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5. Mechanism of sensor kinase CitA transmembrane signaling

Author

Xizhou Cecily Zhang, Kai Xue, Michele Salvi, Benjamin Schomburg, Jonas Mehrens, Karin Giller, Marius Stopp, Siegfried Weisenburger, Daniel Böning, Vahid Sandoghdar, Gottfried Unden, Stefan Becker, Loren B. Andreas, and Christian Griesinger

Subjects
Science
Abstract

Abstract Membrane bound histidine kinases (HKs) are ubiquitous sensors of extracellular stimuli in bacteria. However, a uniform structural model is still missing for their transmembrane signaling mechanism. Here, we used solid-state NMR in conjunction with crystallography, solution NMR and distance measurements to investigate the transmembrane signaling mechanism of a paradigmatic citrate sensing membrane embedded HK, CitA. Citrate binding in the sensory extracytoplasmic PAS domain (PASp) causes the linker to transmembrane helix 2 (TM2) to adopt a helical conformation. This triggers a piston-like pulling of TM2 and a quaternary structure rearrangement in the cytosolic PAS domain (PASc). Crystal structures of PASc reveal both anti-parallel and parallel dimer conformations. An anti-parallel to parallel transition upon citrate binding agrees with interdimer distances measured in the lipid embedded protein using a site-specific 19F label in PASc. These data show how Angstrom scale structural changes in the sensor domain are transmitted across the membrane to be converted and amplified into a nm scale shift in the linker to the phosphorylation subdomain of the kinase.

Published
2025
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6. Lipidic folding pathway of α-Synuclein via a toxic oligomer

Author

Vrinda Sant, Dirk Matthes, Hisham Mazal, Leif Antonschmidt, Franz Wieser, Kumar T. Movellan, Kai Xue, Evgeny Nimerovsky, Marianna Stampolaki, Magdeline Nathan, Dietmar Riedel, Stefan Becker, Vahid Sandoghdar, Bert L. de Groot, Christian Griesinger, and Loren B. Andreas

Subjects
Science
Abstract

Abstract Aggregation intermediates play a pivotal role in the assembly of amyloid fibrils, which are central to the pathogenesis of neurodegenerative diseases. The structures of filamentous intermediates and mature fibrils are now efficiently determined by single-particle cryo-electron microscopy. By contrast, smaller pre-fibrillar α-Synuclein (αS) oligomers, crucial for initiating amyloidogenesis, remain largely uncharacterized. We report an atomic-resolution structural characterization of a toxic pre-fibrillar aggregation intermediate (I1) on pathway to the formation of lipidic fibrils, which incorporate lipid molecules on protofilament surfaces during fibril growth on membranes. Super-resolution microscopy reveals a tetrameric state, providing insights into the early oligomeric assembly. Time resolved nuclear magnetic resonance (NMR) measurements uncover a structural reorganization essential for the transition of I1 to mature lipidic L2 fibrils. The reorganization involves the transformation of anti-parallel β-strands during the pre-fibrillar I1 state into a β-arc characteristic of amyloid fibrils. This structural reconfiguration occurs in a conserved structural kernel shared by a vast number of αS-fibril polymorphs including extracted fibrils from Parkinson’s and Lewy Body Dementia patients. Consistent with reports of anti-parallel β-strands being a defining feature of toxic αS pre-fibrillar intermediates, I1 impacts viability of neuroblasts and disrupts cell membranes, resulting in an increased calcium influx. Our results integrate the occurrence of anti-parallel β-strands as salient features of toxic oligomers with their significant role in the amyloid fibril assembly pathway. These structural insights have implications for the development of therapies and biomarkers.

Published
2025
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7. LEVERAGING LOCAL DATA to BOOST STUDENT GROWTH

Author

Griesinger, Matt, Haines, Chris, Lamb, Pat, and Nausadis, Matt

Subjects
Academic achievement -- Methods -- Evaluation, Vocational education -- Methods -- Curricula, Educational reform -- Management, Company business management, Education
Abstract

Change often feels like the only constant that we can count on. And while there are some things we expect to change every year--rosters, materials, even locations--some changes occur without [...]

Published
2024

10. Evolutionary trajectories of small cell lung cancer under therapy

Author

George, Julie, Maas, Lukas, Abedpour, Nima, Cartolano, Maria, Kaiser, Laura, Fischer, Rieke N., Scheel, Andreas H., Weber, Jan-Philipp, Hellmich, Martin, Bosco, Graziella, Volz, Caroline, Mueller, Christian, Dahmen, Ilona, John, Felix, Alves, Cleidson Padua, Werr, Lisa, Panse, Jens Peter, Kirschner, Martin, Engel-Riedel, Walburga, Jürgens, Jessica, Stoelben, Erich, Brockmann, Michael, Grau, Stefan, Sebastian, Martin, Stratmann, Jan A., Kern, Jens, Hummel, Horst-Dieter, Hegedüs, Balazs, Schuler, Martin, Plönes, Till, Aigner, Clemens, Elter, Thomas, Toepelt, Karin, Ko, Yon-Dschun, Kurz, Sylke, Grohé, Christian, Serke, Monika, Höpker, Katja, Hagmeyer, Lars, Doerr, Fabian, Hekmath, Khosro, Strapatsas, Judith, Kambartel, Karl-Otto, Chakupurakal, Geothy, Busch, Annette, Bauernfeind, Franz-Georg, Griesinger, Frank, Luers, Anne, Dirks, Wiebke, Wiewrodt, Rainer, Luecke, Andrea, Rodermann, Ernst, Diel, Andreas, Hagen, Volker, Severin, Kai, Ullrich, Roland T., Reinhardt, Hans Christian, Quaas, Alexander, Bogus, Magdalena, Courts, Cornelius, Nürnberg, Peter, Becker, Kerstin, Achter, Viktor, Büttner, Reinhard, Wolf, Jürgen, Peifer, Martin, and Thomas, Roman K.

