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3. Clinicopathologic and molecular characteristics of small-scale ROS1-mutant non-small cell lung cancer (NSCLC) patients

Author

Glaser, Moritz, Rasokat, Anna, Prang, Darinka, Nogova, Lucia, Wömpner, Claudia, Schmitz, Jaqueline, Bitter, Elisabeth, Terjung, Inken, Eisert, Anna, Fischer, Rieke, John, Felix, von Levetzow, Cornelia, Michels, Sebastian, Riedel, Richard, Ruge, Lea, Scharpenseel, Heather, Siebolts, Udo, Merkelbach-Bruse, Sabine, Buettner, Reinhard, Brägelmann, Johannes, Wolf, Jürgen, and Scheffler, Matthias

Published
2023
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4. Resistance to MET inhibition in MET-dependent NSCLC and therapeutic activity after switching from type I to type II MET inhibitors

Author

Riedel, Richard, Fassunke, Jana, Tumbrink, Hannah L., Scheel, Andreas H., Heydt, Carina, Hieggelke, Lena, Scheffler, Matthias, Heimsoeth, Alena, Nogova, Lucia, Michels, Sebastian, Weber, Jan-Phillip, Fischer, Rieke N., Eisert, Anna, Westphal, Theresa, Schaufler, Diana, Siemanowski, Janna, Ihle, Michaela A., Wagener-Ryczek, Svenja, Castiglione, Roberta, Pappesch, Roberto, Rehker, Jan, Jürgens, Jessica, Stoelben, Erich, Bunck, Anne, Kobe, Carsten, Merkelbach-Bruse, Sabine, Sos, Martin L., Büttner, Reinhard, and Wolf, Jürgen

Published
2023
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6. Rebiopsy in advanced non-small cell lung cancer, clinical relevance and prognostic implications

Author

Scheffler, Matthias, Wiesweg, Marcel, Michels, Sebastian, Nogová, Lucia, Kron, Anna, Herold, Thomas, Scheel, Andreas H., Metzenmacher, Martin, Eberhardt, Wilfried E., Reis, Henning, Fassunke, Jana, Darwiche, Kaid, Aigner, Clemens, Schaufler, Diana, Riedel, Richard, Fischer, Rieke, Koleczko, Sophia, Schildhaus, Hans-Ulrich, Merkelbach-Bruse, Sabine, Schmid, Kurt W., Büttner, Reinhard, Wolf, Jürgen, and Schuler, Martin

Published
2022
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7. Somatic rearrangements causing oncogenic ectodomain deletions of FGFR1 in squamous cell lung cancer

Author

Malchers, Florian, Nogova, Lucia, van Attekum, Martijn H.A., Maas, Lukas, Bragelmann, Johannes, Bartenhagen, Christoph, Girard, Luc, Bosco, Graziella, Dahmen, Ilona, Michels, Sebastian, Weeden, Clare E., Scheel, Andreas H., Meder, Lydia, Golfmann, Kristina, Schuldt, Philipp, Siemanowski, Janna, Rehker, Jan, Merkelbach-Bruse, Sabine, Menon, Roopika, Gautschi, Oliver, Heuckmann, Johannes M., Brambilla, Elisabeth, Asselin-Labat, Marie-Liesse, Persigehl, Thorsten, Minna, John D., Walczak, Henning, Ullrich, Roland T., Fischer, Matthias, Reinhardt, Hans Christian, Wolf, Jurgen, Buttner, Reinhard, Peifer, Martin, George, Julie, and Thomas, Roman K.

