TY - JOUR A1 - Klement, Rainer J. A1 - Abbasi-Senger, N. A1 - Adebahr, S. A1 - Alheid, H. A1 - Allgaeuer, M. A1 - Becker, G. A1 - Blanck, O. A1 - Boda-Heggemann, J. A1 - Brunner, T. A1 - Duma, M. A1 - Eble, M. J. A1 - Ernst, I. A1 - Gerum, S. A1 - Habermehl, D. A1 - Hass, P. A1 - Henkenberens, C. A1 - Hildebrandt, G. A1 - Imhoff, D. A1 - Kahl, H. A1 - Klass, N. D. A1 - Krempien, R. A1 - Lewitzki, V. A1 - Lohaus, F. A1 - Ostheimer, C. A1 - Papachristofilou, A. A1 - Petersen, C. A1 - Rieber, J. A1 - Schneider, T. A1 - Schrade, E. A1 - Semrau, R. A1 - Wachter, S. A1 - Wittig, A. A1 - Guckenberger, M. A1 - Andratschke, N. T1 - The impact of local control on overall survival after stereotactic body radiotherapy for liver and lung metastases from colorectal cancer: a combined analysis of 388 patients with 500 metastases JF - BMC Cancer N2 - Background The aim of this analysis was to model the effect of local control (LC) on overall survival (OS) in patients treated with stereotactic body radiotherapy (SBRT) for liver or lung metastases from colorectal cancer. Methods The analysis is based on pooled data from two retrospective SBRT databases for pulmonary and hepatic metastases from 27 centers from Germany and Switzerland. Only patients with metastases from colorectal cancer were considered to avoid histology as a confounding factor. An illness-death model was employed to model the relationship between LC and OS. Results Three hundred eighty-eight patients with 500 metastatic lesions (lung n = 209, liver n = 291) were included and analyzed. Median follow-up time for local recurrence assessment was 12.1 months. Ninety-nine patients with 112 lesions experienced local failure. Seventy-one of these patients died after local failure. Median survival time was 27.9 months in all patients and 25.4 months versus 30.6 months in patients with and without local failure after SBRT. The baseline risk of death after local failure exceeds the baseline risk of death without local failure at 10 months indicating better survival with LC. Conclusion In CRC patients with lung or liver metastases, our findings suggest improved long-term OS by achieving metastatic disease control using SBRT in patients with a projected OS estimate of > 12 months. KW - colorectal cancer KW - illness-death model KW - liver metastases KW - lung metastases KW - tumor control probability KW - stereotactic body radiation therapy Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-325877 VL - 19 ER - TY - JOUR A1 - Barlinn, J. A1 - Winzer, S. A1 - Worthmann, H. A1 - Urbanek, C. A1 - Häusler, K. G. A1 - Günther, A. A1 - Erdur, H. A1 - Görtler, M. A1 - Busetto, L. A1 - Wojciechowski, C. A1 - Schmitt, J. A1 - Shah, Y. A1 - Büchele, B. A1 - Sokolowski, P. A1 - Kraya, T. A1 - Merkelbach, S. A1 - Rosengarten, B. A1 - Stangenberg-Gliss, K. A1 - Weber, J. A1 - Schlachetzki, F. A1 - Abu-Mugheisib, M. A1 - Petersen, M. A1 - Schwartz, A. A1 - Palm, F. A1 - Jowaed, A. A1 - Volbers, B. A1 - Zickler, P. A1 - Remi, J. A1 - Bardutzky, J. A1 - Bösel, J. A1 - Audebert, H. J. A1 - Hubert, G. J. A1 - Gumbinger, C. T1 - Telemedizin in der Schlaganfallversorgung – versorgungsrelevant für Deutschland T1 - Telemedicine in stroke—pertinent to stroke care in Germany JF - Der Nervenarzt N2 - Hintergrund und Ziel Telemedizinische Schlaganfall-Netzwerke tragen dazu bei, die Schlaganfallversorgung und insbesondere den Zugang zu zeitkritischen Schlaganfalltherapien in vorrangig strukturschwachen, ländlichen Regionen zu gewährleisten. Ziel ist eine Darstellung der Nutzungsfrequenz und regionalen Verteilung dieser Versorgungsstruktur. Methoden Die Kommission „Telemedizinische Schlaganfallversorgung“ der Deutschen Schlaganfall-Gesellschaft führte eine Umfragestudie in allen Schlaganfall-Netzwerken durch. Ergebnisse In Deutschland sind 22 telemedizinische Schlaganfall-Netzwerke aktiv, welche insgesamt 43 Zentren (pro Netzwerk: Median 1,5, Interquartilsabstand [IQA] 1–3) sowie 225 Kooperationskliniken (pro Netzwerk: Median 9, IQA 4–17) umfassen und an einem unmittelbaren Zugang zur Schlaganfallversorgung für 48 Mio. Menschen teilhaben. Im Jahr 2018 wurden 38.211 Telekonsile (pro Netzwerk: Median 1340, IQA 319–2758) durchgeführt. Die Thrombolyserate betrug 14,1 % (95 %-Konfidenzintervall 13,6–14,7 %), eine Verlegung zur Thrombektomie wurde bei 7,9 % (95 %-Konfidenzintervall 7,5–8,4 %) der ischämischen Schlaganfallpatienten initiiert. Das Finanzierungssystem ist uneinheitlich mit einem