Published
2024
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11. Chemoselective umpolung of thiols to episulfoniums for cysteine bioconjugation

Author

Hartmann, Philipp, Bohdan, Kostiantyn, Hommrich, Moritz, Juliá, Fabio, Vogelsang, Lara, Eirich, Jürgen, Zangl, Rene, Farès, Christophe, Jacobs, Julia Beatrice, Mukhopadhyay, Dwaipayan, Mengeler, Johanna Marie, Vetere, Alessandro, Sterling, Marie Sophie, Hinrichs, Heike, Becker, Stefan, Morgner, Nina, Schrader, Wolfgang, Finkemeier, Iris, Dietz, Karl-Josef, Griesinger, Christian, and Ritter, Tobias

Published
2024
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12. Phase III KEYNOTE-789 Study of Pemetrexed and Platinum With or Without Pembrolizumab for Tyrosine Kinase Inhibitor[FIGURE DASH]Resistant, EGFR–Mutant, Metastatic Nonsquamous Non–Small Cell Lung Cancer

Author

Yang, James Chih-Hsin, Lee, Dae Ho, Lee, Jong-Seok, Fan, Yun, de Marinis, Filippo, Iwama, Eiji, Inoue, Takako, Rodríguez-Cid, Jerónimo, Zhang, Li, Yang, Cheng-Ta, de la Mora Jimenez, Emmanuel, Zhou, Jianying, Pérol, Maurice, Lee, Ki Hyeong, Vicente, David, Ichihara, Eiki, Riely, Gregory J., Luo, Yiwen, Chirovsky, Diana, Pietanza, M. Catherine, Bhagwati, Niyati, Lu, Shun, Joseph Boyer, Michael, Hui, Rina, Wong, Mark, Mant, Andrew, Parente, Phillip, John, Thomas, Parakh, Sagun, Castro, Gilberto, Jr, Werutsky, Gustavo, de Azevedo, Sergio Jobim, Andre Franke, Fabio, De Almeida Rego, Joilda Batista, Martins De Marchi, Pedro Rafael, Dix Junqueira, Gustavo, Maris Peria, Fernanda, Brust, Leandro, Cheema, Parneet, Doherty, Mark, Parmar, Ambika, Menjak, Ines B., Leighl, Natasha B., Agulnik, Jason, Lu, Shun, Han, Zhigang, Cui, Jiuwei, Zhang, Li, Cheng, Ying, Chen, Gongyan, Zhang, Helong, Yao, Yu, Hu, Chengping, Wang, Qiming, Zhang, Xin, Zhang, Yong, Zhou, Jianying, Ying, Kejing, Fan, Yun, Wang, Yan, Wang, Ziping, Feng, Jifeng, Du, YingYing, Wu, Lin, Huang, Cheng, Zhou, Xiangdong, Perol, Maurice, Domont, Julien, Lamour, Corinne, Dutilh, Julien, Oulkhouir, Youssef, Westeel, Virginie, Carmier, Delphine, Coudert, Bruno, Lagrange, Aurelie, Spaeth, Dominique, Ropert, Stanislas, Christoph, Daniel C., Kern, Jens, Kopp, Hans-Georg, Griesinger, Frank, Wiewrodt, Rainer, Wermke, Martin, Wesseler, Claas, Mueller, Annette, Vogel, Gunther, Lee, Victor, James Ho, Chung Man, Oscar Chan, Siu Hong, Hung Lo, Sing, Jonathan Nyaw, Shi Feng, Jacky Li, Yu Chung, Bar, Jair, Gottfried, Maya, Dudnik, Julia, Zer, Alona, Moskovitz, Mor, Wollner, Mirjana, Rotem, Ofer, Shamai, Sivan, Asna, Noam, Kamel, Mhameed, Novello, Silvia, Di Costanzo, Francesco, Doni, Laura, Mazzoni, Francesca, Ferrau, Francesco, de Marinis, Filippo, Tonini, Giuseppe, Galetta, Domenico, Piantedosi, Francovito, Vitiello, Fabiana, Kirita, Keisuke, Yoh, Kiyotaka, Takahashi, Toshiaki, Ohe, Yuichiro, Hattori, Yoshihiro, Okamoto, Isamu, Kurata, Takayasu, Yoshioka, Hiroshige, Saka, Hideo, Oki, Masahide, Kato, Terufumi, Tanaka, Hiroshi, Kumagai, Toru, Inoue, Takako, Hida, Toyoaki, Horio, Yoshitsugu, Teraoka, Shunsuke, Ichihara, Eiki, Kishi, Kazuma, Takaya, Hisashi, Takai, Daiya, Kozuki, Toshiyuki, Kasahara, Kazuo, Tambo, Yuichi, Hosomi, Yukio, Kondo, Masashi, Ichiki, Masao, Takeoka, Hiroaki, de la Mora Jimenez, Emmanuel, Hernandez, Carlos Alberto, Rodriguez Cid, Jeronimo Rafael, Rodriguez, Oscar Gerardo Arrieta, Han, Ji-Youn, Min, Young Joo, Kim, Dong-Wan, Park, Keunchil, Lee, Se-Hoon, Lee, Ki Hyeong, Lee, Jong-Seok, Kang, Jin Hyoung, Lee, Dae Ho, Cho, Eun Kyung, Carcereny, Enric, Lopez, Pilar Garrido, Tarruella, Margarita Majem, Rodriguez, Luis Paz-Ares, Vicente Baz, David, Font, Enriqueta Felip, Cobo-Dols, Manuel, Ekman, Simon, Bergman, Bengt, Ohman, Ronny, Vikstrom, Anders, Yang, Chih-Hsin, Chiu, Chao-Hua, Huang, Hsu-Ching, Yang, Cheng-Ta, Su, Jian, Chang, Gee-Chen, Yang, Tsung-Ying, Hsia, Te-Chun, Su, Wu-Chou, Wu, Shang-Yin, Wang, Chin-Chou, Lee, Kang-Yun, Lin, Sheng-Hao, Lin, Chih-Bin, Lee, Jih-Hsiang, Huang, Chun-Yao, Ahmed, Samreen, Newsom-Davis, Thomas, Baijal, Shobhit, Brock, Juliet, Zaki, Kam, Shamash, Jonathan, Papadatos-Pastos, Dionysis, Jain, Pooja, Jane Mackean, Melanie, Kendall, Stephan DiSean, Anderson, Ian, Costin, Dan, Hall, Richard, Campbell, Nicholas, Khan, Saad, Dowell, Jonathan, Mashru, Sandeep, Menon, Smitha, Raza, Ahmad, Ge, Li, Riely, Gregory J., Seetharamu, Nagashree, Stampleman, Laura, Subramanian, Janakiraman, Wender, Donald B., Natale, Ronald B., Zhu, Viola, Ignatius Ou, Sai-Hong, Sanborn, Rachel, and Evangelist, Makenzi C.

