Search

Your search keyword '"Stenzinger, A"' showing total 3,080 results
Start Over Author "Stenzinger, A"
3,080 results on '"Stenzinger, A"'

151. Endometrial stromal sarcomas with BCOR‐rearrangement harbor MDM2 amplifications

Author

Felix KF Kommoss, Kenneth TE Chang, Damian Stichel, Ana Banito, David TW Jones, Christoph E Heilig, Stefan Fröhling, Felix Sahm, Albrecht Stenzinger, Wolfgang Hartmann, Gunhild Mechtersheimer, Hans‐Peter Sinn, Dietmar Schmidt, Friedrich Kommoss, Andreas vonDeimling, and Christian Koelsche

Subjects
endometrial stromal sarcoma, MDM2, amplification, BCOR, YWHAE, uterine, Pathology, RB1-214
Abstract

Abstract Recently a novel subtype of endometrial stromal sarcoma (ESS) defined by recurrent genomic alterations involving BCOR has been described (HGESS‐BCOR). We identified a case of HGESS‐BCOR with a ZC3H7B‐BCOR gene fusion, which harbored an amplification of the MDM2 locus. This index case prompted us to investigate MDM2 amplification in four additional cases of HGESS‐BCOR. Tumors were analyzed for MDM2 amplification by array‐based profiling of copy number alterations (CNAs) and fluorescence in situ hybridization (FISH), as well as for MDM2 expression by immunohistochemistry (IHC). Additionally, a cohort of other mesenchymal uterine neoplasms, including 17 low‐grade ESS, 6 classical high‐grade ESS with YWHAE‐rearrangement, 16 uterine tumors resembling ovarian sex cord tumors, 7 uterine leiomyomas and 8 uterine leiomyosarcomas, was analyzed for CNAs in MDM2. Copy number profiling identified amplification of the 12q15 region involving the MDM2 locus in all five HGESS‐BCOR. Subsequent validation analyses of three tumors confirmed MDM2 amplification using MDM2 FISH. Accordingly, IHC showed MDM2 overexpression in all analyzed cases. None of the other uterine neoplasms in our series, including tumors that are in the histopathological differential diagnoses of HGESS‐BCOR, showed copy number gains of MDM2. Together, our results indicate that HGESS‐BCOR carries MDM2 amplifications, which has diagnostic implications and could potentially be used for targeted therapies in these clinically aggressive tumors.

Published
2020
Full Text
View/download PDF

152. The landscape of chromothripsis across adult cancer types

Author

Natalia Voronina, John K. L. Wong, Daniel Hübschmann, Mario Hlevnjak, Sebastian Uhrig, Christoph E. Heilig, Peter Horak, Simon Kreutzfeldt, Andreas Mock, Albrecht Stenzinger, Barbara Hutter, Martina Fröhlich, Benedikt Brors, Arne Jahn, Barbara Klink, Laura Gieldon, Lina Sieverling, Lars Feuerbach, Priya Chudasama, Katja Beck, Matthias Kroiss, Christoph Heining, Lino Möhrmann, Andrea Fischer, Evelin Schröck, Hanno Glimm, Marc Zapatka, Peter Lichter, Stefan Fröhling, and Aurélie Ernst

Subjects
Science
Abstract

The shattering of chromosomes is a dramatic early event in tumourigenesis and is termed chromothripsis. Here, the authors examine chromothripsis across 28 tumour types and show that 49% of cancers exhibit features of chromothripsis.

Published
2020
Full Text
View/download PDF

153. Durvalumab in frail and elderly patients with stage four non-small cell lung cancer: Study protocol of the randomized phase II DURATION trial

Author

Jonas Kuon, Adriane Hommertgen, Johannes Krisam, Felix Lasitschka, Albrecht Stenzinger, Miriam Blasi, Farastuk Bozorgmehr, Martin Maenz, Meinhard Kieser, Marc Schneider, and Michael Thomas

Subjects
Lung cancer, Durvalumab, PD-L1, Elderly, Frail, CARG, Medicine (General), R5-920
Abstract