Subjects
Physiological aspects, Development and progression, Genetic aspects, Health aspects, Lung cancer -- Genetic aspects -- Development and progression, Protein-tyrosine kinase -- Physiological aspects -- Health aspects, Fibroblast growth factors -- Genetic aspects -- Health aspects -- Physiological aspects, Squamous cell carcinoma -- Genetic aspects -- Development and progression, Protein tyrosine kinase -- Physiological aspects -- Health aspects
Abstract

Introduction Squamous cell lung cancer (SQLC) is the second most common lung cancer subtype and among the cancers with the worst prognosis (1). Unfortunately, genetically activated kinase targets that provide [...], The discovery of frequent 8p11-p12 amplifications in squamous cell lung cancer (SQLC) has fueled hopes that FGFR1, located inside this amplicon, might be a therapeutic target. In a clinical trial, only 11% of patients with 8p11 amplification (detected by FISH) responded to FGFR kinase inhibitor treatment. To understand the mechanism of FGFR1 dependency, we performed deep genomic characterization of 52 SQLCs with 8p11-p12 amplification, including 10 tumors obtained from patients who had been treated with FGFR inhibitors. We discovered somatically altered variants of FGFR1 with deletion of exons 1-8 that resulted from intragenic tail-to-tail rearrangements. These ectodomain-deficient FGFR1 variants ([DELTA]EC-FGFR1) were expressed in the affected tumors and were tumorigenic in both in vitro and in vivo models of lung cancer. Mechanistically, breakage-fusion-bridges were the source of 8p11-p12 amplification, resulting from frequent head-to-head and tail-to-tail rearrangements. Generally, tail-to-tail rearrangements within or in close proximity upstream of FGFR1 were associated with FGFR1 dependency. Thus, the genomic events shaping the architecture of the 8p11-p12 amplicon provide a mechanistic explanation for the emergence of FGFR1-driven SQLC. Specifically, we believe that FGFR1 ectodomain-deficient and FGFRI-centered amplifications caused by tail-to-tail rearrangements are a novel somatic genomic event that might be predictive of therapeutically relevant FGFR1 dependency.

Published
2023
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9. Durable Response With Sequential Tyrosine Kinase Inhibitor Treatment in a Patient With ROS1 Fusion–Positive Pancreatic Adenocarcinoma: A Case Report

Author

Reutter, Theresa, Fassunke, Jana, Püsken, Michael, Weber, Jan-Phillip, Binot, Elke, Eisert, Anna, Fischer, Rieke, Nogova, Lucia, Riedel, Richard, Schaufler, Diana, Scharpenseel, Heather, Scheffler, Matthias, Schulz, Holger, Waldschmidt, Dirk‐Thomas, Zander, Thomas, Merkelbach-Bruse, Sabine, Schirmacher, Peter, Büttner, Reinhard, Wolf, Jürgen, and Michels, Sebastian

Published
2023
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10. Genetic Heterogeneity of MET-Aberrant NSCLC and Its Impact on the Outcome of Immunotherapy

Author

Kron, Anna, Scheffler, Matthias, Heydt, Carina, Ruge, Lea, Schaepers, Carsten, Eisert, Anna-Kristina, Merkelbach-Bruse, Sabine, Riedel, Richard, Nogova, Lucia, Fischer, Rieke Nila, Michels, Sebastian, Abdulla, Diana S.Y., Koleczko, Sophia, Fassunke, Jana, Schultheis, Anne M., Kron, Florian, Ueckeroth, Frank, Wessling, Gabriele, Sueptitz, Juliane, Beckers, Frank, Braess, Jan, Panse, Jens, Grohé, Christian, Hamm, Michael, Kabitz, Hans-Joachim, Kambartel, Kato, Kaminsky, Britta, Krueger, Stefan, Schulte, Clemens, Lorenz, Joachim, Lorenzen, Johann, Meister, Wolfram, Meyer, Andreas, Kappes, Jutta, Reinmuth, Niels, Schaaf, Bernhard, Schulte, Wolfgang, Serke, Monika, Buettner, Reinhard, and Wolf, Jürgen

Published
2021
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11. Co-occurrence of targetable mutations in Non-small cell lung cancer (NSCLC) patients harboring MAP2K1 mutations