Published
2024
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13. Immersive virtual reality for interdisciplinary trauma management – initial evaluation of a training tool prototype

Author

Laura Isabel Hanke, Lukas Vradelis, Christian Boedecker, Jan Griesinger, Tim Demare, Nicola Raphaele Lindemann, Florentine Huettl, Vuthea Chheang, Patrick Saalfeld, Nicolas Wachter, Jochen Wollstädter, Marike Spranz, Hauke Lang, Christian Hansen, and Tobias Huber

Subjects
Virtual reality, Advanced trauma life support, Training, Interdisciplinary training, Immersive virtual reality training, Medical education, Special aspects of education, LC8-6691, Medicine
Abstract

Abstract Introduction Emergency care of critically ill patients in the trauma room is an integral part of interdisciplinary work in hospitals. Live threatening injuries require swift diagnosis, prioritization, and treatment; thus, different medical specialties need to work together closely for optimal patient care. Training is essential to facilitate smooth performance. This study presents a training tool for familiarization with trauma room algorithms in immersive virtual reality (VR), and a first qualitative assessment. Materials and methods An interdisciplinary team conceptualized two scenarios and filmed these in the trauma room of the University Medical Center Mainz, Germany in 3D-360°. This video content was used to create an immersive VR experience. Participants of the Department of Anesthesiology were included in the study, questionnaires were obtained and eye movement was recorded. Results 31 volunteers participated in the study, of which 10 (32,2%) had completed specialist training in anesthesiology. Participants reported a high rate of immersion (immersion(mean) = 6 out of 7) and low Visually Induced Motion Sickness (VIMS(mean) = 1,74 out of 20). Participants agreed that VR is a useful tool for medical education (mean = 1,26; 1 very useful, 7 not useful at all). Residents felt significantly more secure in the matter after training (p

Published
2024
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15. Amivantamab Plus Lazertinib in Patients With EGFR-Mutant NSCLC After Progression on Osimertinib and Platinum-Based Chemotherapy: Results From CHRYSALIS-2 Cohort A

Author

Besse, Benjamin, Goto, Koichi, Wang, Yongsheng, Lee, Se-Hoon, Marmarelis, Melina E., Ohe, Yuichiro, Bernabe Caro, Reyes, Kim, Dong-Wan, Lee, Jong-Seok, Cousin, Sophie, Ichihara, Eiki, Li, Yongsheng, Paz-Ares, Luis, Ono, Akira, Sanborn, Rachel E., Watanabe, Naohiro, de Miguel, Maria Jose, Helissey, Carole, Shu, Catherine A., Spira, Alexander I., Tomasini, Pascale, Yang, James Chih-Hsin, Zhang, Yiping, Felip, Enriqueta, Griesinger, Frank, Waqar, Saiama N., Calles, Antonio, Neal, Joel W., Baik, Christina S., Jänne, Pasi A., Shreeve, S. Martin, Curtin, Joshua C., Patel, Bharvin, Gormley, Michael, Lyu, Xuesong, Chen, Jun, Chu, Pei-Ling, Mahoney, Janine, Trani, Leonardo, Bauml, Joshua M., Thayu, Meena, Knoblauch, Roland E., and Cho, Byoung Chul

Published
2025
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16. Small cell transformation in EGFR-mutated non-small cell lung cancer: DLL3 expression and efficacy of immune checkpoint inhibitors or tyrosine kinase inhibitors combined with chemotherapy

Author

Saalfeld, Felix Carl, Möller, Johanna, Christopoulos, Petros, Wenzel, Carina, Rasokat, Anna, Wang, Xuejun Alice, Vathiotis, Ioannis, König, David, Illini, Oliver, Grohé, Christian, Wiesweg, Marcel, Wesseler, Claas, Schubart, Christoph, Pelusi, Natalie, Rohde, Gernot, Overbeck, Tobias R., Kirfel, Jutta, Alt, Jürgen, Kauffmann-Guerrero, Diego, Griesinger, Frank, Kulhavy, Jonas, Allgäuer, Michael, Klimova, Anna, Schütz, Maret, Aust, Daniela E., Hochmair, Maximilian J., Rothschild, Sacha I., Syrigos, Konstantinos N., Veluswamy, Rajwanth, Michels, Sebastian, Stenzinger, Albrecht, Jöhrens, Korinna, and Wermke, Martin

Published
2024
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18. Checkpoint Inhibitor Monotherapy in Potentially Trial-Eligible or Trial-Ineligible Patients With Metastatic NSCLC in the German Prospective CRISP Registry Real-World Cohort (AIO-TRK-0315)

