0.82 [95 %CI 0.73–0.91], p > 0.99. The 5 years local control was 0.86 [95 % confidence interval (CI) 0.81–0.91] and 0.83 [95 %CI 0.77–0.89], p = 0.62. Cumulative toxicity-related colostomy proportion was 0.04 [95 %CI 0.02–0.09] and 0.03 [95 %CI 0.02–0.07], p = 0.85. Conclusion: Both modalities provided a good profile of tolerance and are effective organ conservative strategies for patients with anal canal cancer. In parallel with ongoing developments to better determine the optimal fractionation and dose for HDR-BT treatments, especially in large tumors, PDR BT still has a crucial role for dose escalation strategy in advanced cases.
CRIS-Team Scopus Importer:2023-02-24
Keywords: Anal cancer; Brachytherapy; High-dose rate brachytherapy; Local control; Morbidity; Pulsed-dose rate brachytherapy; Toxicity

Brachytherapy focal dose escalation using ultrasound based tissue characterization by patients with non-metastatic prostate cancer: Five-year results from single-center phase 2 trial - Strnad, Vratislav; Lotter, Michael; Kreppner, Stephan; Fietkau, Rainer (Brachytherapy, 2022)
PURPOSE: This prospective trial investigates side effects and efficacy of focal dose escalation with brachytherapy for patients with prostate cancer. METHODS AND MATERIALS: In the Phase II, monocentric prospective trial 101 patients with low-/intermediate- and high-risk prostate cancer were enrolled between 2011 and 2013. Patients received either PDR-/HDR-brachytherapy alone with 86–90 Gy (EQD2, α/β = 3 Gy) or PDR-/HDR-brachytherapy as boost after external beam radiation therapy up to a total dose of 91–96 Gy (EQD2, α/β = 3 Gy). Taking place brachytherapy all patients received the simultaneous integrated focal boost to the intra-prostatic tumor lesions visible in computer-aided ultrasonography (HistoScanning™) - up to a total dose of 108–119 Gy (EQD2, α/β = 3 Gy). The primary endpoint was toxicity. Secondary endpoints were cumulative freedom from local recurrence, PSA-free survival, distant metastases-free survival, and overall survival. This trial is registered with ClinicalTrials.gov, number NCT01409876. Results: Median follow-up was 65 months. Late toxicity was generally low with only four patients scoring urinary grade 3 toxicity (4/101, 4%). Occurrence of any grade of late rectal toxicities was very low. We did not register any grade ≥2 of late rectal toxicities. The cumulative 5 years local recurrence rate (LRR) for all patients was 1%. Five years- biochemical disease-free survival estimates according Kaplan-Meier were 98,1% and 81,3% for low-/intermediate-risk and high-risk patients, respectively. Five years metastases-free survival estimates according Kaplan-Meier were 98,0% and 83,3% for all patients, low-/intermediate-risk and high-risk patients, respectively. Conclusions: The 5 years-results from this Phase II Trial show that focal dose escalation with computer-aided ultrasonography and brachytherapy for patients with non-metastatic prostate cancer is safe and effective.
CRIS-Team Scopus Importer:2022-04-15
Keywords: Brachytherapy; Focal dose escalation; Prostate cancer

Brachytherapy training survey among radiation oncology residents in Europe - Sturdza, Alina Emiliana; Stephanides, Marianne; Jurgenliemk-Schulz, Ina; Eriksen, Jesper Grau; Benstead, Kim; Hoskin, Peter; Vlad, Stefanel; Escande, Alexandre; Corradini, Stefanie; Knoth, Johannes; Westerveld, Henrike; Tagliaferri, Luca; et al. (Radiotherapy and Oncology, 2022)
We aim to investigate the current state of brachytherapy (BT) training among the radiation oncology trainees in Europe. Material and methods: A 22-question online survey based on the one by the American Association of Radiation Oncology Residents (2017) with added queries pertinent to training in Europe was sent to 1450 residents in two iterations. These included site-specific training, volume of experience, barriers to training, institutional support, and preferences for further education. Responses to individual statements were given on a 1 to 5 Likert-type scale. The answers were reported by junior (≤3 years of training) and senior years of training (year of training 4/5/6 and junior staff). Descriptive statistics were used to describe frequencies. Results: Residents from 21 European countries participated, 445 (31%) responded. 205 (47%) were senior residents. 60% residents consider that performing BT independently at the end of residency is very or somewhat important. Confidence in joining a brachytherapy practice at the end of residency was high or somewhat high in 34% of senior residents. They reported as barriers to achieving independence in BT to be lack of appropriate didactic/procedural training from supervisors (47%) and decreased case load (31%). 68% reported their program lacks a formal BT curriculum and standardized training assessment. Conclusions: Residents in Europe, feel independent BT practice is very or somewhat important, but do not feel confident they will achieve this goal. To address this gap, efforts are needed to develop and implement a formal and comprehensive BT curriculum with easy access to trained instructors.
CRIS-Team Scopus Importer:2022-11-25
Keywords: Brachytherapy training; Education; Radiation oncology residents

Brain volume after whole-brain radiotherapy: prognostic relevance and protective factors - Putz, Florian; Hoffmann, Christian; Distel, Luitpold; Gryc, Thomas; Knippen, S.; Fietkau, Rainer (2017)
EVALuna2:32901

Brain volume reduction after whole-brain radiotherapy: quantification and prognostic relevance - Hoffmann, Christian; Distel, Luitpold; Knippen, Stefan; Gryc, Thomas; Schmidt, Manuel; Fietkau, Rainer; Putz, Florian (Neuro-Oncology, 2018)
Background: Recent studies have questioned the value of adding whole-brain radiotherapy (WBRT) to stereotactic radiosurgery (SRS) for brain metastasis treatment. Neurotoxicity, including radiation-induced brain volume reduction, could be one reason why not all patients benefit from the addition of WBRT. In this study, we quantified brain volume reduction after WBRT and assessed its prognostic significance. Methods: Brain volumes of 91 patients with cerebral metastases were measured during a 150-day period after commencing WBRT and were compared with their pretreatment volumes. The average daily relative change in brain volume of each patient, referred to as the "brain volume reduction rate," was calculated. Univariate and multivariate Cox regression analyses were performed to assess the prognostic significance of the brain volume reduction rate, as well as of 3 treatment-related and 9 pretreatment factors. A one-way analysis of variance was used to compare the brain volume reduction rate across recursive partitioning analysis (RPA) classes. Results: On multivariate Cox regression analysis, the brain volume reduction rate was a significant predictor of overall survival after WBRT (P < 0.001), as well as the number of brain metastases (P = 0.002) and age (P = 0.008). Patients with a relatively favorable prognosis (RPA classes 1 and 2) experienced significantly less brain volume decrease after WBRT than patients with a poor prognosis (RPA class 3) (P = 0.001). There was no significant correlation between delivered radiation dose and brain volume reduction rate (P = 0.147). Conclusion: In this retrospective study, a smaller decrease in brain volume after WBRT was an independent predictor of longer overall survival.
EVALuna2:36468

Breast brachytherapy - Strnad, Vratislav; Yashar, Catheryn (Brachytherapy, 2020)
Accelerated partial breast irradiation with brachytherapy is a treatment method with a very low risk profile. In fact, accelerated partial breast irradiation brachytherapy has been proven in randomized trials to have fewer late side effects than whole-breast irradiation. Notably, Grade 3 late side effects are extremely rare, and excellent to good cosmetic results are observed in well over 90% of patients. In this article, published side effects of breast brachytherapy are reviewed and appropriate management discussed.
CRIS-Team Scopus Importer:2021-04-19
Keywords: Brachytherapy; Breast; Side effects

Broadband microwave spiral applicator (105–125 MHz) for in vitro examinations of hyperthermia-induced tumor cell death forms–first analyses with human breast cancer cells - Walter, Jannik; Hader, Michael; Sengedorj, Azzaya; Fietkau, Rainer; Frey, Benjamin; Gaipl, Udo (International Journal of Hyperthermia, 2023)
Purpose: Local tumor heating with microwave applicators has been used in multimodal breast cancer therapies. This hyperthermia allows to target small regions while marginally affecting healthy tissue. However, most preclinical examinations only use simplified heating methods. Microwave applicators employed for deep heating to provide the greatest depth of penetration operate in the tens to hundreds frequency. Therefore, we aimed to adapt and test a clinically often used broadband spiral applicator (105–125 MHz) for hyperthermia with clinically wanted temperatures of 41 and 44 °C in in vitro settings with human breast cancer cell lines and with simulations. Material and Methods: A clinically used spiral-microwave applicator (105–125 MHz) was the basis for the construction, simulation, and optimization of the in vitro HT set-up under stationary conditions. Microwave effects on tumor cell death of two human breast cancer cell lines (hormone-receptor positive MCF-7 and triple-negative MDA-MB-231) were compared with conventional heating in a contact-heating chamber. Cell death forms were analyzed by AnnexinV/Propidium iodide staining. Results: An in vitro spiral applicator microwave-based heating system that is effective at applying heat directly to adherent breast cancer cells in cell culture flasks with medium was developed. Simulations with COMSOL proved appropriate heat delivery and an optimal energy coupling at a frequency of 111 ± 2.5 MHz. Apoptosis and necrosis induction and significantly higher cell death rates than conventional heating at both temperatures were observed, and MCF-7 showed higher death rates than MDA-MB-231 tumor cells. Conclusions: Well-characterized in vitro heating systems are mandatory for a better understanding of the biological effects of hyperthermia in tumor therapies and to finally determine optimized clinical treatment schemes.
CRIS-Team Scopus Importer:2023-10-20
Keywords: 105–125 MHz spiral applicator; breast cancer; cell death forms; microwave frequency; Microwave hyperthermia; multimodal tumor treatment

Caffeic Acid, Quercetin and 5-Fluorocytidine-Functionalized Au-Fe3O4 Nanoheterodimers for X-ray-Triggered Drug Delivery in Breast Tumor Spheroids - Klein, Stefanie; Distel, Luitpold; Neuhuber, Winfried; Kryschi, Carola (Nanomaterials, 2021)
Au-Fe3O4 nanoheterodimers (NHD) were functionalized with the natural and synthetic anticancer drugs caffeic acid (CA), quercetin (Q) and 5-fluorocytidine (5FC). Their X-radiation dose-enhancing potential and chemotherapeutic efficacy for bimodal cancer therapy were investigated by designing multicellular tumor spheroids (MCTS) to in vitro avascular tumor models. MCTS were grown from the breast cancer cell lines MCF-7, MDA-MB-231, and MCF-10A. The MCF-7, MDA-MB-231 and MCF-10A MCTS were incubated with NHD-CA, NHD-Q, or NHD-5FC and then exposed to fractionated X-radiation comprising either a single 10 Gy dose, 2 daily single 5 Gy doses or 5 daily single 2 Gy doses. The NHD-CA, NHD-Q, and NHD-5FC affected the growth of X-ray irradiated and non-irradiated MCTS in a different manner. The impact of the NHDs on the glycolytic metabolism due to oxygen deprivation inside MCTS was assessed by measuring lactate secretion and glucose uptake by the MCTS. The NHD-CA and NHD-Q were found to act as X-radiation dose agents in MCF-7 MCTS and MDA-MB-231 MCTS and served as radioprotector in MCF-10A MCTS. X-ray triggered release of CA and Q inhibited lactate secretion and thereupon disturbed glycolytic reprogramming, whereas 5FC exerted their cytotoxic effects on both, healthy and tumor cells, after their release into the cytosol.
CRIS-Team WoS Importer:2021-06-11

Calibration by differentiation – Self-supervised calibration for X-ray microscopy using a differentiable cone-beam reconstruction operator - Thies, Mareike; Wagner, Fabian; Huang, Yixing; Gu, Mingxuan; Kling, Lasse; Pechmann, Sabrina; Aust, Oliver; Grüneboom, Anika; Schett, Georg; Christiansen, Silke H.; Maier, Andreas (Journal of Microscopy, 2022)
High-resolution X-ray microscopy (XRM) is gaining interest for biological investigations of extremely small-scale structures. XRM imaging of bones in living mice could provide new insights into the emergence and treatment of osteoporosis by observing osteocyte lacunae, which are holes in the bone of few micrometers in size. Imaging living animals at that resolution, however, is extremely challenging and requires very sophisticated data processing converting the raw XRM detector output into reconstructed images. This paper presents an open-source, differentiable reconstruction pipeline for XRM data which analytically computes the final image from the raw measurements. In contrast to most proprietary reconstruction software, it offers the user full control over each processing step and, additionally, makes the entire pipeline deep learning compatible by ensuring differentiability. This allows fitting trainable modules both before and after the actual reconstruction step in a purely data-driven way using the gradient-based optimizers of common deep learning frameworks. The value of such differentiability is demonstrated by calibrating the parameters of a simple cupping correction module operating on the raw projection images using only a self-supervisory quality metric based on the reconstructed volume and no further calibration measurements. The retrospective calibration directly improves image quality as it avoids cupping artifacts and decreases the difference in gray values between outer and inner bone by 68% to 94%. Furthermore, it makes the reconstruction process entirely independent of the XRM manufacturer and paves the way to explore modern deep learning reconstruction methods for arbitrary XRM and, potentially, other flat-panel CT systems. This exemplifies how differentiable reconstruction can be leveraged in the context of XRM and, hence, is an important step toward the goal of reducing the resolution limit of in-vivo bone imaging to the single micrometer domain.
Keywords: X-ray microscopy; computed tomography; inverse problems; reconstruction; deep learning; known operator learning

Cancer Cell Death-Inducing Radiotherapy: Impact on Local Tumour Control, Tumour Cell Proliferation and Induction of Systemic Anti-tumour Immunity - Frey, Benjamin; Derer, Anja; Scheithauer, Heike; Wunderlich, Roland; Fietkau, Rainer; Gaipl, Udo (Advances in Experimental Medicine and Biology, 2016)
Radiotherapy (RT) predominantly is aimed to induce DNA damage in tumour cells that results in reduction of their clonogenicity and finally in tumour cell death. Adaptation of RT with higher single doses has become necessary and led to a more detailed view on what kind of tumour cell death is induced and which immunological consequences result from it. RT is capable of rendering tumour cells immunogenic by modifying the tumour cell phenotype and the microenvironment. Danger signals are released as well as the senescence-associated secretory phenotype. This results in maturation of dendritic cells and priming of cytotoxic T cells as well as in activation of natural killer cells. However, RT on the other hand can also result in immune suppressive events including apoptosis induction and foster tumour cell proliferation. That's why RT is nowadays increasingly combined with selected immunotherapies.
EVALuna2:18359

