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Jakob, Jens
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Jakob, Jens
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Jakob, Jens
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Jakob, J.
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2021Journal Article [["dc.bibliographiccitation.firstpage","639"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","Biology"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Gaiser, Timo"],["dc.contributor.author","Sauer, Christian"],["dc.contributor.author","Marx, Alexander"],["dc.contributor.author","Jakob, Jens"],["dc.contributor.author","Kasper, Bernd"],["dc.contributor.author","Hohenberger, Peter"],["dc.contributor.author","Hirsch, Daniela"],["dc.contributor.author","Ronellenfitsch, Ulrich"],["dc.date.accessioned","2021-09-01T06:43:07Z"],["dc.date.available","2021-09-01T06:43:07Z"],["dc.date.issued","2021"],["dc.description.abstract","In the framework of the German Interdisciplinary Sarcoma Group GISG-04/NOPASS trial, we evaluated soft tissue sarcoma samples taken before and after neoadjuvant pazopanib therapy using histopathology and next generation sequencing (NGS) to find potential predictive biomarkers. We also aimed to improve the genetically based sarcoma classification and to elucidate additional potentially druggable mutations. In total, 30 tumor samples from 18 patients consisting of 12 pre-therapeutic biopsies and 18 resection specimens following neoadjuvant pazopanib therapy were available for analyses. NGS was performed with the Oncomine Focus Assay (Ion Torrent) covering 0.03 Mb of DNA and enabled the detection of genetic variants in 52 cancer-relevant genes. Pathological analysis showed significant regression (≥50%) after pazopanib treatment in only one undifferentiated (pleomorphic) sarcoma. NGS analyses revealed a very high frequency of CDK4 amplification (88%; 7/8) in the group of dedifferentiated liposarcoma. In addition, two potentially druggable mutations, a MAP2K1 missense mutation (E203K) and a BRAF missense mutation (V600E), were traceable in two undifferentiated (pleomorphic) sarcoma patients (11%; 2/18). Our findings demonstrate that NGS testing is a powerful technology helping to improve diagnostic accuracy and offering some patients the chance for personalized medicine even in a “mutation unlikely” cohort like STS."],["dc.description.abstract","In the framework of the German Interdisciplinary Sarcoma Group GISG-04/NOPASS trial, we evaluated soft tissue sarcoma samples taken before and after neoadjuvant pazopanib therapy using histopathology and next generation sequencing (NGS) to find potential predictive biomarkers. We also aimed to improve the genetically based sarcoma classification and to elucidate additional potentially druggable mutations. In total, 30 tumor samples from 18 patients consisting of 12 pre-therapeutic biopsies and 18 resection specimens following neoadjuvant pazopanib therapy were available for analyses. NGS was performed with the Oncomine Focus Assay (Ion Torrent) covering 0.03 Mb of DNA and enabled the detection of genetic variants in 52 cancer-relevant genes. Pathological analysis showed significant regression (≥50%) after pazopanib treatment in only one undifferentiated (pleomorphic) sarcoma. NGS analyses revealed a very high frequency of CDK4 amplification (88%; 7/8) in the group of dedifferentiated liposarcoma. In addition, two potentially druggable mutations, a MAP2K1 missense mutation (E203K) and a BRAF missense mutation (V600E), were traceable in two undifferentiated (pleomorphic) sarcoma patients (11%; 2/18). Our findings demonstrate that NGS testing is a powerful technology helping to improve diagnostic accuracy and offering some patients the chance for personalized medicine even in a “mutation unlikely” cohort like STS."],["dc.description.sponsorship","Novartis"],["dc.description.sponsorship","GlaxoSmithKline"],["dc.description.sponsorship","Medical Faculty of the Martin-Luther-University