Author

Frank Griesinger, MD, PhD, Wilfried E.E. Eberhardt, MD, PhD, Wolfgang M. Brueckl, MD, PhD, Horst-Dieter Hummel, MD, PhD, Bastian Jaeschke, MD, Jens Kern, MD, Claas Wesseler, MD, Martina Jänicke, PdD, Annette Fleitz, PhD, Stefan Zacharias, PhD, Annette Hipper, PhD, Annika Groth, MD, PhD, Wilko Weichert, MD, PhD, Steffen Dörfel, Volker Petersen, MD, Jan Schröder, MD, Jochen Wilke, MD, Martin Sebastian, MD, Michael Thomas, MD, PhD, Juliana Ababei, Jürgen Alt, Andreas Ammon, Jürgen Anhuf, Ivo Azeh, Stefan Bauer, Dirk Behringer, Winfried Berger, Christiane Bernhardt, Mathias Bertram, Michael Boesche, Sabine Bohnet, Harald-Robert Bruch, Wolfgang Brückl, Ulrike Burkhard-Meier, Petros Christopoulos, Klaus-Ulrich Däßler, Maike de Wit, Tobias Dechow, Reinhard Depenbusch, Lutz Dietze, Markus Dommach, Wilfried Eberhardt, Corinna Elender, Wolfgang Elsel, Till-Oliver Emde, Martin Faehling, Thomas Fietz, Jürgen R. Fischer, Dimitri Flieger, Anke Freidt, Werner Freier, Christian Frenzel, Florian Fuchs, Roswitha Fuchs, Tobias Gaska, Wolfgang Gleiber, Christian Grah, Frank Griesinger, Christian Grohé, Matthias Groschek, Björn Güldenzoph, Andreas Günther, Siegfried Haas, Matthias Hackenthal, Volker Hagen, Lars Hahn, Verena Hannig Carla, Richard Hansen, Hanns-Detlev Harich, Monika Heilmann, Kathrin Heinrich, Christiane Hering-Schubert, Jörg Heßling, Petra Hoffknecht, Patricia Hortig, Gerdt Hübner, Horst-Dieter Hummel, Ulrich Hutzschenreuter, Thomas Illmer, Georg Innig, Bastian Jaeschke, Christian Junghanß, Ulrich Kaiser, Haytham Kamal, Kato Kambartel, Jens Kern, Martin Kimmich, Dorothea Kingreen, Heinz Kirchen, Martine Klausmann, Ortwin Klein, Konrad Kokowski, Wolfgang Körber, Cornelius Kortsik, Dirk Koschel, Benoit Krämer, Beate Krammer-Steiner, Eckart Laack, Christof Lamberti, Rumo David Leistner, Christoph Losem, Andreas Lück, Christoph Maintz, Kerstin Martin, Dirk Medgenberg, Martin Metzenmacher, Christian Meyer zum Büschenfelde, Philipp Meyn, Enno Moorahrend, Annette Müller, Lothar Müller, Michael Neise, Holger Nückel, Arnd Nusch, Tobias Overbeck, Henning Pelz, Volker Petersen, Bettina Peuser, Margarete Plath, Winfried J. Randerath, Jacqueline Rauh, Martin Reck, Dietmar Reichert, Niels Reinmuth, Marcel Reiser, Roland Repp, Daniel Reschke, Achim Rittmeyer, Yolanda Rodemer, Sandra Sackmann, Parvis Sadjadian, Reiner Sandner, Annette Sauer, Harald Schäfer, Christoph Schaudt, Rudolf Schlag, Burkhard Schmidt, Stephan Schmitz, Jan Schröder, Michael Schroeder, Mathias Schulze, Christian Schumann, Wolfgang Schütte, Martin Schwaiblmair, Florian Schwindt Peter, Martin Sebastian, Bernd Seese, Gernot Seipelt, Thomas Sorgenfrei, Johannes Steiff, Heike Steiniger, Tanja Trarbach, Amanda Tufman, Jens Uhlig, Ursula Vehling-Kaiser, Eyck von der Heyde, Ulla von Verschuer, Cornelius Waller, Thomas Wehler, Georg Weißenborn, Florian Weißinger, Martin Wermke, Claas Wesseler, Jörg Wiegand, Stefan Wilhelm, Jochen Wilke, Mark-Oliver Zahn, Matthias Zaiss, and Matthias Zeth

Subjects
Non–small cell lung carcinoma, Prospective studies, Immune checkpoint inhibitors, Pembrolizumab, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Introduction: Patients with metastatic NSCLC (mNSCLC) treated with immune checkpoint inhibitors in clinical practice may often not meet the strict inclusion criteria of clinical trials. Our aim was to assess the trial eligibility of patients with mNSCLC treated with pembrolizumab monotherapy in real-world and to compare the outcome of “trial-ineligible” and “potentially trial-eligible” patients. Methods: Data from the prospective, clinical research platform CRISP were used to compare patient characteristics, treatment, and outcome of patients with programmed cell death-ligand 1 tumor proportion score greater than or equal to 50% tumors treated with pembrolizumab monotherapy who are deemed either “potentially trial-eligible” or “trial-ineligible” according to inclusion and exclusion criteria of the registrational studies (KEYNOTE-024 and -042). Results: Of 746 patients included, 343 patients (46.0%) were classified as “trial-ineligible” and had significantly worse outcomes compared with “potentially trial-eligible” patients (n = 403, 54.0%): median progression-free survival: 6.2 (95% confidence interval [CI]: 5.2–8.4) versus 10.3 (95% CI: 8.4–13.8) months, hazard ratio (trial-ineligible versus potentially trial-eligible) of 1.43 (95% CI: 1.19–1.72), p less than 0.001; median overall survival: 15.9 (95% CI: 11.4–20.3) versus 25.3 (95% CI: 19.8–30.4) months, hazard ratio of 1.36 (95% CI: 1.10–1.67), p equals 0.004. Conclusions: Our data reveal that a considerable proportion of patients with mNSCLC are not eligible to participate in a clinical trial and were found to have worse outcomes than potentially trial-eligible patients, whose outcomes were comparable with those obtained from pivotal clinical trials. This is of substantial clinical relevance for physicians discussing outcomes to be expected with their patients and stresses the need for real-world effectiveness analyses.

Published
2024
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19. Adressen

Author

Gembruch, Ulrich, primary, Hancke, Katharina, additional, Felberbaum, Ricardo Enrique, additional, Kainer, Franz, additional, Kolberg, Hans-Christian, additional, Ortmann, Olaf, additional, Janni, Wolfgang, additional, Anwander, Maria-Rita, additional, Balogh, Balint, additional, Bals-Pratsch, Monika, additional, Bauerschlag, Dirk, additional, Bittner, Ann-Kathrin, additional, Botez, Ciprian, additional, Brössner, Anke, additional, Engels, Alexander, additional, Gembruch, Ulrich, additional, Grebe, Sandra, additional, Griesinger, Georg, additional, Heilmann, Thorsten, additional, Hetterich, Madeleine, additional, Hollatz-Galuschki, Elsa, additional, Hutter, Stefan, additional, Ignatov, Atanas, additional, Inwald, Elisabeth C., additional, Juhasz-Böss, Ingolf, additional, Kellermann, Pia, additional, Knabl, Julia, additional, Kolberg-Liedtke, Cornelia, additional, Kouskouti, Christina, additional, Krapp, Martin, additional, Kaisenberg, Heidi Kühling von, additional, Petrich, Julia, additional, Puhl, Alexander G., additional, Rauber, Susanne, additional, Schultze-Mosgau, Askan, additional, Sczesny, Robert, additional, Seegers, Nora, additional, Seitz, Stephan, additional, Steinhoff-Kellner, Alina, additional, van der Ven, Katrin, additional, van Mackelenbergh, Marion Tina, additional, Kaisenberg, Constantin von, additional, Vu, Thu Huong, additional, Walter, Adeline, additional, Weber, Eva, additional, and Wetzig, Sarah, additional

Published
2024
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20. Molecular Diffusivity of Click Reaction Components: The Diffusion Enhancement Question

Author

Rezaei-Ghaleh, Nasrollah, Agudo-Canalejo, Jaime, Griesinger, Christian, and Golestanian, Ramin