Can clinicopathological parameters predict for lymph node metastases in ypT0-2 rectal carcinoma? Results of the CAO/ARO/AIO-94 and CAO/ARO/AIO-04 phase 3 trials - Von Den Gruen, Jens Mueller; Hartmann, Arndt; Fietkau, Rainer; Ghadimi, Michael; Liersch, Torsten; Hohenberger, Werner; Weitz, Jurgen; Sauer, Rolf; Wittekind, Christian; Stroebel, Philipp; Roedel, Claus; Fokas, Emmanouil (Radiotherapy and Oncology, 2018)
BACKGROUND: The advent of less radical surgical approaches has generated concern about leaving locoregional lymph node metastases (LNM) unresected that could lead to adverse outcome. We examined the prognostic role of clinicopathological factors for ypN-positivity in patients with ypT0-2 rectal carcinoma treated within the CAO/ARO/AIO-94 and CAO/ARO/AIO-04 randomized phase 3 trials. METHODS: The correlation of clinicopathological factors with ypN-status (ypN0 vs ypN1/2) was examined in n = 776 patients with ypT0-2 rectal carcinoma after preoperative CRT and total mesorectal excision surgery using Pearson's Chi-squared test for categorical variables and Kruskal-Wallis' test for continuous variables. Multivariable analysis was performed using binary logistic regression to identify independent prognosticators for ypN-positivity. RESULTS: Residual LNM (ypN+) were found in 6%, 20.8% and 21.4% of patients with ypT0, ypT1 and ypT2 carcinomas, respectively. Independent prognosticators for LNM were advanced ypT category (p = 0.002) and lymphatic invasion (p = 0.020). In a separate multivariable analysis performed upon exclusion of ypT-category due to multicollinearity with residual tumor diameter (RTD), lymphatic invasion (p = 0.015) and RTD ≥10 mm (p = 0.005) demonstrated strong correlation with LNM. CONCLUSION: Advanced ypT-stage, lymphatic invasion and RTD ≥10 mm were prognostic factors for LNM in patients ypT0-2 rectal carcinoma treated with CRT and surgery within both phase 3 trials. The high incidence of LNM in the ypT1-2 group needs to be taken into consideration in the context of oncological safety and indicate that LE should be advocated with great caution in this patient subgroup. The prognostic pathological factor identified here could help guide decision of LE vs TME after standard CRT.
EVALuna2:34854

Can local excision be safely recommended in patients with ypT0-2 rectal cancer after chemoradiotherapy? Clinicopathological results of the CAO/ARO/AIO-94 and CAO/ARO/AIO-04 randomized phase 3 trials - Von Den Gruen, Mueller J.; Hartmann, Arndt; Fietkau, Rainer; Ghadimi, M.; Liersch, T.; Stroebel, P.; Sauer, Rolf; Roedel, C.; Fokas, E. (2018)
EVALuna2:36508

Can the documented patient briefing be carried out with an iPad App? - Schlechtweg, Philipp; Hammon, Matthias; Heberlein, Christian; Giese, David Andreas; Uder, Michael; Schwab, Siegfried (Journal of Digital Imaging, 2013)
To evaluate the feasibility of an iPad-based documented patient briefing for Magnetic Resonance Imaging (MRI) examinations. A standard briefing sheet and questionnaire for a MRI scan was converted from paper form into an iPad application. Twenty patients, who had been referred for an MRI scan, were briefed about the examination in paper form as well as via the iPad application before performing the MRI scan. Time each patient needed for the briefing and the number of questions that came up were documented. Patients' acceptance of the electronic briefing was assessed using a questionnaire. The mean processing time was 2.36 min (range 0.58 to 09.35 min., standard deviation ±2.05 min) for the paper-based briefing and 4.15 min (range 1.56 to 13.48 min, SD ± 2.36 min) for the app-based briefing. Concerning technical aspects, patients asked two questions during the app-based briefing; no questions arose during the paper-based briefing. Six patients preferred electronic briefing and four patients, the paper-based form. No patient preferred the electronic form with additional multimedial information. Eight participants did not mind which briefing version was used; two participants did not express their preference at all. Our experiences showed that electronic briefing using an iPad is feasible and has the potential to become a user-friendly alternative to the conventional paper-based approach. Owing to the broad range of the results, a follow-up study will seek to determine the influencing factors on processing time and other potential questions. © 2012 Society for Imaging Informatics in Medicine.
CRIS-Team Scopus Importer:2023-03-08
Keywords: App; Apple; Electronic patient consent; Feasibility; iPad; Tablet PC

Cardiac dose-sparing effects of deep-inspiration breath-hold in left breast irradiation : Is IMRT more beneficial than VMAT? - Sakka, Mazen; Kunzelmann, Leonie; Metzger, Martin; Grabenbauer, Gerhard (Strahlentherapie und Onkologie, 2017)
BACKGROUND: Given the reduction in death from breast cancer, as well as improvements in overall survival, adjuvant radiotherapy is considered the standard treatment for breast cancer. However, left-sided breast irradiation was associated with an increased rate of fatal cardiovascular events due to incidental irradiation of the heart. Recently, considerable efforts have been made to minimize cardiac toxicity of left-sided breast irradiation by new treatment methods such as deep-inspiration breath-hold (DIBH) and new radiation techniques, particularly intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT). The primary aim of this study was to evaluate the effect of DIBH irradiation on cardiac dose compared with free-breathing (FB) irradiation, while the secondary objective was to compare the advantages of IMRT versus VMAT plans in both the FB and the DIBH position for left-sided breast cancer. METHODS: In all, 25 consecutive left-sided breast cancer patients underwent CT simulation in the FB and DIBH position. Five patients were excluded with no cardiac displacement following DIBH-CT simulation. The other 20 patients were irradiated in the DIBH position using respiratory gating. Four different treatment plans were generated for each patient, an IMRT and a VMAT plan in the DIBH and in the FB position, respectively. The following parameters were used for plan comparison: dose to the heart, left anterior descending coronary artery (mean dose, maximum dose, D25% and D45%), ipsilateral, contralateral lung (mean dose, D20%, D30%) and contralateral breast (mean dose). The percentage in dose reduction for organs at risk achieved by DIBH for both IMRT and VMAT plans was calculated and compared for each patient by each treatment plan. RESULTS: DIBH irradiation significantly reduced mean dose to the heart and left anterior descending coronary artery (LADCA) using both IMRT (heart -20%; p = 0.0002, LADCA -9%; p = 0.001) and VMAT (heart -23%; p = 0.00003, LADCA -16%; p = 0.01) techniques as compared with FB radiation. There were no significant changes in left lung dose by IMRT; however, with VMAT planning, mean dose to the left lung was reduced by -4% (p = 0.0004). In addition, DIBH significantly increased the mean dose to the contralateral breast with IMRT (+14%, p = 0.002) and significantly reduced the dose to the contralateral breast with VMAT planning (-9%, p = 0.003) compared with the FB position. Additionally, in comparison with VMAT, the IMRT technique reduced mean heart dose both in the FB and the DIBH-position by -30% (p = 0.0004) and -26% (p = 0.002), respectively. Furthermore, IMRT increased the mean dose to the left lung in both the FB and the DIBH position (+5%, p = 0.003, p = 0.006), respectively. There were no significant changes in dose to the right lung and contralateral breast either in the FB or DIBH position between IMRT and VMAT techniques. CONCLUSION: Left-sided breast irradiation is best performed in the DIBH position, since a considerable dose sparing to the heart and LADCA can be achieved by using either IMRT or VMAT techniques. A significant additional decrease in heart and LADCA dose by IMRT in both FB and DIBH irradiation was seen compared with VMAT.
EVALuna2:36526

Cardiac MRI in Children and Adolescents Who Have Undergone Surgical Repair of Right-Sided Congenital Heart Disease: Automated Left Ventricular Volumes and Function Analysis and Effects of Different Manual Adjustments - Rompel, O.; Janka, Rolf Matthias; May, Matthias; Glöckler, Martin; Cesnjevar, Robert; Dittrich, Sven; Lell, Michael; Uder, Michael; Hammon, Matthias (Röfo-Fortschritte auf dem Gebiet der Röntgenstrahlen und der bildgebenden Verfahren, 2015)
Purpose: To evaluate automated segmentation and the effects of different manual adjustments regarding left ventricular parameter quantification in cardiac magnetic resonance (MR) data on children and adolescents who have undergone surgical repair of right-sided congenital heart disease (CHD). Materials and Methods: Dedicated software (syngo.via, Siemens AG) was used to automatically segment and/or manually adjust the end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), myocardial mass (MM) and ejection fraction (EF) before/after manual apex/base adjustment (ADJ-step 1) and after manual apex/base/myocardial contour adjustment (ADJ-step 2; reference standard). MR data of 40 patients (13.1 ± 3.1y, 4 - 17y) with repaired CHD with decreased pulmonary blood flow (CHD-DPBF) were evaluated. Intra- and inter-rater reliability was determined for 10 randomly selected patients. Results: The software correctly detected the left ventricle in 38/40 (95 %) patients. EDV after automated segmentation: 119.1 ± 44.0ml; after ADJ-step 1: 115.8 ± 39.5ml; after ADJ-step 2: 116.2 ± 39.4 ml. The corresponding results for ESV were 52.0 ± 18.5/49.6 ± 16.9/49.7 ± 16.4ml; for SV 67.1 ± 28.5/66.2 ± 25.4/66.5 ± 25.5ml; for EF 55.5 ± 7.3/56.7 ± 6.6/56.7 ± 6.3 %; for MM 83.7 ± 35.9/76.2 ± 28.3/74.6 ± 27.2 g. Significant differences were found for ESV/MM/EF comparing the automated segmentation results with these after ADJ-step 1 and ADJ-step 2. No significant differences were found when comparing all results of ADJ-step 1 and ADJ-step 2 or when comparing EDV/SV results. Intra- and inter-rater reliability was excellent. The mean time effort was 63.4 ± 6.9 s for the automated segmentation, 74.2 ± 8.9 s for ADJ-step 1 and 269.5 ± 39.4 s for ADJ-step 2. Conclusion: Automated left ventricular volumes and function analysis in children and adolescents with surgically treated CHD proved to be feasible with excellent intra- and inter-rater reliability. Automated segmentation with manual apex/base adjustment provided clinically acceptable results. Key Points: o?Automated left ventricular volume and function analysis in children and adolescents with surgically treated right-sided heart disease is feasible with excellent intra- and inter-rater reliability.o?Automated segmentation with manual apex/base adjustment provides clinically acceptable results.o?Additional manual myocardial contour adjustment does not significantly improve the results. Citation Format: o?Rompel O, Janka R, May MS et al. Cardiac MRI in Children and Adolescents Who Have Undergone Surgical Repair of Right-Sided Congenital Heart Disease: Automated Left Ventricular Volumes and Function Analysis and Effects of Different Manual Adjustments. Fortschr Röntgenstr 2015; 187: 1099 - 1107.
EVALuna2:14516

Carotid CTA: Radiation Exposure and Image Quality with the Use of Attenuation-Based, Automated Kilovolt Selection - Eller, A.; Wüst, Wolfgang; Kramer, Manuel; May, Matthias; Schmid, A.; Uder, Michael; Lell, Michael (American Journal of Neuroradiology, 2014)
CTA is considered the imaging modality of choice in evaluating the supraaortic vessels in many institutions, but radiation exposure remains a matter of concern. The objective of the study was to evaluate a fully automated, attenuation-based kilovolt selection algorithm in carotid CTA in respect to radiation dose and image quality compared with a standard 120-kV protocol.Ninety-eight patients were included: 53 examinations (patient age, 66 ± 12 years) were performed by use of automated adaption of tube potential (80-140 kV) on the basis of the attenuation profile of the scout scan (study group), and 45 examinations (patient age, 67 ± 11 years) were performed by use of a standard 120-kV protocol (control group). CT dose index volume and dose-length product were recorded from the examination protocol. Image quality was assessed by ROI measurements and calculations of SNR and contrast-to-noise ratio. Subjective image quality was evaluated by 2 observers with the use of a 4-point scale (3, excellent; 0, not diagnostic).Subjective image quality was rated as "excellent" or "good" in all examinations (study group, 2.8; control group, 2.8). The algorithm automatically selected 100 kV in 47% and 80 kV in 34%; 120 kV was retained in 19%. An elevation to 140 kV did not occur. Compared with the control group, overall CT dose index volume reduction was 33.7%; overall dose-length product reduction was 31.5%. In the low-kilovolt scans, image noise and mean attenuation of ROIs inside the carotid arteries were significantly higher than in 120-kV scans, resulting in a constant or increased (80-kV group) contrast-to-noise ratio.The attenuation-based, kilovolt selection algorithm enables a dose reduction of >30% in carotid artery CTA while maintaining contrast-to-noise ratio and subjective image quality at adequate levels.
EVALuna2:14326

Causes for the different Responses of Head and Neck Tumor and Normal Tissue Cell Lines to DNA-PK and mTor Inhibitors in Combination with ionizing Radiation - Klieber, N.; Fietkau, Rainer; Distel, Luitpold (STRAHLENTHERAPIE UND ONKOLOGIE, 2021)
CRIS-Team WoS Importer:2021-07-16

CBCT-based Detection and Analysis of the Positional Stability of implanted Gold Markers and Changes in the Shape of the Rectal Balloon during the Radiotherapy of the Prostate-Ca - Kallis, Karoline; Brandt, Tobias; Strnad, Vratislav; Lettmaier, S.; Fietkau, Rainer; Maier, Anne-Kathrin; Bert, Christoph (2017)
EVALuna2:32885

CD163+ M2c-like macrophages predominate in renal biopsies from patients with lupus nephritis - Olmes, Gregor; Buettner-Herold, Maike; Ferrazzi, Fulvia; Distel, Luitpold; Amann, Kerstin Ute; Daniel, Christoph (Arthritis Research & Therapy, 2015)
The role of macrophages in the pathogenesis of lupus nephritis, in particular their differentiation to a certain subtype (e.g., M1- or M2-like) modulating the inflammatory reaction, is unknown. Here we investigated whether the differentiation in M1- or M2-like macrophages depends on the stage of lupus nephritis and whether this correlates with clinical parameters.Using immunohistochemical analysis we analyzed renal biopsies from 68 patients with lupus nephritis (ISN/RPS classes II-V) for infiltration with M1-like (iNOS+/CD68+), M2a-like (CD206+/CD68+), M2c-like macrophages (CD163+/CD68+), and FoxP3+ regulatory T-cells. In addition, clinical parameters at the time of renal biopsy, i.e., blood pressure, proteinuria and serum urea were correlated with the macrophage infiltration using the Spearman test.The mean number of CD68+ macrophages was related to the diagnosed ISN/RPS class, showing the highest macrophage infiltration in biopsies with diffuse class IV and the lowest number in ISN/RPS class V. In all ISN/RPS classes we detected more M2c-like CD163+/CD68+ than M2a-like CD206+/CD68+ cells, while M1-macrophages played only a minor role. Cluster analysis using macrophage subtype numbers in different renal compartments revealed three main clusters showing cluster 1 dominated by class V. Clusters 2 and 3 were dominated by lupus class IV indicating that this class can be further differentiated by its macrophage population. The number of tubulointerstitial FoxP3+ cells correlated with all investigated macrophage subtypes showing the strongest association to numbers of M2a-like macrophages. Kidney function, as assessed by serum creatinine and serum urea, correlated positively with the number of total CD68+, M2a-like and M2c-like macrophages in the tubulointerstitium. In addition, total CD68+ and M2c-like macrophage numbers highly correlated with Austin activity score. Interestingly, in hypertensive lupus patients only the number of M2a-like macrophages was significantly increased compared to biopsies from normotensive lupus patients.M2-like macrophages are the dominant subpopulation in human lupus nephritis and particularly, M2a subpopulations were associated with disease progression, but their role in disease progression remains unclear.
EVALuna2:9308