Author

Scheffler, Matthias, Holzem, Alessandra, Kron, Anna, Nogova, Lucia, Ihle, Michaela A., von Levetzow, Cornelia, Fassunke, Jana, Wömpner, Claudia, Bitter, Elisabeth, Koleczko, Sophia, Abdulla, Diana S.Y., Michels, Sebastian, Fischer, Rieke, Riedel, Richard, Weber, Jan-Philipp, Westphal, Theresa, Gerigk, Ulrich, Kern, Jens, Kaminsky, Britta, Randerath, Winfried, Kambartel, Karl-Otto, Merkelbach-Bruse, Sabine, Büttner, Reinhard, and Wolf, Jürgen

Published
2020
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12. Evaluation of BGJ398, a Fibroblast Growth Factor Receptor 1-3 Kinase Inhibitor, in Patients With Advanced Solid Tumors Harboring Genetic Alterations in Fibroblast Growth Factor Receptors: Results of a Global Phase I, Dose-Escalation and Dose-Expansion Study

Author

Nogova, Lucia, Sequist, Lecia V, Garcia, Jose Manuel Perez, Andre, Fabrice, Delord, Jean-Pierre, Hidalgo, Manuel, Schellens, Jan HM, Cassier, Philippe A, Camidge, D Ross, Schuler, Martin, Vaishampayan, Ulka, Burris, Howard A, Tian, G Gary, Campone, Mario, Wainberg, Zev A, Lim, Wan-Teck, LoRusso, Patricia, Shapiro, Geoffrey I, Parker, Katie, Chen, Xueying, Choudhury, Somesh, Ringeisen, Francois, Graus-Porta, Diana, Porter, Dale, Isaacs, Randi, Buettner, Reinhard, and Wolf, Jürgen

Subjects
Genetics, Cancer, Clinical Trials and Supportive Activities, Clinical Research, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, 6.2 Cellular and gene therapies, Adult, Aged, Aged, 80 and over, Antineoplastic Agents, Female, Humans, Hyperphosphatemia, Male, Maximum Tolerated Dose, Middle Aged, Phenylurea Compounds, Pyrimidines, Receptors, Fibroblast Growth Factor, Clinical Sciences, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

Purpose This two-part, first-in-human study was initiated in patients with advanced solid tumors harboring genetic alterations in fibroblast growth factor receptors (FGFRs) to determine the maximum tolerated dose (MTD), the recommended phase II dose (RP2D), and the schedule, safety, pharmacokinetics, pharmacodynamics, and antitumor activity of oral BGJ398, a selective FGFR1-3 tyrosine kinase inhibitor. Patients and Methods Adult patients were treated with escalating dosages of BGJ398 5 to 150 mg once daily or 50 mg twice daily continuously in 28-day cycles. During expansion at the MTD, patients with FGFR1-amplified squamous cell non-small-cell lung cancer (sqNSCLC; arm 1) or other solid tumors with FGFR genetic alterations (mutations/amplifications/fusions) received BGJ398 daily on a continuous schedule (arm 2), or on a 3-weeks-on/1-week-off schedule (arm 3). Results Data in 132 patients from the escalation and expansion arms are reported (May 15, 2015, cutoff). The MTD, 125 mg daily, was determined on the basis of dose-limiting toxicities in four patients (100 mg, grade 3 aminotransferase elevations [n = 1]; 125 mg, hyperphosphatemia [n = 1]; 150 mg, grade 1 corneal toxicity [n = 1] and grade 3 aminotransferase elevations [n = 1]). Common adverse events in patients treated at the MTD (n = 57) included hyperphosphatemia (82.5%), constipation (50.9%), decreased appetite (45.6%), and stomatitis (45.6%). A similar safety profile was observed using the 3-weeks-on/1-week-off schedule (RP2D). However, adverse event-related dose adjustments/interruptions were less frequent with the 3-weeks-on/1-week-off (50.0%) versus the continuous (73.7%) schedule. Antitumor activity (seven partial responses [six confirmed]) was demonstrated with BGJ398 doses ≥ 100 mg in patients with FGFR1-amplified sqNSCLC and FGFR3-mutant bladder/urothelial cancer. Conclusion BGJ398 at the MTD/RP2D had a tolerable and manageable safety profile and showed antitumor activity in several tumor types, including FGFR1-amplified sqNSCLC and FGFR3-mutant bladder/urothelial cancers.