Abstract Background Elderly patients represent a major fraction of non-small cell lung cancer (NSCLC) patients in routine clinical practice, but they are still underrepresented in clinical trials. In particular, data regarding efficacy and safety in frail or elderly patients with respect to immunotherapy are lacking. Importantly, immunosenescence in elderly patients might interfere with activities of immune-modulating drugs such as PD-1/PD-L1 inhibitors. Thus, there is an urgent need to assess safety and efficacy of such inhibitors in this group. Methods/design This prospective, open label, treatment stratified, randomized phase II study will enroll 200 patients with stage IV NSCLC amenable at least to single-agent chemotherapy (CT). Eligible patients must be aged 70 years or older and/or “frail” (Charlson Comorbidity Index > 1) or have a restricted performance status (Eastern Cooperative Oncology Group, ECOG > 1). Patients are stratified according to modified Cancer and Age Research Group (CARG) score: “fit” patients are allocated to combination CT (carboplatin/nab-paclitaxel) and “less fit” patients receive single-agent CT (gemcitabine or vinorelbine). After allocation to strata, patients are randomized 1:1 to receive either four cycles of CT or two cycles of CT followed by two cycles of durvalumab and subsequent maintenance treatment with durvalumab every 4 weeks. The primary endpoint is the rate of treatment-related grade III/IV adverse events (Common Terminology Criteria for Adverse Events (CTCAE) V4.03). As secondary endpoints, progression-free survival (PFS) according to Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1, response rate (RR), overall survival (OS), descriptive subgroup analyses according to PD-L1 expression, and quality of life are addressed. Geriatric screening assessments and functional tests will be performed to complete the phenotyping of a potential “frail” and “elderly” patient cohort. The trial is accompanied by a biomaterial repository to explore potential biomarkers. Discussion The DURATION trial will prospectively investigate the safety and tolerability of anti-PD-L1 treatment with durvalumab after chemotherapy in elderly and frail patients and thereby provide new insights into the effect of PD-L1 blockade and the impact of immunosenescence in this cohort of patients. Trial registration ClinicalTrials.gov, NCT03345810 ; initially registered on 17 November 2017. Eudra-CT, 2016–003963-20; initially registered on 3 January 2017.

Published
2020
Full Text
View/download PDF

155. Sarcoma classification by DNA methylation profiling

Author

Koelsche, Christian, Schrimpf, Daniel, Stichel, Damian, Sill, Martin, Sahm, Felix, Reuss, David E., Blattner, Mirjam, Worst, Barbara, Heilig, Christoph E., Beck, Katja, Horak, Peter, Kreutzfeldt, Simon, Paff, Elke, Stark, Sebastian, Johann, Pascal, Selt, Florian, Ecker, Jonas, Sturm, Dominik, Pajtler, Kristian W., Reinhardt, Annekathrin, Wefers, Annika K., Sievers, Philipp, Ebrahimi, Azadeh, Suwala, Abigail, Fernández-Klett, Francisco, Casalini, Belén, Korshunov, Andrey, Hovestadt, Volker, Kommoss, Felix K. F., Kriegsmann, Mark, Schick, Matthias, Bewerunge-Hudler, Melanie, Milde, Till, Witt, Olaf, Kulozik, Andreas E., Kool, Marcel, Romero-Pérez, Laura, Grünewald, Thomas G. P., Kirchner, Thomas, Wick, Wolfgang, Platten, Michael, Unterberg, Andreas, Uhl, Matthias, Abdollahi, Amir, Debus, Jürgen, Lehner, Burkhard, Thomas, Christian, Hasselblatt, Martin, Paulus, Werner, Hartmann, Christian, Staszewski, Ori, Prinz, Marco, Hench, Jürgen, Frank, Stephan, Versleijen-Jonkers, Yvonne M. H., Weidema, Marije E., Mentzel, Thomas, Griewank, Klaus, de Álava, Enrique, Martín, Juan Díaz, Gastearena, Miguel A. Idoate, Chang, Kenneth Tou-En, Low, Sharon Yin Yee, Cuevas-Bourdier, Adrian, Mittelbronn, Michel, Mynarek, Martin, Rutkowski, Stefan, Schüller, Ulrich, Mautner, Viktor F., Schittenhelm, Jens, Serrano, Jonathan, Snuderl, Matija, Büttner, Reinhard, Klingebiel, Thomas, Buslei, Rolf, Gessler, Manfred, Wesseling, Pieter, Dinjens, Winand N. M., Brandner, Sebastian, Jaunmuktane, Zane, Lyskjær, Iben, Schirmacher, Peter, Stenzinger, Albrecht, Brors, Benedikt, Glimm, Hanno, Heining, Christoph, Tirado, Oscar M., Sáinz-Jaspeado, Miguel, Mora, Jaume, Alonso, Javier, del Muro, Xavier Garcia, Moran, Sebastian, Esteller, Manel, Benhamida, Jamal K., Ladanyi, Marc, Wardelmann, Eva, Antonescu, Cristina, Flanagan, Adrienne, Dirksen, Uta, Hohenberger, Peter, Baumhoer, Daniel, Hartmann, Wolfgang, Vokuhl, Christian, Flucke, Uta, Petersen, Iver, Mechtersheimer, Gunhild, Capper, David, Jones, David T. W., Fröhling, Stefan, Pfister, Stefan M., and von Deimling, Andreas