CD8+and Regulatory T cells Differentiate Tumor Immune Phenotypes and Predict Survival in Locally Advanced Head and Neck Cancer - Echarti, Alessia; Hecht, Markus; Büttner-Herold, Maike; Haderlein, Marlen; Hartmann, Arndt; Fietkau, Rainer; Distel, Luitpold (Cancers, 2019)
Background: The tumor immune status "inflamed", "immune excluded", and "desert" might serve as a predictive parameter. We studied these three cancer immune phenotypes while using a simple immunohistochemical algorithm. Methods: Pre-treatment tissue samples of 280 patients with locally advanced HNSCC treated with radiochemotherapy were analyzed. A double staining of CD8+ cytotoxic T cells (CTL) and FoxP3+ (Treg) was performed and the cell density was evaluated in the intraepithelial and stromal compartment of the tumor. Results: The classification of tumors as "immune desert" when stromal CTL were <= 50 cells/mm(2), "inflamed" when intraepithelial CTL were > 500 cells/mm(2), and as "excluded" when neither of these definitions met these cut off values allowed the best discrimination regarding overall survival. These groups had median OS periods of 37, 61, and 85 months, respectively. In "immune desert" and "immune excluded" tumors high Treg tended to worsen OS, but in "inflamed" tumors high Treg clearly improved OS. Conclusions: We propose that, in locally advanced HNSCC, the tumor immune state "inflamed", "immune excluded", and "immune desert" can be defined by intraepithelial and stromal CTL. Tregs can further subdivide these groups. The opposing effects of Tregs in the different groups might be the reason for the inconsistency of Tregs prognostic values published earlier.
CRIS-Team WoS Importer:2019-10-25

Cell-Cannibalism by Normal Tissue Cells as a Survival Benefit after Irradiation of Normal Tissue Cells leads to an Increase in their Activity as non-professional Phagocytes - Sonntag, T.; Distel, Luitpold; Fietkau, Rainer (STRAHLENTHERAPIE UND ONKOLOGIE, 2021)
CRIS-Team WoS Importer:2021-07-16

Cell-in-cell phenomenon: leukocyte engulfment by non-tumorigenic cells and cancer cell lines - Bauer, Mareike; Hader, Michael; Hecht, Markus; Büttner-Herold, Maike; Fietkau, Rainer; Distel, Luitpold (BMC Molecular and Cell Biology, 2021)
Background Research on cell-in-cell (CIC) phenomena, including entosis, emperipolesis and cannibalism, and their biological implications has increased in recent years. Homotypic and heterotypic engulfment of various target cells by numerous types of host cells has been studied in vitro and in tissue sections. This work has identified proteins involved in the mechanism and uncovered evidence for CIC as a potential histopathologic predictive and prognostic marker in cancer. Our experimental study focused on non-professional phagocytosis of leukocytes. Results We studied the engulfment of peripheral blood mononuclear cells isolated from healthy donors by counting CIC structures. Two non-tumorigenic cell lines (BEAS-2B, SBLF-9) and two tumour cell lines (BxPC3, ICNI) served as host cells. Immune cells were live-stained and either directly co-incubated or treated with irradiation or with conventional or microwave hyperthermia. Prior to co-incubation, we determined leukocyte viability for each batch via Annexin V-FITC/propidium iodide staining. All host cells engulfed their targets, with uptake rates ranging from 1.0% +/- 0.5% in BxPC3 to 8.1% +/- 5.0% in BEAS-2B. Engulfment rates of the cancer cell lines BxPC3 and ICNI (1.6% +/- 0.2%) were similar to those of the primary fibroblasts SBLF-9 (1.4% +/- 0.2%). We found a significant negative correlation between leukocyte viability and cell-in-cell formation rates. The engulfment rate rose when we increased the dose of radiotherapy and prolonged the impact time. Further, microwave hyperthermia induced higher leukocyte uptake than conventional hyperthermia. Using fluorescent immunocytochemistry to descriptively study the proteins involved, we detected ring-like formations of diverse proteins around the leukocytes, consisting, among others, of alpha-tubulin, integrin, myosin, F-actin, and vinculin. These results suggest the involvement of actomyosin contraction, cell-cell adhesion, and the alpha-tubulin cytoskeleton in the engulfment process. Conclusions Both non-tumorigenic and cancer cells can form heterotypic CIC structures by engulfing leukocytes. Decreased viability and changes caused by microwave and X-ray irradiation trigger non-professional phagocytosis.
CRIS-Team WoS Importer:2021-08-13

Cell-in-cell structures are more potent predictors of outcome than senescence or apoptosis in head and neck squamous cell carcinomas - Schenker, Hannah; Buettner-Herold, Maike; Fietkau, Rainer; Distel, Luitpold (Radiation Oncology, 2017)
This study sheds light on cell inactivating processes with focus on the phenomenon of cell-in-cell (CIC). Cell-in-cell describes a cell process where one cell is being engulfed by another non-professional phagocyte. We determined frequency and prognostic impact of CIC structures (CICs) as well as of senescent and apoptotic cells in head and neck squamous cell carcinomas (HNSCC).These different forms of cell inactivation as well as the proportion of proliferating and tumor cells were assessed in 169 pre-radiochemotherapy biopsies and 32 post-therapy tumor resections by immunohistochemistry of tissue microarrays. Four consecutive cancer sections were stained with antibodies specific for E-cadherin for CIC detection, cleaved caspase-3 for apoptosis, H3K9Me for senescence and Ki67 as a proliferation marker. Positive events were quantified in corresponding tumor areas.CICs were found in 55.5%, senescent cells in 67.1% and apoptotic cells in 93.3% of samples. While no prognostic impact of apoptotic and senescent cells was observed, CICs turned out to significantly influence overall-survival (p = 0.016) with a lack of CICs being prognostically beneficial. There was no correlation between CICs and apoptosis and 98.9% of CICs were negative for cleaved caspase-3.CIC formation is a frequent event in HNSCC and a superior predictive marker compared to senescence and apoptosis. Independence of CIC and apoptosis and the adverse prognosis associated with numerous CICs lead to the assumption that CICs might take up necrotic rather than apoptotic cells preventing an adequate antitumoral immune response that would otherwise be initiated by necrotic cells through damage-associated molecular pattern molecules.
EVALuna2:25527

Cell-In-Cell Structures in Early Breast Cancer Are Prognostically Valuable - Bauer, Mareike; Hildebrand, Laura; Rosahl, Marie Charlotte; Erber, Ramona; Schnellhardt, Sören; Büttner-Herold, Maike; Putz, Florian; Ott, Oliver; Hack, Caroline; Fietkau, Rainer; Distel, Luitpold (Cells, 2023)
Cell-in-cell (CIC) structures in breast cancer have so far been studied in a small inhomogeneous patient population, suggesting the prognostic importance of CIC. In the present study, we focused on CIC in early hormone-sensitive breast cancer. With in vitro co-culture experiments, we compared the homotypic phagocytic capacity of two breast cancer cell lines to that of primary human fibroblasts. Afterward, we studied 601 tissue specimens from 147 patients participating in an institutional accelerated partial breast irradiation (APBI) phase II trial. Both breast cancer cell lines performed non-professional phagocytosis at a higher rate than primary human fibroblasts. In this study cohort, 93.2% of the patients had T1 tumours, and 6.8% had T2 tumours. CIC was found in 61.2% of the patients, with a CIC rate ranging from <1/mm2 to 556.5/mm2 with a mean of 30.9/mm2 ± 68.4/mm2. CIC structures were prognostically favourable for local recurrence-free survival and disease-free survival. Regarding metastasis-free survival, CIC-positive patients had an unfavourable prognosis. Subgroup analysis indicated a correlation between a high proliferation index and high CIC rates. CIC had the highest prognostic value in young breast cancer patients (p = 0.004). With this study, we provide further evidence of CIC as a prognostic marker in breast cancer.
CRIS-Team Scopus Importer:2023-01-20
Keywords: accelerated partial breast irradiation; breast cancer; cell-in-cell; ionizing radiation; non-professional phagocytosis; radiotherapy

Cell-to-cell distances between tumor-infiltrating inflammatory cells have the potential to distinguish functionally active from suppressed inflammatory cells - Nagl, Sandra; Haas, M.; Lahmer, Godehard; Buettner-Herold, M.; Grabenbauer, Gerhard; Fietkau, Rainer; Distel, Luitpold (OncoImmunology, 2016)
Beyond their mere presence, the distribution pattern of inflammatory cells is of special interest. Our hypothesis was that random distribution may be a clear indicator of being non-functional as a consequence of lack of interaction. Here, we have assessed the implication of cell-to-cell distances among inflammatory cells in anal squamous cell carcinoma and a possible association with survival data. Thirty-eight patients suffering from anal carcinoma were studied using tissue microarrays, double staining immunohistochemistry, whole slide scanning and image analysis software. Therapy consisted of concurrent radiochemotherapy. Numbers of stromal and intraepithelial tumor-infiltrating inflammatory cells (TIC) and the distances between cells were quantified. Double-staining of FoxP3(+) cells with either CD8(+), CD1a(+) or CD20(+) cells was performed. Measured cell-to-cell distances were compared to computer simulated cell-to-cell distances leading to the assumption of non-randomly distributed and therefore functional immune cells. Intraepithelial CD1a(+) and CD20(+) cells were randomly distributed and therefore regarded as non-functional. In contrary, stromal CD20(+) cells had a non-random distribution pattern. A non-random distance between CD20(+) and FoxP3(+) cells was associated with a clearly unfavorable outcome. Measured distances between FoxP3(+) cells were distinctly shorter than expected and indicate a functional active state of the regulatory T cells (Treg). Analysis of cell-to-cell distances between TIC has the potential to distinguish between suppressed non-functional and functionally active inflammatory cells. We conclude that in this tumor model most of the CD1a(+) cells are non-functional as are the intraepithelial CD20(+) cells, while stromal CD20(+) cells and FoxP3(+) cells are functional cells.
EVALuna2:18358

Central pulse pressure predicts BP reduction after renal denervation in patients with treatment-resistant hypertension - Ott, Christian; Schmid, Axel; Toennes, Stefan W.; Ditting, Tilmann; Veelken, Roland; Uder, Michael; Schmieder, Roland (EuroIntervention, 2015)
Enhanced vascular ageing is associated with elevated central pulse pressure (cPP), an independent predictor of cardiovascular (CV) events. Although antihypertensive treatment strategies are effective, high residual CV risk remains indicative of advanced and largely irreversible vascular damage. Renal denervation (RDN) has been shown to reduce blood pressure (BP) to various extents in patients with treatment-resistant hypertension (TRH). We hypothesised that cPP predicts BP reduction after RDN.Sixty-three patients with true TRH underwent catheter-based RDN using the Symplicity Flex(TM) catheter and were followed for six months. At baseline, cPP was assessed by pulse wave analysis (SphygmoCor(TM)). Patients were stratified according to their median cPP (55 mmHg), and called "low cPP" (below the median) or "high cPP" (above the median). Office BP reduction six months after RDN was greater (-22±19/-13±11 vs. -12±20/-5±13 mmHg, p=0.038/0.014) and 24-hr ambulatory blood pressure (ABP) reduction tended to be greater (-11±13/-8±10 vs. -3±18/-4±10 mmHg, p=0.070/0.112) in patients with low cPP compared to those with high cPP. Only cPP (?=0.687, p=0.001) and baseline systolic BP (?=-0.564, p<0.001) were independent determinants of office systolic BP reduction after RDN.Our data suggest that cPP, indicative of the degree of large arterial stiffening, may be helpful to identify responders to RDN.
EVALuna2:3764

Cetuximab, fluorouracil and cisplatin with or without docetaxel for patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (CeFCiD): an open-label phase II randomised trial (AIO/IAG-KHT trial 1108) - Klinghammer, K.; Gauler, T.; Dietz, A.; Grünwald, V.; Stöhlmacher, J.; Knipping, S.; Schroeder, M.; Guntinas-Lichius, O.; Frickhofen, N.; Lindeman, H. W.; Fietkau, Rainer; Haxel, B.; et al. (European Journal of Cancer, 2019)
Background: The combination of cisplatin, 5-fluorouracil (5-FU) and cetuximab (PFC) is the reference first-line treatment for recurrent/metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN). We analysed whether treatment intensification by the addition of docetaxel to PFC improved efficacy in R/M SCCHN. Methods: A total of 180 patients with R/M SCCHN (1:1) were assigned to receive either cisplatin (40 mg/m2), docetaxel (40 mg/m2) and 5-FU (2000 mg/m2) at days 1 and 8 and cetuximab (400/250 mg/m2) at days 1, 8 and 15 (DPFC) or standard cisplatin (100 mg/m2) at day 1, 5-FU (1000 mg/m2) at days 1–4 and cetuximab (400/250 mg/m2) at days 1, 8 and 15 (PFC). Chemotherapy was repeated every 21 days and continued for a maximum of 6 cycles in absence of disease progression or limiting toxicity, followed by cetuximab maintenance (500 mg/m2 every 2 weeks). The primary end-point was progression-free survival (PFS). Results: A preplanned interim analysis for toxicity after 20 patients/arm revealed excessive grade 3 and 4 gastrointestinal (65%) and infectious toxicities (35%) in arm A, which led to dose reduction of cisplatin to 30 mg/m2 and 5-FU to 1000 mg/m2 for subsequent patients. With a median follow-up of 2 years, grade 4 toxicities were 21.3% vs. 30.8% for DPFC and PFC, respectively. More treatment-related deaths occurred with DPFC vs. PFC, with 11.2% and 6.6%, respectively. For DPFC and PFC, the median PFS was 6.3 vs. 6.4 months (hazard ratio [HR] = 0.97, p = 0.87), the median overall survival was 8.9 vs. 10.6 months (HR = 1.29 p = 0.1) and response rates were 38.2% vs. 31.9% (p = 0.9), respectively. Conclusions: DPFC failed to improve efficacy in R/M SCCHN. On the contrary, a high toxicity and mortality rate was detected in both arms, which underscores the vulnerability of patients with R/M SCCHN, and research on the need for further optimisation of the front-line chemotherapy backbone is ongoing.
CRIS-Team Scopus Importer:2019-10-18
Keywords: Cetuximab; Chemotherapy; Docetaxel; Head and neck cancer; Randomised trial

Cetuximab in combination with platinum-based chemotherapy or radiotherapy in patients with recurrent and/or metastatic SSCHN in clinical routine: Updated interim results of the prospective SOCCER study - Hecht, Markus; Hahn, D.; Wolber, P.; Hautmann, M.; Reichert, D.; Weniger, J.; Belka, C.; Bergmann, T.; Goehler, T.; Welslau, M. K.; Hofmann, D.; Fietkau, Rainer (ANNALS OF ONCOLOGY, 2018)
CRIS-Team WoS Importer:2019-03-08

Cetuximab in combination with platinum-based chemotherapy or radiotherapy in recurent and/or metastatic SCCHN in a non-selected patient cohort (interim analysis of the phase IV SOCCER trial) - Hecht, Markus; Hahn, D.; Beutner, D.; Reichert, D.; Goehler, T.; Wurm, R.; Welslau, M.; Renziehausen, L.; Balermpas, P.; Bergmann, T.; Assmann, M.; Belka, C.; et al. (2016)
EVALuna2:32919

Cetuximab in combination with platinum-based chemotherapy or radiotherapy in recurent and/or metastatic SCCHN in a non-selected patient cohort (interim analysis of the phase IV SOCCER trial) - Hecht, Markus; Hahn, D.; Beutner, D.; Reichert, D.; Goehler, T.; Wurm, R.; Welslau, M.; Renziehausen, L.; Balermpas, P.; Bergmann, T.; Assmann, M.; Belka, C.; et al. (2016)
EVALuna2:32920