Halle-Wittenberg"],["dc.identifier.doi","10.3390/biology10070639"],["dc.identifier.pii","biology10070639"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/89223"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-455"],["dc.publisher","MDPI"],["dc.relation.eissn","2079-7737"],["dc.rights","https://creativecommons.org/licenses/by/4.0/"],["dc.title","Molecular and Pathological Profiling of Corresponding Treatment-Naïve and Neoadjuvant Pazopanib-Treated High-Risk Soft Tissue Sarcoma Samples of the GISG-04/NOPASS Study"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]Details DOI2020Journal Article [["dc.bibliographiccitation.firstpage","3590"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","Cancers"],["dc.bibliographiccitation.volume","12"],["dc.contributor.affiliation","Eichler, Martin; \t\t \r\n\t\t Clinic and Polyclinic for Internal Medicine I, University Hospital Carl Gustav Carus, TU Dresden, 01307 Dresden, Germany, martin.eichler@uniklinikum-dresden.de\t\t \r\n\t\t National Center for Tumor Diseases (NCT/UCC), 01307 Dresden, Germany, martin.eichler@uniklinikum-dresden.de"],["dc.contributor.affiliation","Hentschel, Leopold; \t\t \r\n\t\t National Center for Tumor Diseases (NCT/UCC), 01307 Dresden, Germany, Leopold.Hentschel@uniklinikum-dresden.de"],["dc.contributor.affiliation","Richter, Stephan; \t\t \r\n\t\t Clinic and Polyclinic for Internal Medicine I, University Hospital Carl Gustav Carus, TU Dresden, 01307 Dresden, Germany, stephan.richter@uniklinikum-dresden.de"],["dc.contributor.affiliation","Hohenberger, Peter; \t\t \r\n\t\t Division of Surgical Oncology & Thoracic Surgery, Mannheim University Medical Center, University of Heidelberg, 68167 Mannheim, Germany, peter.hohenberger@umm.de"],["dc.contributor.affiliation","Kasper, Bernd; \t\t \r\n\t\t Interdisciplinary Tumor Center, Sarcoma Unit, University Medical Center Mannheim, 68167 Mannheim, Germany, bernd.kasper@umm.de"],["dc.contributor.affiliation","Andreou, Dimosthenis; \t\t \r\n\t\t Department of General Orthopedics and Tumor Orthopedics, University Hospital Munster, 48149 Munster, Germany, Dimosthenis.andreou@helios-gesundheit.de\t\t \r\n\t\t Sarcoma Center Berlin-Brandenburg, Helios Hospital Bad Saarow, 15526 Bad Saarow, Germany, Dimosthenis.andreou@helios-gesundheit.de"],["dc.contributor.affiliation","Pink, Daniel; \t\t \r\n\t\t Sarcoma Center Berlin-Brandenburg, Helios Hospital Bad Saarow, 15526 Bad Saarow, Germany, daniel.pink@helios-kliniken.de\t\t \r\n\t\t Department of Internal Medicine C, University Hospital Greifswald, 17475 Greifswald, Germany, daniel.pink@helios-kliniken.de"],["dc.contributor.affiliation","Jakob, Jens; \t\t \r\n\t\t Clinic for General, Visceral, and Pediatric Surgery, University Hospital Goettingen, 37075 Goettingen, Germany, jens.jakob@med.uni-goettingen.de"],["dc.contributor.affiliation","Singer, Susanne; \t\t \r\n\t\t Institute for Medical Biostatistics, Epidemiology and Informatic, University Hospital Mainz, 55131 Mainz, Germany, singers@uni-mainz.de"],["dc.contributor.affiliation","Grützmann, Robert; \t\t \r\n\t\t Clinic for Surgery, University Hospital Erlangen, 91054 Erlangen, Germany, Robert.Gruetzmann@uk-erlangen.de"],["dc.contributor.affiliation","Fung, Stephen; \t\t \r\n\t\t Clinic for General, Visceral, and Pediatric Surgery, University Hospital Dusseldorf, 40225 Dusseldorf, Germany, Stephen.Fung@med.uni-duesseldorf.de"],["dc.contributor.affiliation","Wardelmann, Eva; \t\t \r\n\t\t Gerhard-Domagk-Institute for Pathology, University Hospital Munster, 48149 Munster, Germany, eva.wardelmann@ukmuenster.de"],["dc.contributor.affiliation","Arndt, Karin; \t\t \r\n\t\t German Sarcoma Foundation, 61200 Woelfersheim, Germany, Karin.Arndt@sarkome.de"],["dc.contributor.affiliation","Heidt, Vitali; \t\t \r\n\t\t The Scientific Institute of Office-based Hematologists and Oncologists, 50676 Cologne, Germany, heidt@winho.de"],["dc.contributor.affiliation","Hofbauer, Christine; \t\t \r\n\t\t National Center for Tumor Diseases (NCT/UCC), 01307 Dresden, Germany, christine.hofbauer@uniklinikum-dresden.de\t\t \r\n\t\t University Center for Orthopedics and Trauma