Published
2017

13. Clonal dynamics of BRAF-driven drug resistance in EGFR-mutant lung cancer

Author

Schaufler, Diana, Ast, David F., Tumbrink, Hannah L., Abedpour, Nima, Maas, Lukas, Schwäbe, Ayla E., Spille, Inga, Lennartz, Stefanie, Fassunke, Jana, Aldea, Mihaela, Besse, Benjamin, Planchard, David, Nogova, Lucia, Michels, Sebastian, Kobe, Carsten, Persigehl, Thorsten, Westphal, Theresa, Koleczko, Sophia, Fischer, Rieke, Weber, Jan-Phillip, Altmüller, Janine, Thomas, Roman K., Merkelbach-Bruse, Sabine, Gautschi, Oliver, Mezquita, Laura, Büttner, Reinhard, Wolf, Jürgen, Peifer, Martin, Brägelmann, Johannes, Scheffler, Matthias, and Sos, Martin L.

Published
2021
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14. Rogaratinib in patients with advanced cancers selected by FGFR mRNA expression: a phase 1 dose-escalation and dose-expansion study

Author

Schuler, Martin, Cho, Byoung Chul, Sayehli, Cyrus Michael, Navarro, Alejandro, Soo, Ross A, Richly, Heike, Cassier, Philippe Alexandre, Tai, David, Penel, Nicolas, Nogova, Lucia, Park, Se Hoon, Schostak, Martin, Gajate, Pablo, Cathomas, Richard, Rajagopalan, Prabhu, Grevel, Joachim, Bender, Sebastian, Boix, Oliver, Nogai, Hendrik, Ocker, Matthias, Ellinghaus, Peter, and Joerger, Markus

Published
2019
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15. Safety and Efficacy of Crizotinib in Patients With Advanced or Metastatic ROS1-Rearranged Lung Cancer (EUCROSS): A European Phase II Clinical Trial

Author

Michels, Sebastian, Massutí, Bartomeu, Schildhaus, Hans-Ulrich, Franklin, Jeremy, Sebastian, Martin, Felip, Enriqueta, Grohé, Christian, Rodriguez-Abreu, Delvys, Abdulla, Diana S.Y., Bischoff, Helge, Brandts, Christian, Carcereny, Enric, Corral, Jesús, Dingemans, Anne-Marie C., Pereira, Eva, Fassunke, Jana, Fischer, Rieke N., Gardizi, Masyar, Heukamp, Lukas, Insa, Amelia, Kron, Anna, Menon, Roopika, Persigehl, Thorsten, Reck, Martin, Riedel, Richard, Rothschild, Sacha I., Scheel, Andreas H., Scheffler, Matthias, Schmalz, Petra, Smit, Egbert F., Limburg, Meike, Provencio, Mariano, Karachaliou, Niki, Merkelbach-Bruse, Sabine, Hellmich, Martin, Nogova, Lucia, Büttner, Reinhard, Rosell, Rafael, and Wolf, Jürgen

Published
2019
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16. K-ras Mutation Subtypes in NSCLC and Associated Co-occuring Mutations in Other Oncogenic Pathways

Author

Scheffler, Matthias, Ihle, Michaela A., Hein, Rebecca, Merkelbach-Bruse, Sabine, Scheel, Andreas H., Siemanowski, Janna, Brägelmann, Johannes, Kron, Anna, Abedpour, Nima, Ueckeroth, Frank, Schüller, Merle, Koleczko, Sophia, Michels, Sebastian, Fassunke, Jana, Pasternack, Helen, Heydt, Carina, Serke, Monika, Fischer, Rieke, Schulte, Wolfgang, Gerigk, Ulrich, Nogova, Lucia, Ko, Yon-Dschun, Abdulla, Diana S.Y., Riedel, Richard, Kambartel, Karl-Otto, Lorenz, Joachim, Sauerland, Imke, Randerath, Winfried, Kaminsky, Britta, Hagmeyer, Lars, Grohé, Christian, Eisert, Anna, Frank, Rieke, Gogl, Leonie, Schaepers, Carsten, Holzem, Alessandra, Hellmich, Martin, Thomas, Roman K., Peifer, Martin, Sos, Martin L., Büttner, Reinhard, and Wolf, Jürgen