Challenges of radiotherapy: report on the 4D treatment planning workshop 2013 - Knopf, Antje; Nill, Simeon; Yohannes, Indra; Graeff, Christian; Dowdell, Stephen; Kurz, Christopher; Sonke, Jan-Jakob; Biegun, Aleksandra K.; Lang, Stephanie; Mcclelland, Jamie; Champion, Benjamin; Fast, Martin; et al. (Physica Medica, 2014)
This report, compiled by experts on the treatment of mobile targets with advanced radiotherapy, summarizes the main conclusions and innovations achieved during the 4D treatment planning workshop 2013. This annual workshop focuses on research aiming to advance 4D radiotherapy treatments, including all critical aspects of time resolved delivery, such as in-room imaging, motion detection, motion managing, beam application, and quality assurance techniques. The report aims to revise achievements in the field and to discuss remaining challenges and potential solutions. As main achievements advances in the development of a standardized 4D phantom and in the area of 4D-treatment plan optimization were identified. Furthermore, it was noticed that MR imaging gains importance and high interest for sequential 4DCT/MR data sets was expressed, which represents a general trend of the field towards data covering a longer time period of motion. A new point of attention was work related to dose reconstructions, which may play a major role in verification of 4D treatment deliveries. The experimental validation of results achieved by 4D treatment planning and the systematic evaluation of different deformable image registration methods especially for inter-modality fusions were identified as major remaining challenges. A challenge that was also suggested as focus for future 4D workshops was the adaptation of image guidance approaches from conventional radiotherapy into particle therapy. Besides summarizing the last workshop, the authors also want to point out new evolving demands and give an outlook on the focus of the next workshop.
EVALuna2:18242

Change in the radio-oncological Treatment Concept for Brain Metastases through a dedicated Radiotherapy Planning MRI - Voigt, R.; Masitho, Siti; Grigo, Johanna; Reissig, L.; Uder, Michael; Semrau, Sabine; Fietkau, Rainer; Bert, Christoph; Putz, Florian (STRAHLENTHERAPIE UND ONKOLOGIE, 2022)
CRIS-Team WoS Importer:2022-06-03

Characteristics of the first 615 patients enrolled in Pacific R: A study of the first real-world data on unresectable stage III NSCLC patients treated with durvalumab after chemoradiotherapy - Girard, N.; Fietkau, Rainer; Garassino, M.; Garrido, Pilar; Field, J. K.; Peters, S.; Smit, H. J. M.; Perol, M.; Merle, P.; Sibille, A.; Markman, B.; Bouchaab, H.; et al. (ANNALS OF ONCOLOGY, 2020)
CRIS-Team WoS Importer:2020-10-30

Checkpoint inhibitors and radiation treatment in Hodgkin's lymphoma : New study concepts of the German Hodgkin Study Group - Baues, C.; Semrau, Robert; Gaipl, Udo; Broeckelmann, P. J.; Rosenbrock, J.; Engert, A.; Marnitz, S. (Strahlentherapie und Onkologie, 2017)
BACKGROUND: Patients with classical Hodgkin's lymphoma (cHL) have a good prognosis even in advanced stages. However, combined chemo- and radiotherapy, as the standard of care, is also associated with treatment-related toxicities such as organ damage, secondary neoplasias, infertility, or fatigue and long-term fatigue. Many patients suffer from this burden although their cHL was cured. Therefore, the efficacy of immune checkpoint inhibitors like anti-PD1/PD-L1 antibodies in the treatment of solid cancers and also in HL offers new options. A remarkable and durable response rate with a favorable toxicity profile was observed in heavily pretreated cHL patients. METHODS: Planning to perform prospective randomized clinical trials in the content of radio-immune treatment in patients with Hodgkin's lymphoma (HL), we transferred the results of preliminary clinical studies and basic research in clinical relevant study concepts. RESULTS: Based on these promising early phase trial data, the German Hodgkin Study Group (GHSG) will investigate innovative treatment regimens in upcoming phase II trials. CONCLUSION: The therapeutic efficacy and potential synergies of anti-PD1 antibodies in combination with chemo- or radiotherapy will be investigated in various settings of HL.
EVALuna2:32931

Chemoradiation Increases PD-L1 Expression in Certain Melanoma and Glioblastoma Cells - Derer, Anja; Spiljar, Martina; Baeumler, Monika; Hecht, Markus; Fietkau, Rainer; Frey, Benjamin; Gaipl, Udo (Frontiers in Immunology, 2016)
Immunotherapy approaches currently make their way into the clinics to improve the outcome of standard radiochemotherapy (RCT). The programed cell death receptor ligand 1 (PD-L1) is one possible target that, upon blockade, allows T cell-dependent antitumor immune responses to be executed. To date, it is unclear which RCT protocol and which fractionation scheme leads to increased PD-L1 expression and thereby renders blockade of this immune suppressive pathway reasonable. We therefore investigated the impact of radiotherapy (RT), chemotherapy (CT), and RCT on PD-L1 surface expression on tumor cells of tumor entities with differing somatic mutation prevalence. Murine melanoma (B16-F10), glioblastoma (GL261-luc2), and colorectal (CT26) tumor cells were treated with dacarbazine, temozolomide, and a combination of irinotecan, oxaliplatin, and fluorouracil, respectively. Additionally, they were irradiated with a single dose [10 Gray (Gy)] or hypo-fractionated (2 × 5 Gy), respectively, norm-fractionated (5 × 2 Gy) radiation protocols were used. PD-L1 surface and intracellular interferon (IFN)-gamma expression was measured by flow cytometry, and IL-6 release was determined by ELISA. Furthermore, tumor cell death was monitored by AnnexinV-FITC/7-AAD staining. For firstin vivoanalyses, the B16-F10 mouse melanoma model was chosen. In B16-F10 and GL261-luc2 cells, particularly norm-fractionated and hypo-fractionated radiation led to a significant increase of surface PD-L1, which could not be observed in CT26 cells. Furthermore, PD-L1 expression is more pronounced on vital tumor cells and goes along with increased levels of IFN-gamma in the tumor cells. In melanoma cells CT was the main trigger for IL-6 release, while in glioblastoma cells it was norm-fractionated RT.In vivo, fractionated RT only in combination with dacarbazine induced PD-L1 expression on melanoma cells. Our results suggest a tumor cell-mediated upregulation of PD-L1 expression following in particular chemoradiation that is not only dependent on the somatic mutation prevalence of the tumor entity.
EVALuna2:32917
Keywords: fractionated radiotherapy; immunotherapy; checkpoint inhibitor; PD-L1; IFN-gamma; IL-6; melanoma; glioblastoma

Chemoradiotherapy plus hyperthermia (CRTH) versus chemoradiotherapy (CRT) alone in neoadjuvant treatment of soft tissue sarcoma: tumor response, treatment toxicity and disease control - Willner, Alexander; Agaimy, Abbas; Fechner, Katja; Ott, Oliver; Denz, Axel; Weissmann, Thomas; Meidenbauer, Norbert; Höfler, Daniel; Gaipl, Udo; Frey, Benjamin; Schmidt, Manfred; Haller, Florian; et al. (International Journal of Hyperthermia, 2023)
Introduction: Neoadjuvant chemotherapy and radiotherapy for the management of soft tissue sarcomas (STS) are still preferably delivered sequentially, with or without concurrent hyperthermia. Concurrent delivery of chemo-, radio- and thermotherapy may produce synergistic effects and reduce chemotherapy-free intervals. The few available studies suggest that concurrent chemoradiation (CRT) has a greater local effect. Data on the efficacy and toxicity of adding hyperthermia to CRT (CRTH) are sparse. Materials and methods: A cohort of 101 patients with STS of the extremities and trunk who received CRT (n = 33) or CRTH (n = 68) before resection of macroscopic tumor (CRT: n = 19, CRTH: n = 49) or re-resection following a non-oncological resection, so called ‘whoops procedure’, (CRT: n = 14, CRTH: n = 19) were included in this retrospective study. CRT consisted of two cycles of doxorubicine (50 mg/m2 on d2) plus ifosfamide (1500 mg/m2 on d1-5, q28) plus radiation doses of up to 60 Gy. Hyperthermia was delivered in two sessions per week. Results: All patients received the minimum dose of 50 Gy. Median doses of ifosfamide and doxorubicin were comparable between CRT (75%/95%) and CRTH (78%/97%). The median number of hyperthermia sessions was seven. There were no differences in acute toxicities. Major wound complications occurred in 15% (CRT) vs. 25% (CRTH) (p = 0.19). In patients with macroscopic disease, the addition of hyperthermia resulted in a tendency toward improved remission: regression ≥90% occurred in 21/48 (CRTH) vs. 4/18 (CRT) patients (p = 0.197). With a median postoperative follow-up of 72 months, 6-year local control and overall survival rates for CRTH vs. CRT alone were 85 vs. 78% (p = 0.938) and 79 vs. 71% (p = 0.215). Conclusions: Both CRT and CRTH are well tolerated with an expected rate of wound complications. The results suggest that adding hyperthermia may improve tumor response.
CRIS-Team Scopus Importer:2023-09-01
Keywords: chemoradiotherapy; chemotherapy; hyperthermia; neoadjuvant; radiotherapy; Sarcoma; soft-tissue sarcoma; toxicity

Chemoradiotherapy plus induction or consolidation chemotherapy as total neoadjuvant therapy for locally advanced rectal cancer: Final results of the CAO/ARO/AIO-12 randomized phase 2 trial - Fokas, E.; Schlenska-Lange, A.; Polat, B.; Klautke, G.; Grabenbauer, G.; Fietkau, Rainer; Kuhnt, T.; Staib, L.; Brunner, T.; Grosu, A. -L.; Kirste, S.; Jacobasch, L.; et al. (STRAHLENTHERAPIE UND ONKOLOGIE, 2021)
CRIS-Team WoS Importer:2021-07-16

Chemoradiotherapy Plus Induction or Consolidation Chemotherapy as Total Neoadjuvant Therapy for Patients With Locally Advanced Rectal Cancer Long-term Results of the CAO/ARO/AIO-12 Randomized Clinical Trial - Fokas, Emmanouil; Schlenska-Lange, Anke; Polat, Buelent; Klautke, Gunther; Grabenbauer, Gerhard G.; Fietkau, Rainer; Kuhnt, Thomas; Staib, Ludger; Brunner, Thomas; Grosu, Anca-Ligia; Kirste, Simon; Jacobasch, Lutz; et al. (JAMA Oncology, 2021)
IMPORTANCE Total neoadjuvant therapy has been increasingly adopted for multimodal rectal cancer treatment. The optimal sequence of chemoradiotherapy (CRT) and chemotherapy needs to be established.
CRIS-Team WoS Importer:2021-12-10

Chemoradiotherapy plus induction versus consolidation chemotherapy as total neoadjuvant therapy for locally advanced rectal cancer: results of the German CAO/ARO/AIO-12 multicentre, open-label, randomised, phase 2 trial - Fokas, E.; Allgaeuer, M.; Polat, B.; Klautke, G.; Grabenbauer, G.; Fietkau, Rainer; Kuhnt, T.; Staib, L.; Brunner, T.; Grosu, A-L; Schmiegel, W.; Jacobasch, L.; et al. (STRAHLENTHERAPIE UND ONKOLOGIE, 2019)
CRIS-Team WoS Importer:2019-06-07

Chemoradiotherapy with and without deep regional hyperthermia for squamous cell carcinoma of the anus - Ott, Oliver J.; Schmidt, Manfred; Semrau, Sabine; Strnad, Vratislav; Matzel, Klaus E.; Schneider, Ignaz Hans Friedrich; Raptis, Dimitrios; Uter, Wolfgang; Grützmann, Robert; Fietkau, Rainer (Strahlentherapie und Onkologie, 2018)
PURPOSE: To compare results after chemoradiotherapy with and without deep regional hyperthermia in patients with anal cancer. METHODS: Between 2000 and 2015, a total of 112 consecutive patients with UICC stage I-IV anal cancer received chemoradiotherapy with 5‑fluororuracil and mitomycin C (CRT). In case of insufficient tumor response 4-6 weeks after chemoradiotherapy, patients received an interstitial pulsed-dose-rate brachytherapy boost. Additionally, 50/112 patients received hyperthermia treatments (HCRT). RESULTS: Median follow-up was 41 (2-165) months. After 5 years follow-up, overall (95.8 vs. 74.5%, P = 0.045), disease-free (89.1 vs. 70.4%, P = 0.027), local recurrence-free (97.7 vs. 78.7%, P = 0.006), and colostomy-free survival rates (87.7 vs. 69.0%, P = 0.016) were better for the HCRT group. Disease-specific, regional failure-free, and distant metastasis-free survival rates showed no significant differences. The adjusted hazard ratios for death were 0.25 (95% CI, 0.07 to 0.92; P = 0.036) and for local recurrence 0.14 (95% CI, 0.02 to 1.09; P = 0.06), respectively. Grades 3-4 early toxicities were comparable with the exception of hematotoxicity, which was higher in the HCRT group (66 vs. 43%, P = 0.032). Incidences of late side effects were similar with the exception of a higher telangiectasia rate in the HCRT group (38.0 vs. 16.1%, P = 0.009). CONCLUSION: Additional regional hyperthermia improved overall survival, local control, and colostomy rates. Its potential beneficial role has to be confirmed in a prospective randomized setting. Therefore, the HyCAN trial has already been established by our group and is currently recruiting patients (Clinicaltrials.gov identifier: NCT02369939).
EVALuna2:36451

Chemoradiotherapy with and without deep regional hyperthermia for squamous cell carcinoma of the anus - Ott, O. J.; Schmidt, M.; Semrau, S.; Strnad, Vratislav; Matzel, K. E.; Schneider, I.; Raptis, D.; Uter, Wolfgang; Grützmann, Robert; Fietkau, Rainer (STRAHLENTHERAPIE UND ONKOLOGIE, 2019)
CRIS-Team WoS Importer:2019-06-07

Chemo-RT plus induction or consolidation chemotherapy for rectal cancer: a randomised phase 2 trial - Fokas, E.; Allgaeuer, M.; Polat, B.; Klautke, G.; Grabenbauer, G.; Fietkau, Rainer; Kuhnt, T.; Staib, L.; Brunner, T.; Grosu, A. L.; Schmiegel, W.; Jacobasch, L.; et al. (RADIOTHERAPY AND ONCOLOGY, 2019)
CRIS-Team WoS Importer:2019-06-18

Choosing a reference phase for a dynamic tumor tracking treatment: A new degree of freedom? - Ziegler, Marc; Lettmaier, Sebastian; Fietkau, Rainer; Bert, Christoph (Medical Physics, 2019)
Purpose: With the introduction of dynamic tumor tracking in radiotherapy, it is possible to irradiate moving targets with minimal safety margins. However, most dynamic tumor tracking techniques rely on changing the beam geometry by, for example, adapting the multileaf collimator (MLC) positions or rotating the LINAC head. These changes are relative to a reference position which is determined by a specific breathing phase. Since these changes in the beam path also influence the delivered dose, choosing a different reference position based on a different breathing phase impacts the applied dose to the patient. This work investigates the influence of choosing different reference breathing phases on the dose distribution. Methods: The Vero system tracks the moving target by performing a pan and tilt rotation of the LINAC head. For 13 patients, the target position was extracted from every phase of a four-dimensional computed tomography (4DCT) and the pan and tilt values were determined with respect to three different reference phases. These reference phases were inspiration, expiration, and the midventilation. For all reference phases, a 4D dose calculation was performed on the 4DCT regarding the respective pan and tilt values. Furthermore, the applied dose to the target and surrounding organs at risk was calculated. To accumulate the dose distribution, weights from the actual patient breathing motion were determined. The weights were calculated from the breathing motions from different days to investigate the impact of daily variations in the breathing motion onto the accumulated dose distribution. All obtained values were then compared to the static treatment plan. Results: The mean and maximum doses applied to the target or surrounding organs at risk show no general behavior depending on the different reference phases. Nevertheless, for some patients, large differences (approx. 30%) in the applied dose to certain organs at risk could be observed, whereas the applied dose to the target shows no dependency on the different reference phases. However, the mean target dose is in all cases approx. 1.5% below the reference value from the static treatment plan. Conclusion: Although no general dependency of the applied dose on the selected reference phase could be found, the choice of the reference phase can have great impact on the organ at risk dose for some patients. Thus, the choice of the reference phase used for patient positioning should be considered during treatment planning since it can be seen as a new degree of freedom of a treatment based on tracking.
CRIS-Team Scopus Importer:2019-07-16
Keywords: 4D dose calculation; dynamic tumor tracking; liver cancer; lung cancer