Surgery, TU Dresden, 01307 Dresden, Germany, christine.hofbauer@uniklinikum-dresden.de"],["dc.contributor.affiliation","Fried, Marius; \t\t \r\n\t\t Clinic and Polyclinic for Internal Medicine III/University-Centre for Tumor Diseases, University Hospital Mainz, 55131 Mainz, Germany, Marius.Fried@unimedizin-mainz.de"],["dc.contributor.affiliation","Gaidzik, Verena I.; \t\t \r\n\t\t Clinic for Internal Medicine III, University Hospital Ulm, 89081 Ulm, Germany, Verena.Gaidzik@uniklinik-ulm.de"],["dc.contributor.affiliation","Verpoort, Karl; \t\t \r\n\t\t Inter-Local Joint Practice, Dres. Verpoort, Wierecky & Brandl, 20259 Hamburg, Germany, k.verpoort@t-online.de"],["dc.contributor.affiliation","Ahrens, Marit; \t\t \r\n\t\t Medical Clinic II, University Hospital Frankfurt, 60590 Frankfurt am Main, Germany, marit.ahrens@kgu.de"],["dc.contributor.affiliation","Weitz, Jürgen; \t\t \r\n\t\t National Center for Tumor Diseases (NCT/UCC), 01307 Dresden, Germany, juergen.weitz@uniklinikum-dresden.de\t\t \r\n\t\t Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, TU Dresden, 01307 Dresden, Germany, juergen.weitz@uniklinikum-dresden.de"],["dc.contributor.affiliation","Schaser, Klaus-Dieter; \t\t \r\n\t\t National Center for Tumor Diseases (NCT/UCC), 01307 Dresden, Germany, Klaus-Dieter.Schaser@uniklinikum-dresden.de\t\t \r\n\t\t University Center for Orthopedics and Trauma Surgery, TU Dresden, 01307 Dresden, Germany, Klaus-Dieter.Schaser@uniklinikum-dresden.de"],["dc.contributor.affiliation","Bornhäuser, Martin; \t\t \r\n\t\t Clinic and Polyclinic for Internal Medicine I, University Hospital Carl Gustav Carus, TU Dresden, 01307 Dresden, Germany, martin.bornhaeuser@uniklinikum-dresden.de\t\t \r\n\t\t National Center for Tumor Diseases (NCT/UCC), 01307 Dresden, Germany, martin.bornhaeuser@uniklinikum-dresden.de"],["dc.contributor.affiliation","Schmitt, Jochen; \t\t \r\n\t\t National Center for Tumor Diseases (NCT/UCC), 01307 Dresden, Germany, jochen.schmitt@uniklinikum-dresden.de\t\t \r\n\t\t Center for Evidence-Based Healthcare, University Hospital Carl Gustav Carus, Technical University Dresden, 01307 Dresden, Germany, jochen.schmitt@uniklinikum-dresden.de"],["dc.contributor.affiliation","Schuler, Markus K.; \t\t \r\n\t\t Clinic and Polyclinic for Internal Medicine I, University Hospital Carl Gustav Carus, TU Dresden, 01307 Dresden, Germany, markus.schuler@helios-gesundheit.de\t\t \r\n\t\t Helios Hospital Emil von Behring, Department of Oncology, 14165 Berlin, Germany, markus.schuler@helios-gesundheit.de"],["dc.contributor.author","Eichler, Martin"],["dc.contributor.author","Hentschel, Leopold"],["dc.contributor.author","Richter, Stephan"],["dc.contributor.author","Hohenberger, Peter"],["dc.contributor.author","Kasper, Bernd"],["dc.contributor.author","Andreou, Dimosthenis"],["dc.contributor.author","Pink, Daniel"],["dc.contributor.author","Jakob, Jens"],["dc.contributor.author","Singer, Susanne"],["dc.contributor.author","Grützmann, Robert"],["dc.contributor.author","Fung, Stephen"],["dc.contributor.author","Wardelmann, Eva"],["dc.contributor.author","Arndt, Karin"],["dc.contributor.author","Heidt, Vitali"],["dc.contributor.author","Hofbauer, Christine"],["dc.contributor.author","Fried, Marius"],["dc.contributor.author","Gaidzik, Verena I."],["dc.contributor.author","Verpoort, Karl"],["dc.contributor.author","Ahrens, Marit"],["dc.contributor.author","Weitz, Jürgen"],["dc.contributor.author","Schaser, Klaus-Dieter"],["dc.contributor.author","Bornhäuser, Martin"],["dc.contributor.author","Schmitt, Jochen"],["dc.contributor.author","Schuler, Markus K."],["dc.contributor.author","the PROSa Study Group, the PROSa Study Group"],["dc.date.accessioned","2021-04-14T08:27:29Z"],["dc.date.available","2021-04-14T08:27:29Z"],["dc.date.issued","2020"],["dc.date.updated","2022-02-09T13:21:42Z"],["dc.description.sponsorship","Deutsche Krebshilfe"],["dc.identifier.doi","10.3390/cancers12123590"],["dc.identifier.eissn","2072-6694"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/82303"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.publisher","MDPI"],["dc.relation.eissn","2072-6694"],["dc.rights","https://creativecommons.org/licenses/by/4.0/"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0/"],["dc.title","The