Subjects
Physics - Chemical Physics
Abstract

Micrometer-sized objects are widely known to exhibit chemically-driven motility in systems away from equilibrium. Experimental observation of reaction-induced motility or enhancement in diffusivity at the much shorter length scale of small molecules is however still a matter of debate. Here, we investigate the molecular diffusivity of reactants, catalyst and product of a model reaction, the copper-catalyzed azide-alkyne cycloaddition click reaction, and develop new NMR diffusion approaches that allow the probing of reaction-induced diffusion enhancement in nano-sized molecular systems with higher precision than the state of the art. Following two different approaches that enable the accounting of time-dependent concentration changes during NMR experiments, we closely monitored the diffusion coefficient of reaction components during the reaction. The reaction components showed distinct changes in the diffusivity: while the two reactants underwent a time-dependent decrease in their diffusivity, the diffusion coefficient of the product gradually increased and the catalyst showed only slight diffusion enhancement within the range expected for reaction-induced sample heating. The decrease in diffusion coefficient of the alkyne, one of the two reactants of click reaction, was not reproduced during its copper coordination when the second reactant, azide, was absent. Our results do not support the catalysis-induced diffusion enhancement of the components of click reaction and, instead, point to the role of a relatively large intermediate species within the reaction cycle with diffusivity lower than both the reactants and product molecule., Comment: 14 pages and 10 figures (including main manuscript, TOC figure and supporting information)

Published
2021
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24. 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

Hilbrandt, Moritz, Süptitz, Juliane, Grah, Christian, Velthaus, Janna-Lisa, Kopp, Hans-Georg, Schmidt, Bernd, Horter, Susanne, Keymel, Stefanie, Aydilek, Enver, Tritchkova, Guergana, Raspe, Matthias, Papić, Dražen, Florian, Stefan, Horst, David, Wild, Peter J., Thomas, Michael, Grohé, Christian, Bleckmann, Annalen, Wermke, Martin, Hummel, Horst-Dieter, Stratmann, Jan, Schütte, Wolfgang, 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, Stenzinger, Albrecht, Stephan-Falkenau, Susann, Trautmann, Marcel, Lassmann, Silke, Tiemann, Markus, Klauschen, Frederick, Sebastian, Martin, Griesinger, Frank, Wolf, Jürgen, Loges, Sonja, and Frost, Nikolaj

Published
2024
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25. Sotorasib in KRAS G12C-mutated non-small cell lung cancer: A multicenter real-world experience from the compassionate use program in Germany

Author

Stratmann, Jan A., Althoff, Friederike C., Doebel, Paula, Rauh, Jacqueline, Trummer, Arne, Hünerlitürkoglu, Ali Nuri, Frost, Nikolaj, Yildirim, Hüsameddin, Christopoulos, Petros, Burkhard, Oswald, Büschenfelde, Christian Meyer zum, Becker von Rose, Aaron, Alt, Jürgen, Aries, Sven P., Webendörfer, Maximilian, Kaldune, Stefan, Uhlenbruch, Mark, Tritchkova, Guergana, Waller, Cornelius F., Rittmeyer, Achim, Hoffknecht, Petra, Braess, Jan, Kopp, Hans-Georg, Grohé, Christian, Schäfer, Monica, Schumann, Christian, Griesinger, Frank, Kuon, Jonas, Sebastian, Martin, and Reinmuth, Niels

Published
2024
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26. Integration of single-nuclei RNA-sequencing, spatial transcriptomics and histochemistry defines the complex microenvironment of NF1-associated plexiform neurofibromas

Author

Vladimir Amani, Kent A. Riemondy, Rui Fu, Andrea M. Griesinger, Enrique Grimaldo, Graziella Ribeiro De Sousa, Ahmed Gilani, Molly Hemenway, Nicholas K. Foreman, Andrew M. Donson, and Nicholas Willard

Subjects
Neurology. Diseases of the nervous system, RC346-429
Abstract

Abstract Plexiform neurofibroma (PN) is a leading cause of morbidity in children with the genetic condition Neurofibromatosis Type 1 (NF1), often disfiguring or threatening vital structures. During formation of PN, a complex tumor microenvironment (TME) develops, with recruitment of neoplastic and non-neoplastic cell types being critical for growth and progression. Due to the cohesive cellularity of PN, single-cell RNA-sequencing is difficult and may result in a loss of detection of critical cellular subpopulations. To bypass this barrier, we performed single-nuclei RNA-sequencing (snRNA-seq) on 8 frozen PN samples, and integrated this with spatial transcriptomics (ST) in 4 PN samples and immunohistochemistry to provide morphological context to transcriptomic data. SnRNA-seq analysis definitively charted the heterogeneous cellular subpopulations in the PN TME, with the predominant fraction being fibroblast subtypes. PN showed a remarkable amount of inter-sample homogeneity regarding cellular subpopulation proportions despite being resected from a variety of anatomical locations. ST analysis identified distinct cellular subpopulations which were annotated using snRNA-seq data and correlated with histological features. Schwann cell/fibroblast interactions were identified by receptor/ligand interaction analysis demonstrating a high probability of Neurexin 1/Neuroligin 1 (NRXN1/NLGN1) receptor-ligand cross-talk predicted between fibroblasts and non-myelinated Schwann cells (NM-SC) and subtypes, respectively. We observed aberrant expression of NRXN1 and NLGN1 in our PN snRNA-seq data compared to a normal mouse sciatic nerve single-cell RNA-seq dataset. This pathway has never been described in PN and may indicate a clear and direct communication pathway between putative NM-SC cells of origin and surrounding fibroblasts, potentially driving disease progression. SnRNA-seq integrated with spatial transcriptomics advances our understanding of the complex cellular heterogeneity of PN TME and identify potential novel communication pathways that may drive disease progression, a finding that could provide translational therapy options for patients with these devastating tumors of childhood and early adulthood.