Chromosomal radiosensitivity in oncological and non-oncological patients with rheumatoid arthritis and connective tissue diseases - Rzepka, Dinah; Schenker, Hannah; Geinitz, Hans; Silberberger, Elisabeth; Kaudewitz, Dorothee; Schuster, Barbara; Kuhlmann, Lukas; Schonath, Miriam; Ayala Gaona, Horacio; Aschacher, Bernhard; Fietkau, Rainer; Schett, Georg; et al. (Radiation Oncology, 2023)
Background: The risk of developing late radiotoxicity after radiotherapy in patients with high chromosomal radiosensitivity after radiotherapy could potentially be higher compared to the risk in patients with average radiosensitivity. In case of extremely high radiosensitivity, dose reduction may be appropriate. Some rheumatic diseases (RhD), including connective tissue diseases (CTDs) appear to be associated with higher radiosensitivity. The question arises as to whether patients with rheumatoid arthritis (RA) also generally have a higher radiosensitivity and whether certain parameters could indicate clues to high radiosensitivity in RA patients which would then need to be further assessed before radiotherapy. Methods: Radiosensitivity was determined in 136 oncological patients with RhD, 44 of whom were RA patients, and additionally in 34 non-oncological RA patients by three-colour fluorescence in situ hybridization (FiSH), in which lymphocyte chromosomes isolated from peripheral blood are analysed for their chromosomal aberrations of an unirradiated and an with 2 Gy irradiated blood sample. The chromosomal radiosensitivity was determined by the average number of breaks per metaphase. In addition, correlations between certain RA- or RhD-relevant disease parameters or clinical features such as the disease activity score 28 and radiosensitivity were assessed. Results: Some oncological patients with RhD, especially those with connective tissue diseases have significantly higher radiosensitivity compared with oncology patients without RhD. In contrast, the mean radiosensitivity of the oncological patients with RA and other RhD and the non-oncological RA did not differ. 14 of the 44 examined oncological RA-patients (31.8%) had a high radiosensitivity which is defined as ≥ 0.5 breaks per metaphase. No correlation of laboratory parameters with radiosensitivity could be established. Conclusions: It would be recommended to perform radiosensitivity testing in patients with connective tissue diseases in general. We did not find a higher radiosensitivity in RA patients. In the group of RA patients with an oncological disease, a higher percentage of patients showed higher radiosensitivity, although the average radiosensitivity was not high.
CRIS-Team Scopus Importer:2023-06-16
Keywords: Chromosomal aberrations; Collagen vascular disease; Connective tissue disease; Fluorescence in situ hybridisation; Radiation sensitivity; Radiosensitivity; Radiotherapy; Radiotoxicity; Rheumatism; Rheumatoid arthritis

Chromosome aberrations in lymphocytes of patients undergoing radon spa therapy: An explorative mfish study - Paz, Nerea; Hartel, Carola; Nasonova, Elena; Donaubauer, Anna-Jasmina; Frey, Benjamin; Ritter, Sylvia (International Journal of Environmental Research and Public Health, 2021)
In the present exploratory study, we aim to elucidate the action of radon in vivo and to assess the possible health risks. Chromosome aberrations were analyzed in lymphocytes of two patients (P1, P2) undergoing radon spa therapy in Bad Steben (Germany). Both patients, suffering from painful chronic degenerative disorders of the spine and joints, received nine baths (1.2 kBq/L at 34 °C) over a 3-week period. Chromosome aberrations were analyzed before and 6, 12 and 30 weeks after the start of therapy using the high-resolution multiplex fluorescence in situ hybridization (mFISH) technique. For comparison, the lymphocytes from two healthy donors (HD1, HD2) were examined. P1 had a higher baseline aberration frequency than P2 and both healthy donors (5.3 ± 1.3 vs. 2.0 ± 0.8, 1.4 ± 0.3 and 1.1 ± 0.1 aberrations/100 analyzed metaphases, respectively). Complex aberrations, biomarkers of densely ionizing radiation, were found in P1, P2 and HD1. Neither the aberration frequency nor the fraction of complex aberrations increased after radon spa treatment, i.e., based on biological dosimetry, no increased health risk was found. It is worth noting that a detailed breakpoint analysis revealed potentially clonal aberrations in both patients. Altogether, our data show pronounced inter-individual differences with respect to the number and types of aberrations, complicating the risk analysis of low doses such as those received during radon therapy.
CRIS-Team Scopus Importer:2021-10-29
Keywords: Clonal aberrations; Complex aberrations; MFISH; Radon; T-cell receptor genes

Classification of primary cerebral lymphoma and glioblastoma featuring dynamic susceptibility contrast and apparent diffusion coefficient - Eisenhut, Felix; Schmidt, Manuel; Putz, Florian; Lettmaier, Sebastian; Fröhlich, Kilian; Arinrad, Soheil; Coras, Roland; Lücking, Hannes; Lang, Stefan; Fietkau, Rainer; Dörfler, Arnd (Brain Sciences, 2020)
This study aimed to differentiate primary central nervous system lymphoma (PCNSL) and glioblastoma (GBM) via multimodal MRI featuring radiomic analysis. MRI data sets of patients with histological proven PCNSL and GBM were analyzed retrospectively. Diffusion-weighted imaging (DWI) and dynamic susceptibility contrast (DSC) perfusion imaging were evaluated to differentiate contrast enhancing intracerebral lesions. Selective (contrast enhanced tumor area with the highest mean cerebral blood volume (CBV) value) and unselective (contouring whole contrast enhanced lesion) Apparent diffusion coefficient (ADC) measurement was performed. By multivariate logistic regression, a multiparametric model was compiled and tested for its diagnostic strength. A total of 74 patients were included in our study. Selective and unselective mean and maximum ADC values, mean and maximum CBV and ratioCBV as quotient of tumor CBV and CBV in contralateral healthy white matter were significantly larger in patients with GBM than PCNSL; minimum CBV was significantly lower in GBM than in PCNSL. The highest AUC for discrimination of PCNSL and GBM was obtained for selective mean and maximum ADC, mean and maximum CBV and ratioCBV. By integrating these five in a multiparametric model 100% of the patients were classified correctly. The combination of perfusion imaging (CBV) and tumor hot-spot selective ADC measurement yields reliable radiological discrimination of PCNSL from GBM with highest accuracy and is readily available in clinical routine.
CRIS-Team Scopus Importer:2020-12-04
Keywords: ADC; DSC; Glioblastoma; MRI; Multimodal; Primary central nervous system lymphoma

Classification of three prognostically different groups of head and neck cancer patients based on their metabolic response to induction chemotherapy (IC-1) - Semrau, Sabine; Schmidt, Daniela; Hecht, Markus; Haderlein, Marlen; Kitzsteiner, Christian; Müller, Susanna; Traxdorf, Maximilian; Agaimy, Abbas; Iro, Heinrich; Kuwert, Torsten; Fietkau, Rainer (Oral Oncology, 2020)
Objectives: There exist no uniform decision criteria for conservative organ preservation treatments in head and neck cancer patients. Even with 18F-FDG-PET/CT after induction chemotherapy patient selection is challenging. This study correlated metabolic tumor response with treatment types and recurrence patterns. Materials and methods: Decrease in SUVmax in 18F-FDG-PET/CT was measured 21–28 days after IC-1 in 102 patients and correlated to cancer-specific endpoints. Results: Residual SUVmax (resSUVmax) values were uniformly distributed across five cut-off levels (0–0.2 vs. >0.2–0.4 vs. >0.4–0.6 vs. >0.6–0.8 vs. >0.8) containing 20%, 25% 25%, 15% and 15% of patients. Patients were stratified into three response categories according to residual SUVmax (Group A: 0–0.4 = high response Group B: >0.4–0.8 = moderate response, Group C > 0.8 = non-response), 5-year local control rates were 90.5% (Group A) vs. 78.9% (Group B; univariate p = 0.07, multivariate: HR: 3.6, p = 0.03) vs. 49.4% (Group C vs. B; univariate p = 0.04, multivariate: HR 5.5, p < 0.01). After IC-1, Group A received chemoradiotherapy (CRT) only. Group B received surgery plus either (chemo)radiotherapy (B_S + RT/CRT) or chemoradiotherapy (B_CRT), yielding local control rates of 100% and 74.2% (p = 0.11). Group C received surgery plus CRT or CRT alone; both achieved equally poor local control (p = 0.71). Group C had significantly worse distant metastasis-free survival and overall survival than Groups A and B (p < 0.05). Conclusion: Metabolic response after IC-1 differentiates HNC patients into three subgroups predicting local tumor control. Non-response was associated with a poor outcome.
CRIS-Team Scopus Importer:2019-12-03
Keywords: 18F-FDG PET/CT; Chemoradiation; Chemoselection; Head and neck cancer; Hypopharynx; Induction chemotherapy; Larynx; Metabolic response; Resection

Clearance of primary necrotic cells by non-professional phagocytes - Schwegler, Manuela; Wirsing, Anna Maria; Dollinger, Alena J.; Abendroth, Benjamin; Putz, Florian; Fietkau, Rainer; Distel, Luitpold (Biology of the Cell, 2015)
Homotypic internalisation of tumour cells has frequently been observed in tumour tissue sections. Events of non-professional phagocytosis, however, may also occur in normal tissue if the number of dying cells exceeds the phagocytic capacity of professional phagocytes such as macrophages and dendritic cells. The aim of this study was to investigate the molecular background of non-professional phagocytosis of primary necrotic cells by neighbouring tumour cells and normal skin fibroblasts.We demonstrate that homotypic and heterotypic uptake of necrotic cells is a feature common to various cell types. Investigating critical stimuli of necrotic cell clearance we found that non-professional phagocytes require cytoskeleton rearrangement, recognition of phosphatidylserine and GTPase activity of dynamin II, which is normally engaged in endocytosis. Additionally, we have observed an accumulation of adhesion molecule E-cadherin, phosphorylated actin-linker protein ezrin, lysosomal-associated membrane protein 1 and microtubule-associated protein 1 light chain 3 at the site of engulfment. Loss of membrane integrity and an increase in the intracellular level of heat-shock protein 70 in the necrotic cells have also been observed.Our results shed light on the mechanism of necrotic cell removal by tumour cells and normal skin fibroblasts in vitro. It is reasonable to assume that this process has a physiological relevance in inflammation and autoimmune disease in normal tissue as well as in tumours regarding immune cell infiltration. We conclude that necrotic cell clearance by non-professional phagocytes contributes to the phagocytic activity by macrophages and that this process may prevent release of proinflammatory damage-associated molecular pattern molecules.
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Clinical application of breathing-adapted 4D CT: image quality comparison to conventional 4D CT - Werner, René; Szkitsak, Juliane; Madesta, Frederic; Büttgen, Laura; Wimmert, Lukas; Sentker, Thilo; Fietkau, Rainer; Haderlein, Marlen; Bert, Christoph; Gauer, Tobias; Hofmann, Christian (Strahlentherapie und Onkologie, 2023)
Purpose: 4D CT imaging is an integral part of 4D radiotherapy workflows. However, 4D CT data often contain motion artifacts that mitigate treatment planning. Recently, breathing-adapted 4D CT (i4DCT) was introduced into clinical practice, promising artifact reduction in in-silico and phantom studies. Here, we present an image quality comparison study, pooling clinical patient data from two centers: a new i4DCT and a conventional spiral 4D CT patient cohort. Methods: The i4DCT cohort comprises 129 and the conventional spiral 4D CT cohort 417 4D CT data sets of lung and liver tumor patients. All data were acquired for treatment planning. The study consists of three parts: illustration of image quality in selected patients of the two cohorts with similar breathing patterns; an image quality expert rater study; and automated analysis of the artifact frequency. Results: Image data of the patients with similar breathing patterns underline artifact reduction by i4DCT compared to conventional spiral 4D CT. Based on a subgroup of 50 patients with irregular breathing patterns, the rater study reveals a fraction of almost artifact-free scans of 89% for i4DCT and only 25% for conventional 4D CT; the quantitative analysis indicated a reduction of artifact frequency by 31% for i4DCT. Conclusion: The results demonstrate 4D CT image quality improvement for patients with irregular breathing patterns by breathing-adapted 4D CT in this first corresponding clinical data image quality comparison study.
CRIS-Team Scopus Importer:2023-04-14
Keywords: 4D CT; 4D radiotherapy; Image artifacts; Image quality

Clinical evaluation of semi-automatic landmark-based lesion tracking software for CT-scans - Dankerl, Peter; Dietzel, Matthias; Tsymbal, Alexey; Kramer, Martin; Seifert, Sascha; Uder, Michael; Hammon, Matthias; Cavallaro, Alexander Josef (Cancer Imaging, 2014)
To evaluate a semi-automatic landmark-based lesion tracking software enabling navigation between RECIST lesions in baseline and follow-up CT-scans.The software automatically detects 44 stable anatomical landmarks in each thoraco/abdominal/pelvic CT-scan, sets up a patient specific coordinate-system and cross-links the coordinate-systems of consecutive CT-scans. Accuracy of the software was evaluated on 96 RECIST lesions (target- and non-target lesions) in baseline and follow-up CT-scans of 32 oncologic patients (64 CT-scans). Patients had to present at least one thoracic, one abdominal and one pelvic RECIST lesion. Three radiologists determined the deviation between lesions' centre and the software's navigation result in consensus.The initial mean runtime of the system to synchronize baseline and follow-up examinations was 19.4 ± 1.2 seconds, with subsequent navigation to corresponding RECIST lesions facilitating in real-time. Mean vector length of the deviations between lesions' centre and the semi-automatic navigation result was 10.2 ± 5.1 mm without a substantial systematic error in any direction. Mean deviation in the cranio-caudal dimension was 5.4 ± 4.0 mm, in the lateral dimension 5.2 ± 3.9 mm and in the ventro-dorsal dimension 5.3 ± 4.0 mm.The investigated software accurately and reliably navigates between lesions in consecutive CT-scans in real-time, potentially accelerating and facilitating cancer staging.
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Clinical Evidence for Thermometric Parameters to Guide Hyperthermia Treatment - Ademaj, Adela; Veltsista, Danai P.; Ghadjar, Pirus; Marder, Dietmar; Oberacker, Eva; Ott, Oliver; Wust, Peter; Puric, Emsad; Hälg, Roger A.; Rogers, Susanne; Bodis, Stephan; Fietkau, Rainer; et al. (Cancers, 2022)
Hyperthermia (HT) is a cancer treatment modality which targets malignant tissues by heating to 40–43 °C. In addition to its direct antitumor effects, HT potently sensitizes the tumor to radiotherapy (RT) and chemotherapy (CT), thereby enabling complete eradication of some tumor entities as shown in randomized clinical trials. Despite the proven efficacy of HT in combination with classic cancer treatments, there are limited international standards for the delivery of HT in the clinical setting. Consequently, there is a large variability in reported data on thermometric parameters, including the temperature obtained from multiple reference points, heating duration, thermal dose, time interval, and sequence between HT and other treatment modalities. Evidence from some clinical trials indicates that thermal dose, which correlates with heating time and temperature achieved, could be used as a predictive marker for treatment efficacy in future studies. Similarly, other thermometric parameters when chosen optimally are associated with increased antitumor efficacy. This review summarizes the existing clinical evidence for the prognostic and predictive role of the most important thermometric parameters to guide the combined treatment of RT and CT with HT. In conclusion, we call for the standardization of thermometric parameters and stress the importance for their validation in future prospective clinical studies.
CRIS-Team Scopus Importer:2022-02-04
Keywords: Clinical evidence; Hyperthermia; Preclinical data; Thermometric parameters