Published
2021
Full Text
View/download PDF

157. Role of Synaptophysin, Chromogranin and CD56 in adenocarcinoma and squamous cell carcinoma of the lung lacking morphological features of neuroendocrine differentiation: a retrospective large-scale study on 1170 tissue samples

Author

Kriegsmann, Katharina, Zgorzelski, Christiane, Muley, Thomas, Christopoulos, Petros, Thomas, Michael, Winter, Hauke, Eichhorn, Martin, Eichhorn, Florian, von Winterfeld, Moritz, Herpel, Esther, Goeppert, Benjamin, Stenzinger, Albrecht, Herth, Felix J. F., Warth, Arne, and Kriegsmann, Mark

Published
2021
Full Text
View/download PDF

160. Targetable ERBB2 mutations identified in neurofibroma/schwannoma hybrid nerve sheath tumors

Author

Ronellenfitsch, Michael W., Harter, Patrick N., Kirchner, Martina, Heining, Christoph, Hutter, Barbara, Gieldon, Laura, Schittenhelm, Jens, Schuhmann, Martin U., Tatagiba, Marcos, Wagner, Gerhard Marquard Marlies, Endris, Volker, Brandts, Christian H., Mautner, Victor-Felix, Schrock, Evelin, Weicher, Wilko, Brors, Benedikt, von Deimling, Andreas, Mittelbronn, Michel, Steinbach, Joachim P., Reuss, David E., Glimm, Hanno, Stenzinger, Albrecht, and Frohling, Stefan

Subjects
Merck & Company Inc., Thermo Fisher Scientific Inc., Bayer AG, Bristol-Myers Squibb Co., Novartis AG, AstraZeneca PLC, Lapatinib, Cancer -- Care and treatment -- Genetic aspects, Methylation, Tyrosine -- Genetic aspects, Pharmaceutical industry, Genomics -- Genetic aspects, Neratinib, Scientific equipment industry -- Genetic aspects, Criminal investigation, Cancer research, Neurofibromatosis, Phenols (Class of compounds), Tumors, DNA, Scientists, Research funding, Health care industry
Abstract

BACKGROUND. Neurofibroma/schwannoma hybrid nerve sheath tumors (N/S HNSTs) are neoplasms associated with larger nerves that occur sporadically and in the context of schwannomatosis or neurofibromatosis type 2 or 1. Clinical management of N/S HNSTs is challenging, especially for large tumors, and established systemic treatments are lacking. METHODS. We used next-generation sequencing and array-based DNA methylation profiling to determine the clinically actionable genomic and epigenomic landscapes of N/S HNSTs. RESULTS. Whole-exome sequencing within a precision oncology program identified an activating mutation (p.Asp769Tyr) in the catalytic domain of the ERBB2 receptor tyrosine kinase in a patient with schwannomatosis-associated N/S HNST, and targeted treatment with the small-molecule ERBB inhibitor lapatinib led to prolonged clinical benefit and a lasting radiographic and metabolic response. Analysis of a multicenter validation cohort revealed recurrent ERBB2 mutations (p.Leu755Ser, p.Asp769Tyr, p.Val777Leu) in N/S HNSTs occurring in patients who met diagnostic criteria for sporadic schwannomatosis (3 of 7 patients), but not in N/S HNSTs arising in the context of neurofibromatosis (6 patients) or outside a tumor syndrome (1 patient), and showed that ERBB2-mutant N/S HNSTs cluster in a distinct subgroup of peripheral nerve sheath tumors based on genome-wide DNA methylation patterns. CONCLUSION. These findings uncover a key biological feature of N/S HNSTs that may have important diagnostic and therapeutic implications. FUNDING. This work was supported by grant H021 from DKFZ-HIPO, the University Cancer Center Frankfurt, and the Frankfurt Research Funding Clinician Scientist Program., Introduction Neurofibroma/schwannoma hybrid nerve sheath tumors (N/S HNSTs) are peripheral nerve sheath tumors that are recognized as a distinct entity by the 2016 update of the World Health Organization (WHO) [...]