Health-Related Quality of Life of Sarcoma Patients and Survivors in Germany—Cross-Sectional Results of a Nationwide Observational Study (PROSa)"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]Details DOI2019-06-08Journal Article Research Paper [["dc.bibliographiccitation.firstpage","790"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Cancers"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Sachpekidis, Christos"],["dc.contributor.author","Karampinis, Ioannis"],["dc.contributor.author","Jakob, Jens"],["dc.contributor.author","Kasper, Bernd"],["dc.contributor.author","Nowak, Kai"],["dc.contributor.author","Pilz, Lothar"],["dc.contributor.author","Attenberger, Ulrike"],["dc.contributor.author","Gaiser, Timo"],["dc.contributor.author","Derigs, Hans-Günter"],["dc.contributor.author","Schwarzbach, Matthias"],["dc.contributor.author","Hohenberger, Peter"],["dc.contributor.author","Dimitrakopoulou-Strauss, Antonia"],["dc.contributor.author","Ronellenfitsch, Ulrich"],["dc.date.accessioned","2020-11-23T13:31:17Z"],["dc.date.available","2020-11-23T13:31:17Z"],["dc.date.issued","2019-06-08"],["dc.description.abstract","The outcome of high-risk soft tissue sarcoma (STS) is poor with radical surgery being the only potentially curative modality. Pazopanib is a multikinase inhibitor approved for the treatment of metastatic STS. Herein, in terms of the German Interdisciplinary Sarcoma Group (GISG-04/NOPASS) trial, we evaluate the potential role of kinetic analysis of fludeoxyglucose F-18 (18F-FDG) data derived from the application of dynamic positron emission tomography/computed tomography (PET/CT) in response assessment to pazopanib of STS patients scheduled for surgical resection. Sixteen STS patients treated with pazopanib as neoadjuvant therapy before surgery were enrolled in the analysis. All patients underwent dynamic PET/CT prior to and after pazopanib treatment. Data analysis consisted of visual (qualitative) analysis of the PET/CT scans, semi-quantitative evaluation based on standardized uptake value (SUV) calculations, and quantitative analysis of the dynamic 18F-FDG PET data, based on two-tissue compartment modeling. Resection specimens were histopathologically assessed and the percentage of regression grade was recorded in 14/16 patients. Time to tumor relapse/progression was also calculated. In the follow-up, 12/16 patients (75%) were alive without relapse, while four patients (25%) relapsed, among them one patient died. Median histopathological regression was 20% (mean 26%, range 5-70%). The studied population was dichotomized using a histopathological regression grade of 20% as cut-off. Based on this threshold, 10/14 patients (71%) showed partial remission (PR), while stable disease (SD) was seen in the rest 4 evaluable patients (29%). Semi-quantitative evaluation showed no statistically significant change in the widely used PET parameters, SUVaverage and SUVmax. On the other hand, 18F-FDG kinetic analysis revealed a significant decrease in the perfusion-related parameter K1, which reflects the carrier-mediated transport of 18F-FDG from plasma to tumor. This decrease can be considered as a marker in response to pazopanib in STS and could be due to the anti-angiogenic effect of the therapeutic agent."],["dc.identifier.doi","10.3390/cancers11060790"],["dc.identifier.pmid","31181713"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16537"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/68983"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.publisher","MDPI"],["dc.relation.eissn","2072-6694"],["dc.relation.issn","2072-6694"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Neoadjuvant Pazopanib Treatment in High-Risk Soft Tissue Sarcoma: A Quantitative Dynamic 18F-FDG PET/CT Study of the German Interdisciplinary Sarcoma Group"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]Details DOI PMID PMC