Clinical experience with markerless tumor tracking - Bert, Christoph (RADIOTHERAPY AND ONCOLOGY, 2020)
CRIS-Team WoS Importer:2021-06-18

Clinical feasibility of a high-resolution thermal monitoring sheet for superficial hyperthermia in breast cancer patients - Bakker, Akke; Zweije, Remko; Kok, Henny Petra; Kolff, Merel Willemijn; Desiree van den Bongard, H. J.G.; Schmidt, Manfred; van Tienhoven, Geertjan; Crezee, Hans (Cancers, 2020)
Background: Accurate monitoring of skin surface temperatures is necessary to ensure treatment quality during superficial hyperthermia. A high-resolution thermal monitoring sheet (TMS) was developed to monitor the skin surface temperature distribution. The influence of the TMS on applicator performance was investigated, feasibility and ability to reliably monitor the temperature distribution were evaluated in a clinical study. Methods: Phantom experiments were performed to determine the influence of the TMS on power deposition patterns, applicator efficiency, and heat transfer of the water bolus for 434 and 915 MHz applicators. Clinical feasibility was evaluated in 10 women with locoregional recurrent breast cancer. Skin surface temperatures during consecutive treatments were monitored alternatingly with either standard Amsterdam UMC thermometry or TMS. Treatments were compared using (generalized) linear mixed models. Results: The TMS did not significantly affect power deposition patterns and applicator efficiency (1–2%), the reduced heat transfer of the water boluses (51–56%) could be compensated by adjusting the water bolus flow. Skin surface temperatures were monitored reliably, and no alteration of thermal toxicity was observed compared to standard Amsterdam UMC thermometry. Conclusion: Clinical application of the TMS is feasible. Power deposition patterns and applicator efficiency were not affected. Surface temperatures were monitored reliably.
CRIS-Team Scopus Importer:2020-12-18
Keywords: Hyperthermia; Quality assurance; Radiation oncology; Thermal monitoring

Clinical implementations of 4D pencil beam scanned particle therapy: Report on the 4D treatment planning workshop 2016 and 2017 - Trnkova, Petra; Knaeusl, Barbara; Actis, Oxana; Bert, Christoph; Biegun, Aleksandra K.; Boehlen, Till T.; Furtado, Hugo; Mcclelland, Jamie; Mori, Shinichiro; Rinaldi, Ilaria; Rucinski, Antoni; Knopf, Antje C. (Physica Medica, 2018)
In 2016 and 2017, the 8th and 9th 4D treatment planning workshop took place in Groningen (the Netherlands) and Vienna (Austria), respectively. This annual workshop brings together international experts to discuss research, advances in clinical implementation as well as problems and challenges in 4D treatment planning, mainly in spot scanned proton therapy. In the last two years several aspects like treatment planning, beam delivery, Monte Carlo simulations, motion modeling and monitoring, QA phantoms as well as 4D imaging were thoroughly discussed. This report provides an overview of discussed topics, recent findings and literature review from the last two years. Its main focus is to highlight translation of 4D research into clinical practice and to discuss remaining challenges and pitfalls that still need to be addressed and to be overcome.
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Clinically Relevant Radiation Exposure Differentially Impacts Forms of Cell Death in Human Cells of the Innate and Adaptive Immune System - Falcke, Sylvia; Rühle, Paul-Friedrich; Fietkau, Rainer; Frey, Benjamin; Gaipl, Udo; Deloch, Lisa (International Journal of Molecular Sciences, 2018)
In cancer treatments, especially high-dose radiotherapy (HDRT) is applied. Patients suffering from chronic inflammatory diseases benefit from low-dose radiation therapy (LDRT), but exposure to very low radiation doses can still steadily increase for diagnostic purposes. Yet, little is known about how radiation impacts on forms of cell death in human immune cells. In this study, the radiosensitivity of human immune cells of the peripheral blood was examined in a dose range from 0.01 to 60 Gy with regard to induction of apoptosis, primary necrosis, and secondary necrosis. Results showed that immune cells differed in their radiosensitivity, with monocytes being the most radioresistant. T cells mainly died by necrosis and were moderately radiosensitive. This was followed by B and natural killer (NK) cells, which died mainly by apoptosis. X-radiation had no impact on cell death in immune cells at very low doses (≤0.1 Gy). Radiation doses of LDRT (0.3⁻0.7 Gy) impacted on the more radiosensitive NK and B cells, which might contribute to attenuation of inflammation. Even single doses applied during RT of tumors did not erase the immune cells completely. These in vitro studies can be considered as the basis to optimize individual radiation therapy schemes in multimodal settings and to define suited time points for further inclusion of immunotherapies.
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Clinically significant CMV (re)activation during or after radiotherapy/chemotherapy of the brain : Correlation with neurological deterioration and improvement upon antiviral treatment - Goerig, Nicole; Semrau, S.; Frey, Benjamin; Korn, Klaus; Fleckenstein, Bernhard; Überla, Klaus; Dörfler, Arnd; Putz, Florian; Gaipl, Udo; Fietkau, Rainer (Strahlentherapie und Onkologie, 2016)
For both patients with high-grade gliomas and multiple cerebral metastases, radio(chemo)therapy is the standard therapy. Neurological decline during treatment is rarely attributed to infections of the brain but to tumor progression or side effects of radiotherapy.We present 4 cases of cytomegalovirus (CMV) viremia associated with neurological deterioration, which occurred during or shortly after radiotherapy and/or chemotherapy of the brain (brain metastases 2, high-grade glioma 1, carcinoma infiltrating brain 1). In all cases, neurological decline was sudden and unexpected, and causes such as increased intracranial pressure or tumor progression could be excluded radiologically. Treatment with dexamethasone and mannitol had no or only very short-term effects. General infections were either excluded or receding before the neurological symptoms occurred. All patients presented with decreasing levels of thrombocytes. In all cases, CMV (re)activation could be proven using blood test for CMV-DNA. The anti-CMV-IgG status suggested reactivation rather than a primary infection. One patient died within 72 h of onset of the symptoms (results of CMV tests were received postmortem). Diagnosis of 3 patients allowed successful administration of antiviral treatment, which greatly improved the general and neurological conditions of the patients within 48 h.Neurological deterioration during RT is hardly ever attributed to viral infections. These cases suggest that CMV reactivation and subsequent infection might actually be causative and has to be considered and treated.Further prospective studies verifying and investigating this observation in terms of frequency and clinical relevance seem indicated.
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Clinical outcome of concomitant vs interrupted BRAF inhibitor therapy during radiotherapy in melanoma patients - Hecht, Markus; Meier, Friedegund; Zimmer, Lisa; Polat, Bulent; Loquai, Carmen; Weishaupt, Carsten; Forschner, Andrea; Gutzmer, Ralf; Utikal, Jochen S.; Goldinger, Simone M.; Geier, Michael; Hassel, Jessica C.; et al. (British Journal of Cancer, 2018)
This corrects the article DOI: 10.1038/bjc.2017.85.
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Clinical radiation oncology trials in Germany: Time for clarification and professionalization - Fietkau, Rainer; Wenz, Frederik (Strahlentherapie und Onkologie, 2015)
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Clonogenicity-based radioresistance determines the expression of immune suppressive immune checkpoint molecules after hypofractionated irradiation of MDA-MB-231 triple-negative breast cancer cells - Gehre, Simon; Meyer, Felix; Sengedorj, Azzaya; Grottker, Fridolin; Reichardt, Clara; Alomo, Jannik; Borgmann, Kerstin; Frey, Benjamin; Fietkau, Rainer; Rückert, Michael; Gaipl, Udo (Frontiers in Oncology, 2023)
Only a subset of patients with triple-negative breast cancer (TNBC) benefits from a combination of radio- (RT) and immunotherapy. Therefore, we aimed to examine the impact of radioresistance and brain metastasizing potential on the immunological phenotype of TNBC cells following hypofractionated RT by analyzing cell death, immune checkpoint molecule (ICM) expression and activation of human monocyte-derived dendritic cells (DCs). MDA-MB-231 triple-negative breast cancer tumor cells were used as model system. Apoptosis was the dominant cell death form of brain metastasizing tumor cells, while Hsp70 release was generally significantly increased following RT and went along with necrosis induction. The ICMs PD-L1, PD-L2, HVEM, ICOS-L, CD137-L and OX40-L were found on the tumor cell surfaces and were significantly upregulated by RT with 5 x 5.2 Gy. Strikingly, the expression of immune suppressive ICMs was significantly higher on radioresistant clones compared to their respective non-radioresistant ones. Although hypofractionated RT led to significant cell death induction and release of Hsp70 in all tumor cell lines, human monocyte-derived DCs were not activated after co-incubation with RT-treated tumor cells. We conclude that radioresistance is a potent driver of immune suppressive ICM expression on the surface of TNBC MDA-MB-231 cells. This mechanism is generally known to predominantly influence the effector phase, rather than the priming phase, of anti-tumor immune responses.
CRIS-Team Scopus Importer:2023-05-19
Keywords: breast cancer; dendritic cells; immune checkpoint molecules; radioresistance; radiotherapy; tumor cell death

Co-expression gene modules involved in cisplatin-induced peripheral neuropathy according to sensitivity, status, and severity - Zhou, Rui Hao; Chen, Chan; Jin, Su Han; Li, Jun; Xu, Zi Hao; Ye, Ling; Zhou, Jianguo (Journal of the Peripheral Nervous System, 2020)
Chemotherapy-induced peripheral neuropathy (CIPN) is among the most disabling and frustrating problems for cancer survivors. The neurotoxicity caused by cisplatin varies greatly among patients, and few predictors of appearance, duration of symptoms, susceptibility, or severity are available. A deeper understanding of the mechanisms underlying individual differences in status, severity, or sensitivity in response to cisplatin treatment is therefore required. By analyzing the GSE64174 gene expression profile and constructing a weighted gene co-expression network analysis (WGCNA) network, we screened gene modules and hub genes related to CIPN status, severity and sensitivity. We first identified the transcriptome profile of mouse dorsal root ganglion (DRG) samples and transformed their genes to human DRG counterparts. We then constructed WGCNA gene modules via optimal soft-threshold power-identification and module-preservation analysis. Comprehensive analysis and identification of module hub genes were performed via functional-enrichment analysis and significant common hub genes were identified, including “Cytoscape_cytoHubba,” “Cytoscape_MCODE,” and “Metascape_MCODE.” Brown, green, and blue modules were selected to represent CIPN sensitivity, status, and severity, respectively, via trait-module correlational analysis. Additionally, functional enrichment analysis results indicated that these three modules were associated with some crucial biological functions, such as neutrophil migration, chemokine-mediated signaling pathway, and PI3K-Akt signaling pathway. We then identified seven common hub genes via three methods, including CXCL10, CCL21, CCR2, CXCR4, TLR4, NPY1R, and GALR2, related to CIPN status, severity and sensitivity. Our results provide possible targets and mechanism insights into the development and progress of CIPN, which can guide further transformation and pre-clinical research.
CRIS-Team Scopus Importer:2020-09-11
Keywords: chemotherapy-induced peripheral neuropathy; cisplatin; hub gene; neuropathic pain; weighted gene co-expression network analysis

Combination of an ultrafast TWIST-VIBE Dixon sequence protocol and diffusion-weighted imaging into an accurate easily applicable classification tool for masses in breast MRI - Peter, Sandra C.; Wenkel, Evelyn; Weiland, Elisabeth; Dietzel, Matthias; Janka, Rolf Matthias; Hartmann, Arndt; Emons, Julius; Uder, Michael; Ellmann, Stephan (European Radiology, 2020)
Objectives: This study aimed to develop a tool for the classification of masses in breast MRI, based on ultrafast TWIST-VIBE Dixon (TVD) dynamic sequences combined with DWI. TVD sequences allow to abbreviate breast MRI protocols, but provide kinetic information only on the contrast wash-in, and because of the lack of the wash-out kinetics, their diagnostic value might be hampered. A special focus of this study was thus to maintain high diagnostic accuracy in lesion classification. Materials and methods: Sixty-one patients who received breast MRI between 02/2014 and 04/2015 were included, with 83 reported lesions (60 malignant). Our institute’s standard breast MRI protocol was complemented by an ultrafast TVD sequence. ADC and peak enhancement of the TVD sequences were integrated into a generalised linear model (GLM) for malignancy prediction. For comparison, a second GLM was calculated using ADC and conventional DCE curve type. The resulting GLMs were evaluated for standard diagnostic parameters. For easy application of the GLMs, nomograms were created. Results: The GLM based on peak enhancement of the TVD and ADC was as equally accurate as the GLM based on conventional DCE and ADC, with no significant differences (sensitivity, 93.3%/93.3%; specificity, 91.3%/87.0%; PPV, 96.6%/94.9%; NPV, 84.0%/83.3%; all, p ≥ 0.315). Conclusions: This study presents a method to integrate ultrafast TVD sequences into a breast MRI protocol, allowing a reduction of the examination time while maintaining diagnostic accuracy. A GLM based on the combination of TVD-derived peak enhancement and ADC provides high diagnostic accuracy, and can be easily applied using a nomogram. Key Points: • Ultrafast TWIST-VIBE Dixon sequence protocols in combination with diffusion-weighted imaging allow to shorten breast MRI examinations, while diagnostic accuracy is maintained. • Integrating peak enhancement from the TWIST-VIBE Dixon sequence and the apparent diffusion coefficient into a generalised linear model provides a comprehensible image evaluation approach. • This approach is further facilitated by nomograms.
CRIS-Team Scopus Importer:2020-02-11
Keywords: Breast cancer; Diagnostic imaging; Diffusion magnetic resonance imaging; Magnetic resonance imaging; Statistical model

Combination of gas plasma and radiotherapy has immunostimulatory potential and additive toxicity in murine melanoma cells in vitro - Pasqual-Melo, Gabriella; Sagwal, Sanjeev Kumar; Freund, Eric; Gandhirajan, Rajesh Kumar; Frey, Benjamin; von Woedtke, Thomas; Gaipl, Udo; Bekeschus, Sander (International Journal of Molecular Sciences, 2020)
Despite continuous advances in therapy, malignant melanoma is still among the deadliest types of cancer. At the same time, owing to its high plasticity and immunogenicity, melanoma is regarded as a model tumor entity when testing new treatment approaches. Cold physical plasma is a novel anticancer tool that utilizes a plethora of reactive oxygen species (ROS) being deposited on the target cells and tissues. To test whether plasma treatment would enhance the toxicity of an established antitumor therapy, ionizing radiation, we combined both physical treatment modalities targeting B16F10 murine melanoma cell in vitro. Repeated rather than single radiotherapy, in combination with gas plasma-introduced ROS, induced apoptosis and cell cycle arrest in an additive fashion. In tendency, gas plasma treatment sensitized the cells to subsequent radiotherapy rather than the other way around. This was concomitant with increased levels of TNFα, IL6, and GM-CSF in supernatants. Murine JAWS dendritic cells cultured in these supernatants showed an increased expression of cell surface activation markers, such as MHCII and CD83. For PD-L1 and PD-L2, increased expression was observed. Our results are the first to suggest an additive therapeutic effect of gas plasma and radiotherapy, and translational tumor models are needed to develop this concept further.
CRIS-Team Scopus Importer:2020-02-28
Keywords: KINPen; Oncology; Plasma medicine; Reactive oxygen species; ROS