Vergütungssystem für die Zentrumsleistungen in nur drei Bundesländern. Diskussion Etwa jeder 10. Schlaganfallpatient wird telemedizinisch behandelt. Die telemedizinischen Schlaganfall-Netzwerke erreichen vergleichbar hohe Lyseraten und Verlegungen zur Thrombektomie wie neurologische Stroke-Units und tragen zur Sicherstellung einer flächendeckenden Schlaganfallversorgung bei. Eine netzwerkübergreifende Sicherstellung der Finanzierung und einheitliche Erhebung von Qualitätssicherungsdaten haben das Potenzial diese Versorgungsstruktur zukünftig weiter zu stärken. N2 - Background and objective Telemedical stroke networks improve stroke care and provide access to time-dependent acute stroke treatment in predominantly rural regions. The aim is a presentation of data on its utility and regional distribution. Methods The working group on telemedical stroke care of the German Stroke Society performed a survey study among all telestroke networks. Results Currently, 22 telemedical stroke networks including 43 centers (per network: median 1.5, interquartile range, IQR, 1–3) as well as 225 cooperating hospitals (per network: median 9, IQR 4–17) operate in Germany and contribute to acute stroke care delivery to 48 million people. In 2018, 38,211 teleconsultations (per network: median 1340, IQR 319–2758) were performed. The thrombolysis rate was 14.1% (95% confidence interval 13.6–14.7%) and transfer for thrombectomy was initiated in 7.9% (95% confidence interval 7.5–8.4%) of ischemic stroke patients. Financial reimbursement differs regionally with compensation for telemedical stroke care in only three federal states. Conclusion Telemedical stroke care is utilized in about 1 out of 10 stroke patients in Germany. Telemedical stroke networks achieve similar rates of thrombolysis and transfer for thrombectomy compared with neurological stroke units and contribute to stroke care in rural regions. Standardization of network structures, financial assurance and uniform quality measurements may further strengthen the importance of telestroke networks in the future. KW - Schlaganfall KW - Stroke-Unit KW - Telemedizin KW - Schlaganfall-Netzwerk KW - Umfragestudie KW - stroke KW - stroke unit KW - telemedicine KW - stroke networks KW - survey Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-307752 SN - 0028-2804 SN - 1433-0407 VL - 92 IS - 6 ER - TY - JOUR A1 - Andratschke, N. A1 - Alheid, H. A1 - Allgäuer, M. A1 - Becker, G. A1 - Blanck, O. A1 - Boda-Heggemann, J. A1 - Brunner, T. A1 - Duma, M. A1 - Gerum, S. A1 - Guckenberger, M. A1 - Hildebrandt, G. A1 - Klement, R. J. A1 - Lewitzki, V. A1 - Ostheimer, C. A1 - Papachristofilou, A. A1 - Petersen, C. A1 - Schneider, T. A1 - Semrau, R. A1 - Wachter, S. A1 - Habermehl, D. T1 - The SBRT database initiative of the German Society for Radiation Oncology (DEGRO): patterns of care and outcome analysis of stereotactic body radiotherapy (SBRT) for liver oligometastases in 474 patients with 623 metastases JF - BMC Cancer N2 - Background The intent of this pooled analysis as part of the German society for radiation oncology (DEGRO) stereotactic body radiotherapy (SBRT) initiative was to analyze the patterns of care of SBRT for liver oligometastases and to derive factors influencing treated metastases control and overall survival in a large patient cohort. Methods From 17 German and Swiss centers, data on all patients treated for liver oligometastases with SBRT since its introduction in 1997 has been collected and entered into a centralized database. In addition to patient and tumor characteristics, data on immobilization, image guidance and motion management as well as dose prescription and fractionation has been gathered. Besides dose response and survival statistics, time trends of the aforementioned variables have been investigated. Results In total, 474 patients with 623 liver oligometastases (median 1 lesion/patient; range 1–4) have been collected from 1997 until 2015. Predominant histologies were colorectal cancer (n = 213 pts.; 300 lesions) and breast cancer (n = 57; 81 lesions). All centers employed an SBRT specific setup. Initially, stereotactic coordinates and CT simulation were used for treatment set-up (55%), but eventually were replaced by CBCT guidance (28%) or more recently robotic tracking (17%). High variance in fraction (fx) number (median 1 fx; range 1–13) and dose per fraction (median: 18.5 Gy; range 3–37.5 Gy) was observed, although median BED remained consistently