Published
2023
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27. Targeting integrated epigenetic and metabolic pathways in lethal childhood PFA ependymomas

Author

Panwalkar, Pooja, Tamrazi, Benita, Dang, Derek, Chung, Chan, Sweha, Stefan, Natarajan, Siva Kumar, Pun, Matthew, Bayliss, Jill, Ogrodzinski, Martin P, Pratt, Drew, Mullan, Brendan, Hawes, Debra, Yang, Fusheng, Lu, Chao, Sabari, Benjamin R, Achreja, Abhinav, Heon, Jin, Animasahun, Olamide, Cieslik, Marcin, Dunham, Christopher, Yip, Stephen, Hukin, Juliette, Phillips, Joanna J, Bornhorst, Miriam, Griesinger, Andrea M, Donson, Andrew M, Foreman, Nicholas K, Garton, Hugh JL, Heth, Jason, Muraszko, Karin, Nazarian, Javad, Koschmann, Carl, Jiang, Li, Filbin, Mariella G, Nagrath, Deepak, Kool, Marcel, Korshunov, Andrey, Pfister, Stefan M, Gilbertson, Richard J, Allis, C David, Chinnaiyan, Arul M, Lunt, Sophia Y, Blüml, Stefan, Judkins, Alexander R, and Venneti, Sriram

Subjects
Medical Biotechnology, Biomedical and Clinical Sciences, Orphan Drug, Brain Disorders, Neurosciences, Human Genome, Rare Diseases, Biotechnology, Cancer, Genetics, Pediatric Cancer, Brain Cancer, Pediatric, 2.1 Biological and endogenous factors, Animals, Child, Ependymoma, Epigenesis, Genetic, Epigenomics, Histones, Humans, Metabolic Networks and Pathways, Mice, Biological Sciences, Medical and Health Sciences, Medical biotechnology, Biomedical engineering
Abstract

Childhood posterior fossa group A ependymomas (PFAs) have limited treatment options and bear dismal prognoses compared to group B ependymomas (PFBs). PFAs overexpress the oncohistone-like protein EZHIP (enhancer of Zeste homologs inhibitory protein), causing global reduction of repressive histone H3 lysine 27 trimethylation (H3K27me3), similar to the oncohistone H3K27M. Integrated metabolic analyses in patient-derived cells and tumors, single-cell RNA sequencing of tumors, and noninvasive metabolic imaging in patients demonstrated enhanced glycolysis and tricarboxylic acid (TCA) cycle metabolism in PFAs. Furthermore, high glycolytic gene expression in PFAs was associated with a poor outcome. PFAs demonstrated high EZHIP expression associated with poor prognosis and elevated activating mark histone H3 lysine 27 acetylation (H3K27ac). Genomic H3K27ac was enriched in PFAs at key glycolytic and TCA cycle–related genes including hexokinase-2 and pyruvate dehydrogenase. Similarly, mouse neuronal stem cells (NSCs) expressing wild-type EZHIP (EZHIP-WT) versus catalytically attenuated EZHIP-M406K demonstrated H3K27ac enrichment at hexokinase-2 and pyruvate dehydrogenase, accompanied by enhanced glycolysis and TCA cycle metabolism. AMPKα-2, a key component of the metabolic regulator AMP-activated protein kinase (AMPK), also showed H3K27ac enrichment in PFAs and EZHIP-WT NSCs. The AMPK activator metformin lowered EZHIP protein concentrations, increased H3K27me3, suppressed TCA cycle metabolism, and showed therapeutic efficacy in vitro and in vivo in patient-derived PFA xenografts in mice. Our data indicate that PFAs and EZHIP-WT–expressing NSCs are characterized by enhanced glycolysis and TCA cycle metabolism. Repurposing the antidiabetic drug metformin lowered pathogenic EZHIP, increased H3K27me3, and suppressed tumor growth, suggesting that targeting integrated metabolic/epigenetic pathways is a potential therapeutic strategy for treating childhood ependymomas.

Published
2021

28. Author Correction: Chemoselective umpolung of thiols to episulfoniums for cysteine bioconjugation

Author

Hartmann, Philipp, Bohdan, Kostiantyn, Hommrich, Moritz, Juliá, Fabio, Vogelsang, Lara, Eirich, Jürgen, Zangl, Rene, Farès, Christophe, Jacobs, Julia Beatrice, Mukhopadhyay, Dwaipayan, Mengeler, Johanna Marie, Vetere, Alessandro, Sterling, Marie Sophie, Hinrichs, Heike, Becker, Stefan, Morgner, Nina, Schrader, Wolfgang, Finkemeier, Iris, Dietz, Karl-Josef, Griesinger, Christian, and Ritter, Tobias

Published
2024
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31. An Adjusted Treatment Comparison Comparing Amivantamab Versus Real-World Clinical Practice in Europe and the United States for Patients with Advanced Non-Small Cell Lung Cancer with Activating Epidermal Growth Factor Receptor Exon 20 Insertion Mutations

Author

Chouaid, Christos, Bosquet, Lise, Girard, Nicolas, Kron, Anna, Scheffler, Matthias, Griesinger, Frank, Sebastian, Martin, Trigo, Jose, Viteri, Santiago, Knott, Craig, Rodrigues, Bernardo, Rahhali, Nora, Cabrieto, Jedelyn, Diels, Joris, Perualila, Nolen J., Schioppa, Claudio A., Sermon, Jan, Toueg, Raphael, Erdmann, Nicole, Mielke, Janka, Nematian-Samani, Mehregan, Martin-Fernandez, Cristina, Pfaira, Innocent, Li, Tracy, Mahadevia, Parthiv, and Wolf, Jürgen

Published
2023
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36. USING INSTRUCTIONAL ROUNDS TO GUIDE PD

Author

Griesinger, Matt

Subjects
Professional development -- Study and teaching, Teachers -- Training, Teacher centers -- Forecasts and trends, Career education -- Forecasts and trends, Leadership -- Study and teaching, Market trend/market analysis, Education
Abstract

NORTHWEST EDUCATION SERVICES CAREER TECH SERVES 1,200 STUDENTS FROM 24 HIGH SCHOOLS in northern Michigan. Across 21 programs ranging from construction trades to creative writing, and engineering to graphic arts, [...]

Published
2023

37. The 3D structure of lipidic fibrils of α-synuclein

Author

Benedikt Frieg, Leif Antonschmidt, Christian Dienemann, James A. Geraets, Eszter E. Najbauer, Dirk Matthes, Bert L. de Groot, Loren B. Andreas, Stefan Becker, Christian Griesinger, and Gunnar F. Schröder

Subjects
Science
Abstract

Interactions between α-synuclein fibrils and lipids have been associated with the development of Parkinson’s disease. This cryo-EM study reveals structural details of these interactions and suggests a mechanism for fibril-induced lipid extraction.