Combination of growth pattern and tumor regression identifies a high-risk group in neoadjuvant treated rectal cancer patients - Jeßberger, Jonas; Erlenbach-Wuensch, Katharina; Posselt, Rebecca; Haderlein, Marlen; Agaimy, Abbas; Fietkau, Rainer; Hartmann, Arndt; Distel, Luitpold (Journal of Digestive Diseases, 2017)
To analyze the prognostic effect of E-cadherin expression, the growth pattern of the tumor and the regression grade in a rectal cancer cohort treated with neoadjuvant radiochemotherapy (RCT).A total of 223 patients with rectal cancer treated with neoadjuvant RCT followed by surgery were included. Altogether 88 biopsies prior to RCT and 213 tumor resections in an average of 55 days post-RCT were investigated. Protein expression of E-cadherin and tumor growth pattern (solid glandular vs single-cell pattern) was assessed by staining tissue microarrays. The regression grade at the invasion front was determined according to the Dworak scale.There was a significant decrease of E-cadherin expression (P = 0.002) and a significant increased single-cell growth (P < 0.001) at the invasion front in tumor samples after RCT compared with primary biopsies of the tumor. A low E-cadherin expression in the biopsy was related to a longer metastasis-free survival (P = 0.033) and tumor-specific survival (P = 0.030). Post-RCT single-cell growth at the tumor invasion front was a prognostic factor for longer tumor-specific survival (P = 0.021). A combination of growth pattern and the Dworak regression grade was an independent prognostic parameter for tumor-specific survival (P = 0.015).Loss of E-cadherin protein expression in the pretreatment biopsy of rectal cancer is associated with fewer metastases and improved survival. Furthermore, the growth pattern in the post-RCT resection specimen has a prognostic value for survival. A combination of growth pattern and tumor regression score (the RegPat score) showed the highest discriminatory power to identify high-risk patients.
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Combination of ionising radiation with hyperthermia increases the immunogenic potential of B16-F10 melanoma cells in vitro and in vivo - Werthmöller, Nina; Frey, Benjamin; Rueckert, Michael; Lotter, Michael; Fietkau, Rainer; Gaipl, Udo (International Journal of Hyperthermia, 2016)
Mild hyperthermia (HT) (41.5 °C for 30-60 min) has been shown in various cell culture systems, preclinical and clinical models to be a very potent radiosensitiser. Recent research suggests that local HT application in combination with standard tumour therapies such as radiotherapy (RT) and/or chemotherapy may not only improve local tumour control but also lead to systemic and immune mediated anti-tumour responses. Melanoma has been proven to be rather radioresistant and mostly only the addition of immunotherapy is capable of inducing beneficial anti-melanoma responses. This work therefore focuses on whether HT increases the immunogenic potential of B16-F10 mouse melanoma cells in combination with RT. The in vitro experiments revealed that combination of RT with HT resulted in an increased percentage of apoptotic and necrotic melanoma cells and an increased release of the danger signal heat shock protein 70 (Hsp70) and high mobility group box protein 1 (HMGB1). HT alone was also capable of inducing this release. We set up local irradiation and heating procedures of B16-F10 tumour-bearing C57/BL6 mice and revealed that the tumour growth of tumours treated with RT plus HT was significantly retarded compared to tumours treated only with RT. This combined treatment generated a beneficial tumour microenvironment by enhancing the infiltration of CD11c + /MHCII + /CD86+ dendritic cells, CD8+ T cells, and NK cells, and decreasing that of regulatory T cells and myeloid-derived suppressor cells. We conclude that HT in combination with RT has an immune-stimulating potential that might result in anti-tumour immunity.
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Combination of Markerless Surrogates for Motion Estimation in Radiation Therapy - Geimer, Tobias; Unberath, Mathias; Taubmann, Oliver; Bert, Christoph; Maier, Andreas (Computer Assisted Radiology and Surgery (CARS) 2016: Proceedings of the 30th International Congress and Exhibition, 2016)
UnivIS-Import:2017-12-18:Pub.2016.tech.IMMD.IMMD5.combin_2
Keywords: Motion Modeling; X-ray; Range Imaging; Dimensionality Reduction; Regression

Combinations of radiotherapy with vaccination and immune checkpoint inhibition differently affect primary and abscopal tumor growth and the tumor microenvironment - Rückert, Michael; Deloch, Lisa; Frey, Benjamin; Schlücker, Eberhard; Fietkau, Rainer; Gaipl, Udo (Cancers, 2021)
Radiotherapy (RT) is known to have immune‐modulatory properties. We hypothesized that RT and inactivated whole tumor cell vaccines generated with high hydrostatic pressure (HHP) synergize to retard the tumor growth which can be additionally improved with anti‐PD‐1 treatment. In abscopal tumor models, we injected mice with B16‐F10 melanoma or TS/A mammary tumors. To evaluate the efficiency of RT in combination with HHP vaccines, we locally irradiated only one tumor with 2 × 8 Gy or 3 × 8 Gy. HHP vaccines further retarded the growth of locally irradiated (2 × 8 Gy) tumors. However, HHP vaccination combined with RT failed to induce abscopal anti‐tumor immune responses, namely those to non‐irradiated tumors, and even partly abrogated those which were induced with RT plus anti‐PD‐1. In the latter group, the abscopal effects were accompanied by an elevated infiltration of CD8+ T cells, monocytes/macrophages, and dendritic cells. 3 × 8 Gy failed to induce abscopal effects in association with increased expression of immunosuppressive checkpoint molecules compared to 2 × 8 Gy. We conclude that HHP vaccines induce anti‐tumor effects, but only if the tumor microenvironment was previously modulated by hypofractionated RT with not too many fractions, but failed to improve RT plus anti‐PD‐induced abscopal responses that are characterized by distinct immune alterations.
CRIS-Team Scopus Importer:2021-03-05
Keywords: Abscopal effect; High hydrostatic pressure; Immune checkpoint inhibition; Radiotherapy; Tumor microenvironment; Tumor‐infiltrating immune cells; Vaccination

Commercially Available Gene Expression Assays as Predictive Tools for Adjuvant Radiotherapy? A Critical Review - Krug, David; Baumann, René; Budach, Wilfried; Duma, Marciana Nona; Dunst, Jürgen; Feyer, Petra; Fietkau, Rainer; Haase, Wulf; Harms, Wolfgang; Hehr, Thomas; Piroth, Marc D.; Sedlmayer, Felix; et al. (Breast Care, 2020)
Background: Gene expression assays are increasingly used for decision-making regarding adjuvant chemotherapy in patients with hormone receptor-positive, HER2-negative breast cancer. There are some clinical situations in which there is also a need for better prognostic and predictive markers to better estimate the amount of benefit from adjuvant radiotherapy. The rising availability of gene expression analyses prompts the question whether their results can also be used to guide clinical decisions regarding adjuvant radiation. Summary: Multiple studies suggest a correlation between results from gene expression assays and locoregional recurrence rates. Only few publications addressed the predictive value of results from gene expression analysis for the role of adjuvant radiotherapy in different settings. Key Messages: To date, the available evidence on the possible predictive value of gene expression assays for radiotherapy does not support their inclusion into the decision-making process for adjuvant radiation. This is due to methodological weaknesses and limitations regarding patient selection, the nonrandomized design of all studies in terms of radiotherapy use, and limited availability of tissue from prospective trials. Thus, utilization of the present knowledge for clinical indication of radiotherapy should be very cautious.
CRIS-Team Scopus Importer:2020-02-14
Keywords: Breast cancer; Gene expression assay; Oncotype DX; Predictive marker; Radiotherapy

Commissioning of an integrated platform for time-resolved treatment delivery in scanned ion beam therapy by means of optical motion monitoring - Fattori, Giovanni; Saito, N.; Seregni, M.; Kaderka, R.; Pella, A.; Constantinescu, A.; Riboldi, Marco; Steidl, P.; Cerveri, P.; Bert, Christoph; Durante, Marco; Baroni, G. (Technology in Cancer Research & Treatment, 2014)
The integrated use of optical technologies for patient monitoring is addressed in the framework of time-resolved treatment delivery for scanned ion beam therapy. A software application has been designed to provide the therapy control system (TCS) with a continuous geometrical feedback by processing the external surrogates tridimensional data, detected in real-time via optical tracking. Conventional procedures for phase-based respiratory phase detection were implemented, as well as the interface to patient specific correlation models, in order to estimate internal tumor motion from surface markers. In this paper, particular attention is dedicated to the quantification of time delays resulting from system integration and its compensation by means of polynomial interpolation in the time domain. Dedicated tests to assess the separate delay contributions due to optical signal processing, digital data transfer to the TCS and passive beam energy modulation actuation have been performed. We report the system technological commissioning activities reporting dose distribution errors in a phantom study, where the treatment of a lung lesion was simulated, with both lateral and range beam position compensation. The zero-delay systems integration with a specific active scanning delivery machine was achieved by tuning the amount of time prediction applied to lateral (14.61 ± 0.98 ms) and depth (34.1 ± 6.29 ms) beam position correction signals, featuring sub-millimeter accuracy in forward estimation. Direct optical target observation and motion phase (MPh) based tumor motion discretization strategies were tested, resulting in 20.3(2.3)% and 21.2(9.3)% median (IQR) percentual relative dose difference with respect to static irradiation, respectively. Results confirm the technical feasibility of the implemented strategy towards 4D treatment delivery, with negligible percentual dose deviations with respect to static irradiation.
EVALuna2:18207

Common RUNX3 missense variant contributes to psoriatic arthritis by modifying differentiation of CD8(+) T-cells - Kerker, Iris; Löhr, Sabine; Uebe, Steffen; Popp, Bernt; Vasileiou, Georgia; Bowes, John; Kirchner, Philipp; Becker, Ina; Giardina, Emiliano; Korendowych, Eleanor; Ekici, Arif Bülent; Ho, Pauline; et al. (EUROPEAN JOURNAL OF HUMAN GENETICS, 2022)
CRIS-Team WoS Importer:2022-05-06

Comparative study and simulation of tumor cell inactivation by microwave and conventional heating - Rosin, Andreas; Hader, Michael; Drescher, Corinna; Suntinger, Magdalena; Gerdes, Thorsten; Willert-Porada, Monika; Gaipl, Udo; Frey, Benjamin (Compel-The International Journal For Computation and Mathematics in Electrical and Electronic Engineering, 2018)
Purpose This paper aims to investigate in a self-designed closed loop reactor process conditions for thermal inactivation of B16 melanoma cells by microwave and conventional heating. Design/methodology/approach Besides control experiments (37 degrees C), inactivation rate was determined in the range from 42 degrees C to 46 degrees C. Heating was achieved either by microwave radiation at 2.45 GHz or by warm water. To distinguish viable from dead cells, AnnexinV staining method was used and supported by field effect scanning electron microscopy (FE-SEM) imaging. Furthermore, numerical simulations were done to get a closer look into both heating devices. To investigate the thermal influence on cell inactivation and the differences between heating methods, a reaction kinetics approach was added as well. Findings Control experiments and heating at 42 degrees C resulted in low inactivation rates. Inactivation rate at 44 degrees C remained below 12% under conventional, whereas it increased to >70% under microwave heating. At 46 degrees C, inactivation rate attained 68% under conventional heating; meanwhile, even 88% were determined under microwave heating. FE-SEM images showed a porous membrane structure under microwave heating in contrast to mostly intact conventional heated cells. Numerical simulations of both heating devices and a macroscopic Arrhenius approach could not sufficiently explain the observed differences in inactivation. Originality/value A combination of thermal and electrical effects owing to microwave heating results in higher inactivation rates than conventional heating achieves. Nevertheless, it was not possible to determine the exact mechanisms of inactivation under microwave radiation.
EVALuna2:36524

Comparing local and systemic control between partial-and whole-breast radiotherapy in low-risk breast cancer—a meta-analysis of randomized trials - Haussmann, Jan; Budach, Wilfried; Strnad, Vratislav; Corradini, Stefanie; Krug, David; Schmidt, Livia; Tamaskovics, Balint; Bölke, Edwin; Simiantonakis, Ioannis; Kammers, Kai; Matuschek, Christiane (Cancers, 2021)
Purpose/Objective: The standard treatment for localized low-risk breast cancer is breast-conserving surgery, followed by adjuvant radiotherapy and appropriate systemic therapy. As the majority of local recurrences occur at the site of the primary tumor, numerous trials have investigated partial-breast irradiation (PBI) instead of whole-breast treatment (WBI) using a multitude of irradiation techniques and fractionation regimens. This meta-analysis addresses the impact on disease-specific endpoints, such as local and regional control, as well as disease-free survival of PBI compared to that of WBI in published randomized trials. Material and Methods: We conducted a systematic literature review and searched for randomized trials comparing WBI and PBI in early-stage breast cancer with publication dates after 2009. The meta-analysis was based on the published event rates and the effect sizes for available oncological endpoints of at least two trials reporting on them. We evaluated in-breast tumor recurrences (IBTR), local recurrences at the primary site and elsewhere in the ipsilateral breast, regional recurrences (RR), distant metastasis-free interval (DMFI), disease-free survival (DFS), contralateral breast cancer (CBC), and second primary cancer (SPC). Furthermore, we aimed to assess the impact of different PBI techniques and subgroups on IBTR. We performed all statistical analyses using the inverse variance heterogeneity model to pool effect sizes. Results: For the intended meta-analysis, we identified 13 trials (overall 15,561 patients) randomizing between PBI and WBI. IBTR was significantly higher after PBI (OR = 1.66; CI-95%: 1.07–2.58; p = 0.024) with an absolute difference of 1.35%. We detected significant heterogeneity in the analysis of the PBI technique with intraoperative radiotherapy resulting in higher local relapse rates (OR = 3.67; CI-95%: 2.28–5.90; p < 0.001). Other PBI techniques did not show differences to WBI in IBTR. Both strategies were equally effective at the primary tumor site, but PBI resulted in statistically more IBTRs elsewhere in the ipsilateral breast. IBTRs after WBI were more likely to be located at the primary tumor bed, whereas they appeared equally distributed within the breast after PBI. RR was also more frequent after PBI (OR = 1.75; CI-95%: 1.07–2.88; p < 0.001), yet we did not detect any differences in DMFI (OR = 1.08; CI-95%:0.89–1.30; p = 0.475). DFS was significantly longer in patients treated with WBI (OR = 1.14; CI-95%: 1.02–1.27; p = 0.003). CBC and SPC were not different in the test groups (OR = 0.81; CI-95%: 0.65–1.01; p = 0.067 and OR = 1.09; CI-95%: 0.85–1.40; p = 0.481, respectively). Conclusion: Limiting the target volume to partial-breast radiotherapy appears to be appropriate when selecting patients with a low risk for local and regional recurrences and using a suitable technique.
CRIS-Team Scopus Importer:2021-06-18
Keywords: Breast cancer; Local recurrence; Partial-breast treatment; Radiotherapy

Comparison of different CDK4/6 Kinase Inhibitors (Palbociclib, Ribociclib, Abemaciclib) and their Influence on the Effectiveness of simultaneous Radiation Therapy - Jost, Tina; Hecht, Markus; Fietkau, Rainer; Distel, Luitpold (STRAHLENTHERAPIE UND ONKOLOGIE, 2020)
CRIS-Team WoS Importer:2020-10-02