Published
2019
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18. MET Fusions in NSCLC: Clinicopathologic Features and Response to MET Inhibition

Author

Riedel, Richard, primary, Fassunke, Jana, additional, Scheel, Andreas H., additional, Scheffler, Matthias, additional, Heydt, Carina, additional, Nogova, Lucia, additional, Michels, Sebastian, additional, Fischer, Rieke N., additional, Eisert, Anna, additional, Scharpenseel, Heather, additional, John, Felix, additional, Ruge, Lea, additional, Schaufler, Diana, additional, Siemanowski, Janna, additional, Ihle, Michaela A., additional, Wagener-Ryczek, Svenja, additional, Pappesch, Roberto, additional, Rehker, Jan, additional, Bunck, Anne, additional, Kobe, Carsten, additional, Keil, Felix, additional, Merkelbach-Bruse, Sabine, additional, Büttner, Reinhard, additional, and Wolf, Jürgen, additional

Published
2023
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19. MET Fusions in NSCLC: Clinicopathologic Features and Response to MET Inhibition

Author

Riedel, Richard, Fassunke, Jana, Scheel, Andreas H., Scheffler, Matthias, Heydt, Carina, Nogova, Lucia, Michels, Sebastian, Fischer, Rieke N., Eisert, Anna, Scharpenseel, Heather, John, Felix, Ruge, Lea, Schaufler, Diana, Siemanowski, Janna, Ihle, Michaela A., Wagener-Ryczek, Svenja, Pappesch, Roberto, Rehker, Jan, Bunck, Anne, Kobe, Carsten, Keil, Felix, Merkelbach-Bruse, Sabine, Büttner, Reinhard, and Wolf, Jürgen

Published
2024
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20. Data from Cell-Autonomous and Non–Cell-Autonomous Mechanisms of Transformation by Amplified FGFR1 in Lung Cancer

Author

Malchers, Florian, primary, Dietlein, Felix, primary, Schöttle, Jakob, primary, Lu, Xin, primary, Nogova, Lucia, primary, Albus, Kerstin, primary, Fernandez-Cuesta, Lynnette, primary, Heuckmann, Johannes M., primary, Gautschi, Oliver, primary, Diebold, Joachim, primary, Plenker, Dennis, primary, Gardizi, Masyar, primary, Scheffler, Matthias, primary, Bos, Marc, primary, Seidel, Danila, primary, Leenders, Frauke, primary, Richters, André, primary, Peifer, Martin, primary, Florin, Alexandra, primary, Mainkar, Prathama S., primary, Karre, Nagaraju, primary, Chandrasekhar, Srivari, primary, George, Julie, primary, Silling, Steffi, primary, Rauh, Daniel, primary, Zander, Thomas, primary, Ullrich, Roland T., primary, Reinhardt, H. Christian, primary, Ringeisen, Francois, primary, Büttner, Reinhard, primary, Heukamp, Lukas C., primary, Wolf, Jürgen, primary, and Thomas, Roman K., primary

Published
2023
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21. Supplementary Methods and Legends from Cell-Autonomous and Non–Cell-Autonomous Mechanisms of Transformation by Amplified FGFR1 in Lung Cancer