Published
2020
Full Text
View/download PDF

165. Status der Verfügbarkeit und Anwendung von „next generation sequencing“ (NGS) beim Harnblasenkarzinom – eine Umfrage in der Arbeitsgemeinschaft Uropathologie

Author

Ortiz-Brüchle, N., Muders, M., Toma, M., Esposito, I., Hartmann, A., Stöhr, R., Reis, H., Wild, P., Köllermann, J., Bremmer, F., Leichsenring, J., Stenzinger, A., Merkelbach-Bruse, S., Kirfel, S., Perner, S., Hartmann, N., Roth, W., Jung, A., Kirchner, T., Schwamborn, K., Pfarr, N., Dahl, E., Knüchel, R., and Gaisa, N. T.

Published
2020
Full Text
View/download PDF

166. Identification and characterization of a BRAF fusion oncoprotein with retained autoinhibitory domains

Author

Weinberg, Florian, Griffin, Ricarda, Fröhlich, Martina, Heining, Christoph, Braun, Sandra, Spohr, Corinna, Iconomou, Mary, Hollek, Viola, Röring, Michael, Horak, Peter, Kreutzfeldt, Simon, Warsow, Gregor, Hutter, Barbara, Uhrig, Sebastian, Neumann, Olaf, Reuss, David, Heiland, Dieter Henrik, von Kalle, Christof, Weichert, Wilko, Stenzinger, Albrecht, Brors, Benedikt, Glimm, Hanno, Fröhling, Stefan, and Brummer, Tilman

Published
2020
Full Text
View/download PDF

168. Spatial and Temporal Heterogeneity of Panel-Based Tumor Mutational Burden in Pulmonary Adenocarcinoma: Separating Biology From Technical Artifacts

Author

Kazdal, Daniel, Endris, Volker, Allgäuer, Michael, Kriegsmann, Mark, Leichsenring, Jonas, Volckmar, Anna-Lena, Harms, Alexander, Kirchner, Martina, Kriegsmann, Katharina, Neumann, Olaf, Brandt, Regine, Talla, Suranand B., Rempel, Eugen, Ploeger, Carolin, von Winterfeld, Moritz, Christopoulos, Petros, Merino, Diana M., Stewart, Mark, Allen, Jeff, Bischoff, Helge, Meister, Michael, Muley, Thomas, Herth, Felix, Penzel, Roland, Warth, Arne, Winter, Hauke, Fröhling, Stefan, Peters, Solange, Swanton, Charles, Thomas, Michael, Schirmacher, Peter, Budczies, Jan, and Stenzinger, Albrecht

Published
2019
Full Text
View/download PDF

173. Community-driven development of a modified progression-free survival ratio for precision oncology

Author

Mock, Andreas, Heilig, Christoph E, Kreutzfeldt, Simon, Huebschmann, Daniel, Heining, Christoph, Schröck, Evelin, Brors, Benedikt, Stenzinger, Albrecht, Jäger, Dirk, Schlenk, Richard, Glimm, Hanno, Fröhling, Stefan, Horak, Peter, Apostolidis, Leonidas, Augustin, Marinela, Aust, Daniela, Bhatti, Irfan Ahmed, Bloehdorn, Johannes, Brendel, Cornelia, Britschgi, Christian, Braess, Jan, Burdach, Stefan, Busch, Elena, Casuscelli, Jozefina, Desuki, Alexander, Deutsch, Thomas, Dietrich, Mareike, Ehmer, Ursula, Ettrich, Thomas J, Falkenhorst, Johanna, Fehm, Tanja, Flörcken, Anne, Forschner, Andrea, Fuxius, Stefan, Gonzales-Carmona, Maria, Griesinger, Frank, Grill, Sabine, Gröschel, Stefan, Haag, Georg Martin, Haag, Ulrich, Halama, Niels, Hebart, Holger, Heidger, Nina, Hermes, Barbara, Hess, Georg, Hettmer, Simone, Hoechstetter, Manuela, Hoffmann, Martin, Hüttner, Felix J, Illert, Anna L, Jenzer, Maximilian, Kasper, Bernd, Kasper-Virchow, Stefan, Kindler, Thomas, Koscielniak, Ewa, Krönke, Jan, Kühn, Michael, Kunzmann, Volker, Lang, Alois, Leichsenring, Jonas, Livingstone, Elisabeth, Liotta, Lucia, Luley, Kim, Mack, Elisabeth, Martens, Uwe M, Metzeler, Klaus, Middeke, Jan Moritz, Möhrmann, Lino, Jayarama-Naidu, Roopa, Pape, Ulrich-Frank, Perkhofer, Lukas, Pfeufer, Arne, Pixberg, Constantin, Quante, Michael, Rendenbach, Bernhard, Rieke, Damian, Rothermundt, Christian, Sagerer, Andre Norbert, Salzmann, Martin, Saur, Dieter, Schilling, Bastian, Schleicher, Jan, Schlenska-Lange, Anke, Schmidt, Thomas, Schmitz, Sophia, Schölch, Sebastian, Shah, Rajiv, Shoumariyeh, Khalid, Siebenhüner, Alexander, Singh, Martin, Siveke, Jens, Springfeld, Christoph, Starke, Helen, Strobel, Sophia, Teleanu, Veronica, Thon, Niklas, Wagner, Sebastian, Walle, Thomas, Westphalen, Benedikt, Whitlock, Bettina, Winkler, Eva, Wirsik, Naita Maren, Woydack, Lena, Bois, Angelika Zabel-du, and Zschäbitz, Stefanie