Comparison of intelligent 4D CT sequence scanning and conventional spiral 4D CT: A first comprehensive phantom study - Werner, René; Szkitsak, Juliane; Sentker, Thilo; Madesta, Frederic; Schwarz, Annette; Fernolendt, Susanne; Vornehm, Marc; Gauer, Tobias; Bert, Christoph; Hofmann, Christian (Physics in Medicine and Biology, 2021)
4D CT imaging is a cornerstone of 4D radiotherapy treatment. Clinical 4D CT data are, however, often affected by severe artifacts. The artifacts are mainly caused by breathing irregularity and retrospective correlation of breathing phase information and acquired projection data, which leads to insufficient projection data coverage to allow for proper reconstruction of 4D CT phase images. The recently introduced 4D CT approach i4DCT (intelligent 4D CT sequence scanning) aims to overcome this problem by breathing signal-driven tube control. The present motion phantom study describes the first in-depth evaluation of i4DCT in a real-world scenario. Twenty-eight 4D CT breathing curves of lung and liver tumor patients with pronounced breathing irregularity were selected to program the motion phantom. For every motion pattern, 4D CT imaging was performed with i4DCT and a conventional spiral 4D CT mode. For qualitative evaluation, the reconstructed 4D CT images were presented to clinical experts, who scored image quality. Further quantitative evaluation was based on established image intensity-based artifact metrics to measure (dis)similarity of neighboring image slices. In addition, beam-on and scan times of the scan modes were analyzed. The expert rating revealed a significantly higher image quality for the i4DCT data. The quantitative evaluation further supported the qualitative: While 20% of the slices of the conventional spiral 4D CT images were found to be artifact-affected, the corresponding fraction was only 4% for i4DCT. The beam-on time (surrogate of imaging dose) did not significantly differ between i4DCT and spiral 4D CT. Overall i4DCT scan times (time between first beam-on and last beam-on event, including scan breaks to compensate for breathing irregularity) were, on average, 53% longer compared to spiral CT. Thus, the results underline that i4DCT significantly improves 4D CT image quality compared to standard spiral CT scanning in the case of breathing irregularity during scanning.
CRIS-Team Scopus Importer:2021-02-12
Keywords: 4D CT; I4DCT; Motion artifacts; Radiotherapy

Comparison of Intrinsic PAM50 Gene Expression Analysis and Immunohistochemical Subtypes of Salivary Duct Carcinoma - Erber, Ramona; Stoehr, Robert; Haller, Florian; Haderlein, Marlen; Hartmann, Arndt; Agaimy, Abbas (LABORATORY INVESTIGATION, 2020)
CRIS-Team WoS Importer:2020-03-24

Comparison of MRI coils and RT-positioning systems for optimal MRI scanning in SRS cases - Mengling, Veit; Perrin, R.; Putz, Florian; Fietkau, Rainer; Bert, Christoph (RADIOTHERAPY AND ONCOLOGY, 2020)
CRIS-Team WoS Importer:2021-06-18

Comparison of performance between rigid and non-rigid software registering CT to FDG-PET - Wolz, Gabriele; Nömayr, Anton; Hothorn, Torsten; Hornegger, Joachim; Römer, Wolfgang; Bautz, Werner; Kuwert, Torsten (International Journal of Computer Assisted Radiology and Surgery, 2007)
Object: This retrospective study compares the anatomical accuracy of automated rigid and non-rigid registration software for aligning data from separately performed X-ray computed tomography (CT) and positron emission tomography with F-18-deoxyglucose (PET). Materials and methods: Analyses were performed on independently acquired PET and CT data from 40 tumor patients. Rigid as well as non-rigid automated fusion was carried out using the commercially available Mirada 7D platform (MIR and MINR, respectively) as well as a second automated non-rigid registration based on a variational image registration approach (VIR). Distances between lesion representation on PET and CT of 105 malignant lesions were measured in X-, Y-, and Z-directions. Statistical evaluation was performed using mixed effect analysis, comparing separately MIR with MINR and VIR with MINR. Results: The percentage of lesions misregistered by less than 15 mm varied from 70% for MIR and MINR in Z-direction to 93% for VIR in X-direction. The average X-, Y- and Z-distances ranged between 5.9 ± 5.7 mm for VIR in X-direction and 12.8 ± 9.7 mm for MIR in Z-direction. MINR was significantly more accurate than MIR in Y-direction. Furthermore, VIR aligned thoracic lesions in the X- direction significantly better than MINR. Conclusion: The accuracy of rigid and non-rigid automated image registration can be expected to be better than 15 mm for the majority of lesions. Alignment tended to be more accurate with non-rigid registration. © CARS 2007.

Complete Remission with consecutive Pneumonitis in metastatic Bronchogenic Carcinoma after combination of Radiotherapy and Nivolumab - Immunological Correlate in peripheral Blood - Hecht, Markus; Donaubauer, Anna-Jasmina; Becker, I.; Rutzner, Sandra; Lubgan, Dorota; Lettmaier, S.; Haderlein, Marlen; Wolf, W.; Fietkau, Rainer; Gaipl, Udo; Frey, Benjamin (STRAHLENTHERAPIE UND ONKOLOGIE, 2019)
CRIS-Team WoS Importer:2019-06-07

Cone-beam CT imaging with laterally enlarged field of view based on independently movable source and detector - Karius, Andre; Szkitsak, Juliane; Strnad, Vratislav; Fietkau, Rainer; Bert, Christoph (Medical Physics, 2023)
Background: CBCT imaging with field of views (FOVs) exceeding the size of scans acquired in the conventional imaging geometry, i.e. with opposing source and detector, is of high clinical importance for many medical fields. A novel approach for enlarged FOV scanning with one full-scan (EnFOV360) or two short-scans (EnFOV180) using an O-arm system arises from non-isocentric imaging based on independent source and detector rotations. Purpose: The presentation, description, and experimental validation of this novel approach and the novel scanning techniques EnFOV360 and EnFOV180 for an O-arm system forms the scope of this work. Methods: We describe the EnFOV360, EnFOV180, and non-isocentric imaging techniques for the acquisition of laterally extended FOVs. For their experimental validation, scans of dedicated quality assurance as well as anthropomorphic phantoms were acquired, with the phantoms being placed both within the tomographic plane and at the longitudinal FOV border with and without lateral shifts from the gantry center. Based on this, geometric accuracy, contrast-noise-ratio (CNR) of different materials, spatial resolution, noise characteristics, as well as CT number profiles were quantitatively assessed. Results were compared to scans performed with the conventional imaging geometry. Results: With EnFOV360 and EnFOV180, we increased the in-plane size of acquired FOVs from 250 × 250 mm2 obtained for the conventional imaging geometry to up to 400 × 400 mm2 for the performed measurements. Geometric accuracy was very high for all scanning techniques with mean values ≤0.21 ± 0.11 mm. CNR and spatial resolution were comparable between isocentric and non-isocentric full-scans as well as EnFOV360, whereas substantial image quality deteriorations in this respect were observed for EnFOV180. Image noise in the isocenter was lowest for conventional full-scans with 13.4 ± 0.2 HU. For laterally shifted phantom positions, noise increased for conventional scans and EnFOV360, whereas noise reductions were observed for EnFOV180. Considering the anthropomorphic phantom scans, both EnFOV360 and EnFOV180 were comparable to conventional full-scans. Conclusion: Both enlarged FOV techniques have high potential for imaging laterally extended FOVs. EnFOV360 revealed an image quality comparable to conventional full-scans in general. EnFOV180 showed an inferior performance particularly regarding CNR and spatial resolution.
CRIS-Team Scopus Importer:2023-05-26
Keywords: cone-beam computed tomography; extended field of view; independent gantry rotations

Consensus guidelines for the definition, detection and interpretation of immunogenic cell death - Galluzzi, Lorenzo; Vitale, Ilio; Warren, Sarah; Adjemian, Sandy; Agostinis, Patrizia; Martinez, Aitziber Buqué; Chan, Timothy A.; Coukos, George; Demaria, Sandra; Deutsch, Eric; Draganov, Dobrin; Edelson, Richard L.; et al. (Journal for ImmunoTherapy of Cancer, 2020)
Cells succumbing to stress via regulated cell death (RCD) can initiate an adaptive immune response associated with immunological memory, provided they display sufficient antigenicity and adjuvanticity. Moreover, multiple intracellular and microenvironmental features determine the propensity of RCD to drive adaptive immunity. Here, we provide an updated operational definition of immunogenic cell death (ICD), discuss the key factors that dictate the ability of dying cells to drive an adaptive immune response, summarize experimental assays that are currently available for the assessment of ICD in vitro and in vivo, and formulate guidelines for their interpretation.
CRIS-Team Scopus Importer:2020-03-27
Keywords: immunology; molecular biology; oncology

Consensus in determining the resectability of locally progressed pancreatic ductal adenocarcinoma - results of the Conko-007 multicenter trial - Wittel, U. A.; Lubgan, Dorota; Ghadimi, M.; Belyaev, O.; Uhl, W.; Bechstein, W. O.; Grützmann, Robert; Hohenberger, Werner; Schmid, Andrea; Jacobasch, L.; Croner, R. S.; Reinacher-Schick, A.; et al. (BMC Cancer, 2019)
BACKGROUND: One critical step in the therapy of patients with localized pancreatic cancer is the determination of local resectability. The decision between primary surgery versus upfront local or systemic cancer therapy seems especially to differ between pancreatic cancer centers. In our cohort study, we analyzed the independent judgement of resectability of five experienced high volume pancreatic surgeons in 200 consecutive patients with borderline resectable or locally advanced pancreatic cancer. METHODS: Pretherapeutic CT or MRI scans of 200 consecutive patients with borderline resectable or locally advanced pancreatic cancer were evaluated by 5 independent pancreatic surgeons. Resectability and the degree of abutment of the tumor to the venous and arterial structures adjacent to the pancreas were reported. Interrater reliability and dispersion indices were compared. RESULTS: One hundred ninety-four CT scans and 6 MRI scans were evaluated and all parameters were evaluated by all surgeons in 133 (66.5%) cases. Low agreement was observed for tumor infiltration of venous structures (κ = 0.265 and κ = 0.285) while good agreement was achieved for the abutment of the tumor to arterial structures (interrater reliability celiac trunk κ = 0.708 P < 0.001). In patients with vascular tumor contact indicating locally advanced disease, surgeons highly agreed on unresectability, but in patients with vascular tumor abutment consistent with borderline resectable disease, the judgement of resectability was less uniform (dispersion index locally advanced vs. borderline resectable p < 0.05). CONCLUSION: Excellent agreement between surgeons exists in determining the presence of arterial abutment and locally advanced pancreatic cancer. The determination of resectability in borderline resectable patients is influenced by additional subjective factors. TRIAL REGISTRATION: EudraCT:2009-014476-21 (2013-02-22) and NCT01827553 (2013-04-09).
CRIS-Team Scopus Importer:2019-10-29
Keywords: Borderline resectable; Determination of resectability; Locally advanced; Pancreatic cancer; Prospective randomized multicenter trial

Contrast medium application in pediatric high-pitch cardiovascular CT angiography: manual or power injection? - Saake, Marc; Lell, Michael; Rompel, Oliver; Glöckler, Martin; May, Matthias; Eller, Achim; Achenbach, Stephan; Uder, Michael; Wüst, Wolfgang (Journal of Cardiovascular Computed Tomography, 2014)
Dual-source CT offers accurate depiction of cardiac structures in children with congenital heart disease. For cardiac CT, optimal enhancement of the cardiovascular structures is essential. There is considerable controversy about the administration of contrast medium (CM) in infants and small children, with either a power injector or a manual (hand) injection.The aim of this study was to compare image quality with power injection of CM (study group) and manual injection (control group).Thirty-four patients (study group, 6.8 ± 9.6 months and control group, 4.6 ± 8.9 months, nonrandomized) underwent dual-source CT angiography of the chest using a prospective electrocardiography-triggered high-pitch spiral mode (pitch, 3.4; 80 kV). In the study group (17 patients), a power injector was used, and in the control group (17 patients, historical group), manual CM injection had been performed. To assess image quality, both subjective and objective parameters were evaluated independently by 2 experienced radiologists.Subjective overall image quality, signal-to-noise ratio, and contrast-to-noise ratio were significantly higher using power injection compared with manual injection (P < .05). However, depiction of cardiovascular structures did not differ significantly between both groups in all evaluated regions except the superior vena cava and the coronary arteries.In infants and small children with congenital heart disease, both manual and power injector protocols allowed for diagnostic imaging of cardiac and extracardiac structures. However, image quality and vascular attenuation were superior using a power injector.
EVALuna2:11950

Contribution of the immune system to bystander and non-targeted effects of ionizing radiation - Roedel, Franz; Frey, Benjamin; Multhoff, Gabriele; Gaipl, Udo (Cancer Letters, 2015)
Considerable progress has recently been achieved in the understanding of molecular mechanisms involved in cellular radiation responses and radiation mediated microenvironmental communication. In line with that, it has become more and more obvious that X-irradiation causes distinct immunological effects ranging from anti-inflammatory activities if applied at low (<1 Gy) doses to harmful inflammatory side effects, radiation-induced immune modulation or induction of anti-tumour immune responses at higher doses. Moreover, experimental and clinical evidences indicate that these effects not only originate from direct nuclear damage but also include non-(DNA) targeted mechanisms including bystander, out of field distant bystander (abscopal) effects and genomic instability. The purpose of the present review is to elucidate immune responses that are initiated or affected by ionizing radiation, with a special emphasis on anti-inflammatory and abscopal effects and the induction of stress-induced anti-tumour immunity.
EVALuna2:18184

Correction to expert consensus on re-irradiation for recurrent glioma - Krauze, Andra V.; Attia, Albert; Braunstein, Steve; Chan, Michael; Combs, Stephanie E.; Fietkau, Rainer; Fiveash, John; Flickinger, John; Grosu, Anca; Howard, Steven; Nieder, Carsten; Niyazi, Maximilian; et al. (Radiation Oncology, 2018)
In the original publication [1] two author names were missing the middle names. The corrected versions can be found in this Erratum.
EVALuna2:32860

Correction to: Innovative radiation oncology Together—Precise, Personalized, Human: Vision 2030 for radiotherapy & radiation oncology in Germany (Strahlentherapie und Onkologie, (2021), 197, 12, (1043-1048), 10.1007/s00066-021-01843-9) - Krug, David; Hecht, Markus; Ebert, Nadja; Maurer, Matthias; Fleischmann, Daniel F.; Fokas, Emmanouil; Straube, Christoph; Nicolay, Nils Henrik; Horner-Rieber, Juliane; Schmitt, Daniela; Von Neubeck, Clare; Zamboglou, Constantinos; et al. (Strahlentherapie und Onkologie, 2021)
The original version of this article unfortunately contained mistakes. The name of the author Hess was corrected. Fig. 1 contained orthographic errors. Additionally, to ensure that the hyperlinks embedded in Fig. 1 can be accessed, Fig. 1 was added as Supplement 3. A reference to Supplement 3 has been added in the description of Fig. 1 in the article. The original article has been corrected.
CRIS-Team Scopus Importer:2021-11-26

Correction to: 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 (Strahlentherapie und Onkologie, (2021), 10.1007/s00066-020-01727-4) - 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)
The original version of this article unfortunately contained a mistake. The spelling of M. Trommer’s name was incorrect. The corrected author list is given above. The original article has been corrected.
CRIS-Team Scopus Importer:2021-04-09

Correction to: Recent advances in Surface Guided Radiation Therapy (Radiation Oncology, (2020), 15, 1, (187), 10.1186/s13014-020-01629-w) - Freislederer, P.; Kügele, M.; Öllers, M.; Swinnen, A.; Sauer, Tim-Oliver; Bert, Christoph; Giantsoudi, D.; Corradini, S.; Batista, V. (Radiation Oncology, 2020)
Following publication of the original article [1], the authors identified an error in the order of Figs. 2 and 3. The correct representation of figures is provided below. The original article [1] has been corrected.
CRIS-Team Scopus Importer:2020-10-30