Author

Malchers, Florian, primary, Dietlein, Felix, primary, Schöttle, Jakob, primary, Lu, Xin, primary, Nogova, Lucia, primary, Albus, Kerstin, primary, Fernandez-Cuesta, Lynnette, primary, Heuckmann, Johannes M., primary, Gautschi, Oliver, primary, Diebold, Joachim, primary, Plenker, Dennis, primary, Gardizi, Masyar, primary, Scheffler, Matthias, primary, Bos, Marc, primary, Seidel, Danila, primary, Leenders, Frauke, primary, Richters, André, primary, Peifer, Martin, primary, Florin, Alexandra, primary, Mainkar, Prathama S., primary, Karre, Nagaraju, primary, Chandrasekhar, Srivari, primary, George, Julie, primary, Silling, Steffi, primary, Rauh, Daniel, primary, Zander, Thomas, primary, Ullrich, Roland T., primary, Reinhardt, H. Christian, primary, Ringeisen, Francois, primary, Büttner, Reinhard, primary, Heukamp, Lukas C., primary, Wolf, Jürgen, primary, and Thomas, Roman K., primary

Published
2023
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22. Supplementary Figures S1-S14 from Cell-Autonomous and Non–Cell-Autonomous Mechanisms of Transformation by Amplified FGFR1 in Lung Cancer

Author

Malchers, Florian, primary, Dietlein, Felix, primary, Schöttle, Jakob, primary, Lu, Xin, primary, Nogova, Lucia, primary, Albus, Kerstin, primary, Fernandez-Cuesta, Lynnette, primary, Heuckmann, Johannes M., primary, Gautschi, Oliver, primary, Diebold, Joachim, primary, Plenker, Dennis, primary, Gardizi, Masyar, primary, Scheffler, Matthias, primary, Bos, Marc, primary, Seidel, Danila, primary, Leenders, Frauke, primary, Richters, André, primary, Peifer, Martin, primary, Florin, Alexandra, primary, Mainkar, Prathama S., primary, Karre, Nagaraju, primary, Chandrasekhar, Srivari, primary, George, Julie, primary, Silling, Steffi, primary, Rauh, Daniel, primary, Zander, Thomas, primary, Ullrich, Roland T., primary, Reinhardt, H. Christian, primary, Ringeisen, Francois, primary, Büttner, Reinhard, primary, Heukamp, Lukas C., primary, Wolf, Jürgen, primary, and Thomas, Roman K., primary

Published
2023
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23. Implementation of Amplicon Parallel Sequencing Leads to Improvement of Diagnosis and Therapy of Lung Cancer Patients

Author

König, Katharina, Peifer, Martin, Fassunke, Jana, Ihle, Michaela A., Künstlinger, Helen, Heydt, Carina, Stamm, Katrin, Ueckeroth, Frank, Vollbrecht, Claudia, Bos, Marc, Gardizi, Masyar, Scheffler, Matthias, Nogova, Lucia, Leenders, Frauke, Albus, Kerstin, Meder, Lydia, Becker, Kerstin, Florin, Alexandra, Rommerscheidt-Fuss, Ursula, Altmüller, Janine, Kloth, Michael, Nürnberg, Peter, Henkel, Thomas, Bikár, Sven-Ernö, Sos, Martin L., Geese, William J., Strauss, Lewis, Ko, Yon-Dschun, Gerigk, Ulrich, Odenthal, Margarete, Zander, Thomas, Wolf, Jürgen, Merkelbach-Bruse, Sabine, Buettner, Reinhard, and Heukamp, Lukas C.

Published
2015
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25. METFusions in NSCLC: Clinicopathologic Features and Response to MET Inhibition

Author

Riedel, Richard, Fassunke, Jana, Scheel, Andreas H., Scheffler, Matthias, Heydt, Carina, Nogova, Lucia, Michels, Sebastian, Fischer, Rieke N., Eisert, Anna, Scharpenseel, Heather, John, Felix, Ruge, Lea, Schaufler, Diana, Siemanowski, Janna, Ihle, Michaela A., Wagener-Ryczek, Svenja, Pappesch, Roberto, Rehker, Jan, Bunck, Anne, Kobe, Carsten, Keil, Felix, Merkelbach-Bruse, Sabine, Büttner, Reinhard, and Wolf, Jürgen

Abstract

METfusions have been described only rarely in NSCLC. Thus, data on patient characteristics and treatment response are limited. We here report histopathologic data, patient demographics, and treatment outcome including response to MET tyrosine kinase inhibitor (TKI) therapy in METfusion-positive NSCLC.