Published
2019
Full Text
View/download PDF

174. Fully Automatic Deep Learning in Bi-institutional Prostate Magnetic Resonance Imaging: Effects of Cohort Size and Heterogeneity

Author

Netzer, Nils, Weißer, Cedric, Schelb, Patrick, Wang, Xianfeng, Qin, Xiaoyan, Görtz, Magdalena, Schütz, Viktoria, Radtke, Jan Philipp, Hielscher, Thomas, Schwab, Constantin, Stenzinger, Albrecht, Kuder, Tristan Anselm, Gnirs, Regula, Hohenfellner, Markus, Schlemmer, Heinz-Peter, Maier-Hein, Klaus H., and Bonekamp, David

Published
2021
Full Text
View/download PDF

177. Outcome of First-Line Treatment With Pembrolizumab According to KRAS/TP53 Mutational Status for Nonsquamous Programmed Death-Ligand 1–High (≥50%) NSCLC in the German National Network Genomic Medicine Lung Cancer.

Author

Bischoff, Philip, Reck, Martin, Overbeck, Tobias, Christopoulos, Petros, Rittmeyer, Achim, Lüders, Heike, Kollmeier, Jens, Kulhavy, Jonas, Kemper, Marcel, Reinmuth, Niels, Röper, Julia, Janning, Melanie, Sommer, Linna, Aguinarte, Lukas, Koch, Myriam, Wiesweg, Marcel, Wesseler, Claas, Waller, Cornelius F., Kauffmann-Guerrero, Diego, and Stenzinger, Albrecht

Published
2024
Full Text
View/download PDF

178. Protocol of the IntenSify‐Trial: An open‐label phase I trial of the CYP3A inhibitor cobicistat and the cytostatics gemcitabine and nab‐paclitaxel in patients with advanced stage or metastatic pancreatic ductal adenocarcinoma to evaluate the combination's pharmacokinetics, safety, and efficacy

Author

Hohmann, Nicolas, primary, Sprick, Martin Ronald, additional, Pohl, Moritz, additional, Ahmed, Azaz, additional, Burhenne, Jürgen, additional, Kirchner, Marietta, additional, Le Cornet, Lucian, additional, Kratzmann, Markus, additional, Hajda, Jacek, additional, Stenzinger, Albrecht, additional, Steindorf, Karen, additional, Delorme, Stefan, additional, Schlemmer, Heinz‐Peter, additional, Riethdorf, Sabine, additional, van Schaik, Ron, additional, Pantel, Klaus, additional, Siveke, Jens, additional, Seufferlein, Thomas, additional, Jäger, Dirk, additional, Haefeli, Walter E., additional, Trumpp, Andreas, additional, and Springfeld, Christoph, additional

Published
2023
Full Text
View/download PDF

179. PL03.07 Invasion or No Invasion, That’s the Question. A Large Reproducibility Study in Pulmonary Adenocarcinoma, Supporting a Modified Classification

Author

Thunnissen, E., primary, Blaauwgeers, H., additional, Filipello, F., additional, Lissenberg-Witte, B., additional, Minami, Y., additional, Noguchi, M., additional, Le Quense, J., additional, Papotti, M.G., additional, Flieder, D., additional, Pelosi, G., additional, Sansano, I., additional, Berezowska, S., additional, Ryška, A., additional, Brcic, L., additional, Motoi, N., additional, Nakatani, Y., additional, Kuempers, C., additional, Hofman, P., additional, Hofman, V., additional, Grotnes Dale, V., additional, Rossi, G., additional, Ambrosi, F., additional, Matsubara, D., additional, Ishikawa, Y., additional, Weynand, B., additional, Calabrese, F., additional, Pezzuto, F., additional, Kern, I., additional, Nicholson, S., additional, Mutka, A.-L., additional, Dacic, S., additional, Beasley, M.B., additional, Arrigoni, G., additional, Timens, W., additional, Ooft, M., additional, Brinkhuis, M., additional, Bulkmans, N., additional, Britstra, R., additional, Vreuls, W., additional, Jones, K., additional, von der Thüsen, J., additional, Hager, H., additional, Perner, S., additional, Moore, D., additional, Leonte, D.G., additional, Al-Janabi, S., additional, Schønau, A., additional, Stenzinger, A., additional, and Kazdal, D., additional