Published
2022
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38. Evaluation of the Prognostic Impact of SP263-Evaluated PD-L1 Expression in Patients with Stage III Non-Small Cell Lung Cancer (NSLC) Treated with Radio-Chemotherapy

Author

Jan Nicolai Wagner, Julia Roeper, Lukas Heukamp, Markus Falk, Kay Willborn, and Frank Griesinger

Subjects
local advanced NSCLC, stage III, PD-L1, radio-chemotherapy, lung cancer, Biology (General), QH301-705.5
Abstract

Background: The PACIFIC study showed that after radio-chemotherapy, patients with NSCLC derived a benefit in PFS and OS when treated with durvalumab. This effect was limited to patients with a PD-L1 expression of >1%, partly because the outcome in the observational control arm was surprisingly favorable. Thus, it could be speculated that a lack of PD-L1 expression confers a favorable outcome for patients with stage III NSCLC. Methods: Clinical data, PD-L1 expression, predictive blood markers, and the outcomes of 99 homogeneously treated patients with stage III NSCLC were retrospectively captured. Statistical analyses using the log rank test were performed. Results: The median OS of patients with an expression of PD-L1 < 1% was 20 months (CI 10.5–29.5) and the median OS of patients with an expression of PD-L1 ≥ 1% was 28 months (CI 16.5–39.2) (p = 0.734). The median PFS of patients with an expression of PD-L1 < 1% was 9 months (CI 6.3–11.6) and the median PFS of patients with an expression of PD-L1 ≥ 1% was 12 months (CI 9.8–14.2) (p = 0.112). Conclusions: The assumption that the lack of PD-L1 expression represents a favorable prognostic factor after radio-chemotherapy vs. PD-L1 expression > 1% was not confirmed.

Published
2024
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42. The clinical drug candidate anle138b binds in a cavity of lipidic α-synuclein fibrils

Author

Leif Antonschmidt, Dirk Matthes, Rıza Dervişoğlu, Benedikt Frieg, Christian Dienemann, Andrei Leonov, Evgeny Nimerovsky, Vrinda Sant, Sergey Ryazanov, Armin Giese, Gunnar F. Schröder, Stefan Becker, Bert L. de Groot, Christian Griesinger, and Loren B. Andreas

Subjects
Science
Abstract

Understanding how small molecules bind to pathological aggregates is of importance for therapeutic and diagnostic development in diseases such as Parkinson’s Disease. Here, the authors reveal a binding site of anle138b to lipid-induced α-synuclein fibrils.

Published
2022
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43. Acquired G2032R Resistance Mutation in ROS1 to Lorlatinib Therapy Detected with Liquid Biopsy

Author

Balázs Jóri, Markus Falk, Iris Hövel, Peggy Weist, Markus Tiemann, Lukas C. Heukamp, and Frank Griesinger

Subjects
NSCLC, lorlatinib, ROS1, resistance mutation, liquid biopsy, G2032R, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Lorlatinib, a third-generation anaplastic lymphoma kinase (ALK)/receptor tyrosine kinase inhibitor (ROS1), demonstrated efficacy in ROS1 positive (ROS1+) non-small cell lung cancer (NSCLC), although approval is currently limited to the treatment of ALK+ patients. However, lorlatinib-induced resistance mechanisms, and its efficacy against the resistance mutation G2032R in ROS1, respectively, have not yet been fully understood. Furthermore, concomitant tumor suppressor gene p53 (TP53) mutations occur in driver alteration positive NSCLC, but their prognostic contribution in the context of ROS1 inhibition remains unclear. Here we report a ROS1+ NSCLC patient who developed an on target G2032R resistance mutation during second-line lorlatinib treatment, indicating the lack of activity of lorlatinib against ROS1 G2032R. The resistance mutation was detected in plasma-derived ctDNA, signifying the clinical utility of liquid biopsies.

Published
2022
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44. Efficacy and Safety of Brigatinib Compared With Crizotinib in Asian vs. Non-Asian Patients With Locally Advanced or Metastatic ALK–Inhibitor-Naive ALK+ Non–Small Cell Lung Cancer: Final Results From the Phase III ALTA-1L Study

Author

Ahn, Myung J., Kim, Hye R., Yang, James C.H., Han, Ji-Yu, Li, Jacky Yu-Chung., Hochmair, Maximilian J., Chang, Gee-Chen, Delmonte, Angelo, Lee, Ki H., Campelo, Rosario G., Gridelli, Cesare, Spira, Alexander I., Califano, Raffaele, Griesinger, Frank, Ghosh, Sharmistha, Felip, Enriqueta, Kim, Dong-Wan, Liu, Yuyin, Zhang, Pingkuan, Popat, Sanjay, and Camidge, D. Ross

Published
2022
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45. Safety and efficacy of pralsetinib in RET fusion–positive non-small-cell lung cancer including as first-line therapy: update from the ARROW trial

Author

Griesinger, F., Curigliano, G., Thomas, M., Subbiah, V., Baik, C.S., Tan, D.S.W., Lee, D.H., Misch, D., Garralda, E., Kim, D.-W., van der Wekken, A.J., Gainor, J.F., Paz-Ares, L., Liu, S.V., Kalemkerian, G.P., Houvras, Y., Bowles, D.W., Mansfield, A.S., Lin, J.J., Smoljanovic, V., Rahman, A., Kong, S., Zalutskaya, A., Louie-Gao, M., Boral, A.L., and Mazières, J.

Published
2022
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46. Radiation and Dose-densification of R-CHOP in Primary Mediastinal B-cell Lymphoma: Subgroup Analysis of the UNFOLDER Trial

Author

Gerhard Held, Lorenz Thurner, Viola Poeschel, German Ott, Christian Schmidt, Konstantinos Christofyllakis, Andreas Viardot, Peter Borchmann, Walburga Engel-Riedel, Norbert Frickhofen, Maike Nickelsen, Ofer Shpilberg, Mathias Witzens-Harig, Frank Griesinger, Beate Krammer-Steiner, Andreas Neubauer, Peter de Nully Brown, Massimo Federico, Bertram Glass, Norbert Schmitz, Gerald Wulf, Lorenz Truemper, Moritz Bewarder, Niels Murawski, Stephan Stilgenbauer, Andreas Rosenwald, Bettina Altmann, Marianne Engelhard, Heinz Schmidberger, Jochen Fleckenstein, Christian Berdel, Markus Loeffler, Marita Ziepert, and on behalf of the German Lymphoma Alliance (GLA)