Published
2024
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27. Screening of FGFR patients for FGFR directed clinical trials in Network Genomic Medicine (NGM): Real-world data.

Author

Scharpenseel, Heather, primary, Malchers, Florian, additional, Terjung, Inken, additional, Hillmer, Axel, additional, Merkelbach-Bruse, Sabine, additional, Scheel, Andreas H., additional, Siemanowski, Janna, additional, Scheffler, Matthias, additional, Riedel, Richard, additional, Eisert, Anna, additional, Michels, Sebastian Yves Friedrich, additional, Fischer, Rieke Nila, additional, Weber, Jan-Philip, additional, Westphal, Theresa, additional, Kron, Anna, additional, Sueptitz, Juliane, additional, Thomas, Roman K., additional, Buettner, Reinhard, additional, Wolf, Juergen, additional, and Nogova, Lucia, additional

Published
2022
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28. Metastatic patterns plus clinical and molecular characteristics of ROS1 aberrations in non-small cell lung cancer patients without rearrangements.

Author

Glaser, Moritz, primary, von Levetzow, Cornelia, additional, Michels, Sebastian Yves Friedrich, additional, Nogova, Lucia, additional, Katzenmeier, Marianna, additional, Wompner, Claudia, additional, Schmitz, Jaqueline, additional, Bitter, Elisabeth, additional, Terjung, Inken, additional, Passmann, Elke, additional, Schaufler, Diana, additional, Eisert, Anna, additional, Fischer, Rieke Nila, additional, Riedel, Richard, additional, Weber, Jan-Phillip, additional, Hahne, Sabine, additional, Merkelbach-Bruse, Sabine, additional, Büttner, Reinhard, additional, Wolf, Juergen, additional, and Scheffler, Matthias, additional

Published
2022
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29. Crizotinib in ROS1-rearranged lung cancer (EUCROSS): Updated overall survival.

Author

Michels, Sebastian Yves Friedrich, primary, Franklin, Jeremy, additional, Massuti, Bartomeu, additional, Sebastian, Martin, additional, Felip, Enriqueta, additional, Grohé, Christian, additional, Rodriguez-Abreu, Delvys, additional, Bischoff, Helge, additional, Carcereny, Enric, additional, Corral, Jesús, additional, Insa, Amelia, additional, Reck, Martin, additional, Rothschild, Sacha, additional, Provencio, Mariano, additional, Scheffler, Matthias, additional, Hellmich, Martin, additional, Nogova, Lucia, additional, Büttner, Reinhard, additional, Rosell, Rafael, additional, and Wolf, Juergen, additional

Published
2022
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30. Radiomics zur nicht-invasiven Bestimmung der PDL-1 Expression bei Patienten mit Hirnmetastasen bei nicht-kleinzelligem Lungenkrebs

Author

Meißner, Anna-Katharina, Gutsche, Robin, Galldiks, Norbert, Kocher, Martin, Jünger, Stephanie T., Eich, Marie-Lisa, Nogova, Lucia, Schmidt, Nils-Ole, Ruge, Maximilian I., Goldbrunner, Roland, Proescholdt, Martin, Grau, Stefan, and Lohmann, Philipp

Subjects
stomatognathic system, ddc: 610, Medicine and health
Abstract

Objective: The expression level of programmed cell death ligand 1 (PDL-1) might be an indicator for response to immunotherapy using checkpoint inhibitors in patients with non-small cell lung cancer (NSCLC). As intra-tumoral differences and discrepancies between the PDL-1 expression in the primary tumor [for full text, please go to the a.m. URL]

Published
2022

31. Reproducibility of dynamic contrast enhanced MRI derived transfer coefficient K-trans in lung cancer

Author

Weber, Jean-Philip Daniel, Spiro, Judith Eva, Scheffler, Matthias, Wolf, Juergen, Nogova, Lucia, Tittgemeyer, Marc, Maintz, David, Laue, Hendrik, Persigehl, Thorsten, Weber, Jean-Philip Daniel, Spiro, Judith Eva, Scheffler, Matthias, Wolf, Juergen, Nogova, Lucia, Tittgemeyer, Marc, Maintz, David, Laue, Hendrik, and Persigehl, Thorsten