Published
2023
Full Text
View/download PDF

181. Digital Spatial Profiling Identifies the Tumor Periphery as a Highly Active Biological Niche in Clear Cell Renal Cell Carcinoma

Author

Schneider, Felix, primary, Kaczorowski, Adam, additional, Jurcic, Christina, additional, Kirchner, Martina, additional, Schwab, Constantin, additional, Schütz, Viktoria, additional, Görtz, Magdalena, additional, Zschäbitz, Stefanie, additional, Jäger, Dirk, additional, Stenzinger, Albrecht, additional, Hohenfellner, Markus, additional, Duensing, Stefan, additional, and Duensing, Anette, additional

Published
2023
Full Text
View/download PDF

184. Response to “NGS, the New Global Standard?”

Author

Ou, Sai-Hong Ignatius, primary, Hong, Jin-Liern, additional, Christopoulos, Petros, additional, Lin, Huamao M., additional, Vincent, Sylvie, additional, Churchill, Eric N., additional, Soeda, Junpei, additional, Kazdal, Daniel, additional, Thomas, Michael, additional, and Stenzinger, Albrecht, additional

Published
2023
Full Text
View/download PDF

186. P-365 Genetic profiling and drug response analysis in multiple myeloma: insights for personalized treatment approaches

Author

Rapi, Aikaterini, primary, Poos, Alexandra, additional, Angeli-Terzidou, Antonia-Eugenia, additional, Brinkmann, Berit, additional, Baumann, Anja, additional, Rohleder, Jennifer, additional, Kazdal, Daniel, additional, Knoeringer, Katharina, additional, Hundemer, Michael, additional, Stenzinger, Albrecht, additional, Dietrich, Sascha, additional, Souliotis, Vassilis, additional, Weinhold, Niels, additional, and Raab, Marc, additional

Published
2023
Full Text
View/download PDF

187. Practical Guidance on Establishing a Molecular Testing Pathway for Alterations in Homologous Recombination Repair Genes in Clinical Practice for Patients with Metastatic Prostate Cancer

Author

Schostak, Martin, primary, Bradbury, Angela, additional, Briganti, Alberto, additional, Gonzalez, David, additional, Gomella, Leonard, additional, Mateo, Joaquin, additional, Penault-Llorca, Frédérique, additional, Stenzinger, Albrecht, additional, Wyatt, Alexander W., additional, and Bjartell, Anders, additional

Published
2023
Full Text
View/download PDF

190. Defective homologous recombination DNA repair as therapeutic target in advanced chordoma

Author

Stefan Gröschel, Daniel Hübschmann, Francesco Raimondi, Peter Horak, Gregor Warsow, Martina Fröhlich, Barbara Klink, Laura Gieldon, Barbara Hutter, Kortine Kleinheinz, David Bonekamp, Oliver Marschal, Priya Chudasama, Jagoda Mika, Marie Groth, Sebastian Uhrig, Stephen Krämer, Christoph Heining, Christoph E. Heilig, Daniela Richter, Eva Reisinger, Katrin Pfütze, Roland Eils, Stephan Wolf, Christof von Kalle, Christian Brandts, Claudia Scholl, Wilko Weichert, Stephan Richter, Sebastian Bauer, Roland Penzel, Evelin Schröck, Albrecht Stenzinger, Richard F. Schlenk, Benedikt Brors, Robert B. Russell, Hanno Glimm, Matthias Schlesner, and Stefan Fröhling

Subjects
Science
Abstract

Chordomas are rare bone tumors with limited therapeutic options. Here, the authors identify molecular alterations associated with defective homologous recombination DNA repair in advanced chordomas and report prolonged response in a patient treated with a PARP inhibitor, which later acquired resistance due to a newly gained PARP1 mutation.