high after an initial learning curve. Median follow-up time was 15 months; median overall survival after SBRT was 24 months. One- and 2-year treated metastases control rate of treated lesions was 77% and 64%; if maximum isocenter biological equivalent dose (BED) was greater than 150 Gy EQD2Gy, it increased to 83% and 70%, respectively. Besides radiation dose colorectal and breast histology and motion management methods were associated with improved treated metastases control. Conclusion After an initial learning curve with regards to total cumulative doses, consistently high biologically effective doses have been employed translating into high local tumor control at 1 and 2 years. The true impact of histology and motion management method on treated metastases control deserve deeper analysis. Overall survival is mainly influenced by histology and metastatic tumor burden. KW - stereotactic body radiotherapy KW - liver oligometastases KW - outcome KW - treated metastases control KW - oligometastases KW - oligo-recurrence KW - sync-oligometastases Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-221116 VL - 18 ER - TY - JOUR A1 - Frank, Benjamin A1 - Marcu, Ana A1 - de Oliveira Almeida Petersen, Antonio Luis A1 - Weber, Heike A1 - Stigloher, Christian A1 - Mottram, Jeremy C. A1 - Scholz, Claus Jürgen A1 - Schurigt, Uta T1 - Autophagic digestion of Leishmania major by host macrophages is associated with differential expression of BNIP3, CTSE, and the miRNAs miR-101c, miR-129, and miR-210 JF - Parasites & Vectors N2 - Background Autophagy participates in innate immunity by eliminating intracellular pathogens. Consequently, numerous microorganisms have developed strategies to impair the autophagic machinery in phagocytes. In the current study, interactions between Leishmania major (L. m.) and the autophagic machinery of bone marrow-derived macrophages (BMDM) were analyzed. Methods BMDM were generated from BALB/c mice, and the cells were infected with L. m. promastigotes. Transmission electron microscopy (TEM) and electron tomography were used to investigate the ultrastructure of BMDM and the intracellular parasites. Affymetrix® chip analyses were conducted to identify autophagy-related messenger RNAs (mRNAs) and microRNAs (miRNAs). The protein expression levels of autophagy related 5 (ATG5), BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3), cathepsin E (CTSE), mechanistic target of rapamycin (MTOR), microtubule-associated proteins 1A/1B light chain 3B (LC3B), and ubiquitin (UB) were investigated through western blot analyses. BMDM were transfected with specific small interfering RNAs (siRNAs) against autophagy-related genes and with mimics or inhibitors of autophagy-associated miRNAs. The infection rates of BMDM were determined by light microscopy after a parasite-specific staining. Results The experiments demonstrated autophagy induction in BMDM after in vitro infection with L. m.. The results suggested a putative MTOR phosphorylation-dependent counteracting mechanism in the early infection phase and indicated that intracellular amastigotes were cleared by autophagy in BMDM in the late infection phase. Transcriptomic analyses and specific downregulation of protein expression with siRNAs suggested there is an association between the infection-specific over expression of BNIP3, as well as CTSE, and the autophagic activity of BMDM. Transfection with mimics of mmu-miR-101c and mmu-miR-129-5p, as well as with an inhibitor of mmu-miR-210-5p, demonstrated direct effects of the respective miRNAs on parasite clearance in L. m.-infected BMDM. Furthermore, Affymetrix® chip analyses revealed a complex autophagy-related RNA network consisting of differentially expressed mRNAs and miRNAs in BMDM, which indicates high glycolytic and inflammatory activity in the host macrophages. Conclusions Autophagy in L. m.-infected host macrophages is a highly regulated cellular process at both the RNA level and the protein level. Autophagy has the potential to clear parasites from the host. The results obtained from experiments with murine host macrophages could be translated in the future to develop innovative and therapeutic antileishmanial strategies for human patients. KW - autophagy KW - BNIP3 KW - CTSE KW - electron tomography KW - leishmania major KW - macrophages KW - miRNAs KW - MTOR KW - siRNAs KW - transmission electron microscopy Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-124997 VL - 8 IS - 404 ER -