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

UNFOLDER (NCT00278408, EUDRACT 2005-005218-19) is a phase-3 trial in patients with aggressive B-cell lymphoma and intermediate prognosis, including primary mediastinal B-cell lymphoma (PMBCL). In a 2 × 2 factorial design, patients were randomized to 6× R-CHOP-14 or R-CHOP-21 (rituximab, cyclophosphamide, doxorubicin, vincristine, and prediso(lo)ne) and to consolidation radiotherapy to extralymphatic/bulky disease or observation. Response was assessed according to the standardized criteria from 1999, which did not include F-18 fluordesoxyglucose positron emission tomography/computed tomography (FDG-PET) scans. Primary end point was event-free survival (EFS). A subgroup of 131 patients with PMBCLs was included (median age, 34 y; 54% female, 79% elevated lactate dehydrogenase (LDH), 20% LDH >2× upper limit of normal [ULN], and 24% extralymphatic involvement). Eighty-two (R-CHOP-21: 43 and R-CHOP-14: 39) patients were assigned to radiotherapy and 49 (R-CHOP-21: 27, R-CHOP-14: 22) to observation. The 3-year EFS was superior in radiotherapy arm (94% [95% confidence interval (CI), 89-99] versus 78% [95% CI, 66-89]; P = 0.0069), due to a lower rate of partial responses (PRs) (2% versus 10%). PR triggered additional treatment, mostly radiotherapy (n = 5; PR: 4; complete response/unconfirmed complete response: 1). No significant differences were observed in progression-free survival (PFS) (95% [95% CI, 90-100] versus 90% [95% CI, 81-98]; P = 0.25) nor in overall survival (OS) (98% [95% CI, 94-100] versus 96% [95% CI, 90-100]; P = 0.64). Comparing R-CHOP-14 and R-CHOP-21, EFS, PFS, and OS were not different. A prognostic marker for adverse outcome was elevated LDH >2× ULN (EFS: P = 0.016; PFS: P = 0.0049; OS: P = 0.0014). With the limitation of a pre-PET-era trial, the results suggest a benefit of radiotherapy only for patients responding to R-CHOP with PR. PMBCL treated with R-CHOP have a favorable prognosis with a 3-year OS of 97%.

Published
2023
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47. Radiation and Dose-densification of R-CHOP in Aggressive B-cell Lymphoma With Intermediate Prognosis: The UNFOLDER Study

Author

Lorenz Thurner, Marita Ziepert, Christian Berdel, Christian Schmidt, Peter Borchmann, Dominic Kaddu-Mulindwa, Andreas Viardot, Mathias Witzens-Harig, Judith Dierlamm, Mathias Haenel, Bernd Metzner, Gerald Wulf, Eva Lengfelder, Ulrich B. Keller, Norbert Frickhofen, Maike Nickelsen, Tobias Gaska, Frank Griesinger, Rolf Mahlberg, Reinhard Marks, Ofer Shpilberg, Hans-Walter Lindemann, Martin Soekler, Ludwig Fischer von Weikersthal, Michael Kiehl, Eva Roemer, Martin Bentz, Beate Krammer-Steiner, Ralf Trappe, Peter de Nully Brown, Massimo Federico, Francesco Merli, Marianne Engelhard, Bertram Glass, Norbert Schmitz, Lorenz Truemper, Moritz Bewarder, Frank Hartmann, Niels Murawski, Stephan Stilgenbauer, Andreas Rosenwald, Bettina Altmann, Heinz Schmidberger, Jochen Fleckenstein, Markus Loeffler, Viola Poeschel, Gerhard Held, and on behalf of German Lymphoma Alliance (GLA)

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

UNFOLDER (Unfavorable Young Low-Risk Densification of R-Chemo Regimens) is an international phase-3 trial in patients 18–60 years with aggressive B-cell lymphoma and intermediate prognosis defined by age-adjusted International Prognostic Index (aaIPI) of 0 and bulky disease (≥7.5 cm) or aaIPI of 1. In a 2 × 2 factorial design patients were randomized to 6× R-CHOP-14 or 6× R-CHOP-21 (rituximab, cyclophosphamide, doxorubicin, vincristine, and prediso[lo]ne) and to consolidation radiotherapy to extralymphatic and bulky disease or observation. Response was assessed according to the standardized response criteria published in 1999, not including F-18 fluordesoxyglucose positron emission tomography/computed tomography (FDG-PET). Primary endpoint was event-free survival (EFS). A total of 695 of 700 patients were eligible for the intention-to-treat analysis. Totally 467 patients qualified for radiotherapy of whom 305 patients were randomized to receive radiotherapy (R-CHOP-21: 155; R-CHOP-14: 150) and 162 to observation (R-CHOP-21: 81, R-CHOP-14: 81). Two hundred twenty-eight patients not qualifying for radiotherapy were randomized for R-CHOP-14 versus R-CHOP-21. After a median observation of 66 months 3-year EFS was superior in the radiotherapy-arm versus observation-arm (84% versus 68%; P = 0.0012), due to a lower rate of partial responses (PR) (2% versus 11%). PR often triggered additional treatment, mostly radiotherapy. No significant difference was observed in progression-free survival (PFS) (89% versus 81%; P = 0.22) and overall survival (OS) (93% versus 93%; P = 0.51). Comparing R-CHOP-14 and R-CHOP-21 EFS, PFS and OS were not different. Patients randomized to radiotherapy had a superior EFS, largely due to a lower PR rate requiring less additional treatment (NCT00278408, EUDRACT 2005-005218-19).

Published
2023
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48. Impact of immune checkpoint inhibitors on the management of locally advanced or metastatic non-small cell lung cancer in real-life practice in patients initiating treatment between 2015 and 2018 in France and Germany

Author

Griesinger, Frank, Pérol, Maurice, Girard, Nicolas, Durand-Zaleski, Isabelle, Zacharias, Stefan, Bosquet, Lise, Jänicke, Martina, Quantin, Xavier, Groth, Annika, Fleitz, Annette, Calleja, Alan, Patel, Sonya, Lacoin, Laure, Daumont, Melinda J., Penrod, John R., Carroll, Robert, Waldenberger, Daniela, Reynaud, Dorothée, Thomas, Michael, and Chouaid, Christos

Published
2022
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49. Recurrence patterns and impact of brain metastases in synchronous single organ oligometastatic lung cancer following local ablative treatment – A multicenter analysis

Author

Frost, Nikolaj, Roeper, Julia, Velthaus, Janna-Lisa, Raspe, Matthias, Olive, Elisabeth, Schmittel, Alexander, Schmidt, Bernd, Wasilewski, David, Onken, Julia, Lüders, Heike, Witzenrath, Martin, Senger, Carolin, Böhmer, Dirk, Loges, Sonja, Griesinger, Frank, Modest, Dominik P., and Grohé, Christian

Published
2022
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