Published
2019
Full Text
View/download PDF

191. Molecular Subtyping of Invasive Breast Cancer Using a PAM50-Based Multigene Expression Test-Comparison with Molecular-Like Subtyping by Tumor Grade/Immunohistochemistry and Influence on Oncologist’s Decision on Systemic Therapy in a Real-World Setting

Author

Ramona Erber, Miriam Angeloni, Robert Stöhr, Michael P. Lux, Daniel Ulbrich-Gebauer, Enrico Pelz, Agnes Bankfalvi, Kurt W. Schmid, Robert F. H. Walter, Martina Vetter, Christoph Thomssen, Doris Mayr, Frederick Klauschen, Peter Sinn, Karl Sotlar, Katharina Stering, Albrecht Stenzinger, Marius Wunderle, Peter A. Fasching, Matthias W. Beckmann, Oliver Hoffmann, Rainer Kimmig, Nadia Harbeck, Rachel Wuerstlein, Fulvia Ferrazzi, and Arndt Hartmann

Subjects
Prosigna, PAM50, multigene expression analysis, immunohistochemistry, IHC, tumor grade, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract

In intermediate risk hormone receptor (HR) positive, HER2 negative breast cancer (BC), the decision regarding adjuvant chemotherapy might be facilitated by multigene expression tests. In all, 142 intermediate risk BCs were investigated using the PAM50-based multigene expression test Prosigna® in a prospective multicentric study. In 119/142 cases, Prosigna® molecular subtyping was compared with local and two central (C1 and C6) molecular-like subtypes relying on both immunohistochemistry (IHC; HRs, HER2, Ki-67) and IHC + tumor grade (IHC+G) subtyping. According to local IHC, 35.4% were Luminal A-like and 64.6% Luminal B-like subtypes (local IHC+G subtype: 31.9% Luminal A-like; 68.1% Luminal B-like). In contrast to local and C1 subtyping, C6 classified >2/3 of cases as Luminal A-like. Pairwise agreement between Prosigna® subtyping and molecular-like subtypes was fair to moderate depending on molecular-like subtyping method and center. The best agreement was observed between Prosigna® (53.8% Luminal A; 44.5% Luminal B) and C1 surrogate subtyping (Cohen’s kappa = 0.455). Adjuvant chemotherapy was suggested to 44.2% and 88.6% of Prosigna® Luminal A and Luminal B cases, respectively. Out of all Luminal A-like cases (locally IHC/IHC+G subtyping), adjuvant chemotherapy was recommended if Prosigna® testing classified as Prosigna® Luminal A at high / intermediate risk or upgraded to Prosigna® Luminal B.

Published
2022
Full Text
View/download PDF

192. DNA-Methylome–Based Tumor Hypoxia Classifier Identifies HPV-Negative Head and Neck Cancer Patients at Risk for Locoregional Recurrence after Primary Radiochemotherapy

Author

Bouchra Tawk, Katrin Rein, Christian Schwager, Maximilian Knoll, Ute Wirkner, Juliane Hörner-Rieber, Jakob Liermann, Ina Kurth, Panagiotis Balermpas, Claus Rödel, Annett Linge, Steffen Löck, Fabian Lohaus, Ingeborg Tinhofer, Mechtild Krause, Martin Stuschke, Anca Ligia Grosu, Daniel Zips, Stephanie E. Combs, Claus Belka, Albrecht Stenzinger, Christel Herold-Mende, Michael Baumann, Peter Schirmacher, Jürgen Debus, and Amir Abdollahi

Subjects
Cancer Research, Oncology
Abstract

Purpose: Tumor hypoxia is a paradigmatic negative prognosticator of treatment resistance in head and neck squamous cell carcinoma (HNSCC). The lack of robust and reliable hypoxia classifiers limits the adaptation of stratified therapies. We hypothesized that the tumor DNA methylation landscape might indicate epigenetic reprogramming induced by chronic intratumoral hypoxia. Experimental Design: A DNA-methylome–based tumor hypoxia classifier (Hypoxia-M) was trained in the TCGA (The Cancer Genome Atlas)-HNSCC cohort based on matched assignments using gene expression–based signatures of hypoxia (Hypoxia-GES). Hypoxia-M was validated in a multicenter DKTK-ROG trial consisting of human papillomavirus (HPV)–negative patients with HNSCC treated with primary radiochemotherapy (RCHT). Results: Although hypoxia-GES failed to stratify patients in the DKTK-ROG, Hypoxia-M was independently prognostic for local recurrence (HR, 4.3; P = 0.001) and overall survival (HR, 2.34; P = 0.03) but not distant metastasis after RCHT in both cohorts. Hypoxia-M status was inversely associated with CD8 T-cell infiltration in both cohorts. Hypoxia-M was further prognostic in the TCGA-PanCancer cohort (HR, 1.83; P = 0.04), underscoring the breadth of this classifier for predicting tumor hypoxia status. Conclusions: Our findings highlight an unexplored avenue for DNA methylation–based classifiers as biomarkers of tumoral hypoxia for identifying high-risk features in patients with HNSCC tumors.

Published
2023

193. A phase 2 clinical trial of combined BRAF/MEK inhibition for BRAFV600E-mutated multiple myeloma

Author

Nicola Giesen, Manik Chatterjee, Christof Scheid, Alexandra M. Poos, Britta Besemer, Kaya Miah, Axel Benner, Nicole Becker, Thomas Moehler, Ivana Metzler, Cyrus Khandanpour, Andrea Seidel-Glaetzer, Karolin Trautmann-Grill, K. Martin Kortüm, Carsten Müller-Tidow, Gunhild Mechtersheimer, Benjamin Goeppert, Albrecht Stenzinger, Niels Weinhold, Hartmut Goldschmidt, Katja Weisel, and Marc S. Raab

Subjects
Immunology, Cell Biology, Hematology, Biochemistry
Abstract

Activating BRAF mutations are found in a small subset of patients with newly diagnosed multiple myeloma, but prevalence increases in late-stage, refractory disease, and the mutations are associated with adverse outcome. This prospective single-arm, open-label, multicenter phase 2 trial assessed the efficacy and safety of combined BRAF/MEK inhibition, using encorafenib and binimetinib, in patients with relapsed/refractory multiple myeloma (RRMM) carrying a BRAFV600E mutation. Patients received 450 mg encorafenib once daily and binimetinib 45 mg twice daily. The primary end point was the overall response rate achieved within the first year after start of treatment according to International Myeloma Working Group criteria. Twelve RRMM patients with a median of 5 prior lines of therapy were enrolled. The overall response rate was 83.3%, with 10 patients achieving at least a partial response. The median progression-free survival was 5.6 months, and overall survival was 55% at 24 months. Emerging resistance to therapy was driven by RAS mutations and structural variants involving the BRAF locus. This is the first prospective clinical trial to demonstrate that combined BRAF/MEK inhibition is highly effective in patients with BRAFV600E-mutated RRMM, and it represents a successful targeted precision medicine approach in this disease. This trial was registered at www.clinicaltrials.gov as #NCT02834364.

Published
2023

198. A gene expression signature associated with B cells predicts benefit from immune checkpoint blockade in lung adenocarcinoma

Author

Jan Budczies, Martina Kirchner, Klaus Kluck, Daniel Kazdal, Julia Glade, Michael Allgäuer, Mark Kriegsmann, Claus-Peter Heußel, Felix J. Herth, Hauke Winter, Michael Meister, Thomas Muley, Stefan Fröhling, Solange Peters, Barbara Seliger, Peter Schirmacher, Michael Thomas, Petros Christopoulos, and Albrecht Stenzinger

Subjects
lung adenocarcinoma, immune checkpoint blockade, mrna expression, b cells, tumor-infiltrating lymphocytes, response prediction, Immunologic diseases. Allergy, RC581-607, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Immune checkpoint blockade (ICB) expands the therapeutic options for metastatic lung cancer nowadays representing a standard frontline strategy as monotherapy or combination therapy, as well as an option in oncogene-addicted NSCLC after exhaustion of targeted therapies. Predictive markers are urgently needed, since only a minority of patients benefits from ICB, while serious adverse effects of immunotoxicity may occur. The study cohort included 43 ICB-treated metastatic lung adenocarcinoma showing long-term response (n = 16), rapid progression (n = 21) or intermediate patterns of response (n = 6). Lung biopsies acquired before initiation of ICB were analyzed by targeted mRNA expression profiling of 770 genes. Level and proportions of 14 immune cell types were estimated using characteristic gene expression signatures. Abundance of B cells (HR = 0.66, p = .00074), CD45+ cells (HR = 0.61, p = .01) and total TILs (HR = 0.62, p = .025) was associated with prolonged progression-free survival after ICB treatment. In a ROC analysis, B cells (AUC = 0.77, p = .0055) and CD45+ cells (AUC = 0.73, p = .019) predicted benefit of ICB, which was not the case for PD-L1 mRNA (AUC = 0.54, p = .72) and PD-L1 protein expression (AUC = 0.68, p = .082). Clustering of 79 candidate predictive markers identified among 770 investigated genes revealed two distinct predictive clusters which included cytotoxic cell or macrophage markers, respectively. In summary, targeted gene expression profiling was feasible using routine diagnostics biopsies. This study proposes B cells and total TILs as complementary predictors of ICB benefit in NSCLC. While further preferably prospective validation is required, gene expression profiling could be integrated in the routine diagnostic work-up complementing existing NGS protocols.

Published
2021
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results