Abstract

Dynamic contrast enhanced MRI (DCE-MRI) is a useful method to monitor therapy assessment in malignancies but must be reliable and comparable for successful clinical use. The aim of this study was to evaluate the inter- and intrarater reproducibility of DCE-MRI in lung cancer. At this IRB approved single centre study 40 patients with lung cancer underwent up to 5 sequential DCE-MRI examinations. DCE-MRI were performed using a 3.0T system. The volume transfer constant K-trans was assessed by three readers using the two-compartment Tofts model. Inter- and intrarater reliability and agreement was calculated by wCV, ICC and their 95% confident intervals. DCE-MRI allowed a quantitative measurement of K-trans in 107 tumors where 91 were primary carcinomas or intrapulmonary metastases and 16 were extrapulmonary metastases. K-trans showed moderate to good interrater reliability in overall measurements (ICC 0.716-0.841; wCV 30.3-38.4%). K-trans in pulmonary lesions >= 3 cm showed a good to excellent reliability (ICC 0.773-0.907; wCV 23.0-29.4%) compared to pulmonary lesions < 3 cm showing a moderate to good reliability (ICC 0.710-0.889; wCV 31.6-48.7%). K-trans in intrapulmonary lesions showed a good reliability (ICC 0.761-0.873; wCV 28.9-37.5%) compared to extrapulmonary lesions with a poor to moderate reliability (ICC 0.018-0.680; wCV 28.1-51.8%). The overall intrarater agreement was moderate to good (ICC 0.607-0.795; wCV 24.6-30.4%). With K-trans, DCE MRI offers a reliable quantitative biomarker for early non-invasive therapy assessment in lung cancer patients, but with a coefficient of variation of up to 48.7% in smaller lung lesions.

Published
2022

32. Targeted treatment of non-small cell lung cancer

Author

Scheffler, Matthias, Michels, Sebastian, Nogova, Lucia, Scheffler, Matthias, Michels, Sebastian, and Nogova, Lucia

Abstract

Non-small cell lung cancer (NSCLC) has made a remarkable development in recent decades with respect to its perception. In the late 1990s it was the problem child as the main cause of cancer with increasing tendencies, especially in women and with a pronounced stigmatization. It is now the role model as a biologically rational targeted treatment based on molecular dependencies of the tumor with a vast improvement of the traditionally poor survival times. Molecular tumor boards have long followed the NSCLC example in the assessment of targeted treatment approaches for other tumor entities. This review article gives an overview of the current possibilities for targeted treatment of NSCLC, which nowadays are applicable for nearly one third of all patients with NSCLC.

Published
2022

41. The Value of Multidisciplinary Neuro-oncological Tumor Boards to Increase the Accuracy of FET PET for Identifying Brain Tumor Relapse

Author

Ceccon, Garry S., Werner, Jan-Michael, Ruge, Maximilian I., Goldbrunner, Roland, Celik, Eren, Baues, Christian, Deckert, Martina, Brunn, Anna, Rongen, Manuel Montesinos, Büttner, Reinhard, Dunkl, Veronika, Nogova, Lucia, Schlamann, Marc, Kabbasch, Christoph, Rueß, Daniel, Hampl, Jürgen, Wollring, Michael M., Rosen, Elena K., Tscherpel, Caroline, Stoffels, Gabriele, Lohmann, Philipp, Mottaghy, Felix M., Fink, Gereon R., Langen, Karl-Josef, and Galldiks, Norbert

Published
2025
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42. KEAP1 mutations in squamous cell lung cancer.

Author

Koleczko, Sophia, Hillmer, Axel, Bayarassou, Abdel Hakim, Grohe, Christian, Buchenroth, Martin, Kaminsky, Britta, Schulte, Clemens, Michels, Sebastian Yves Friedrich, Schaufler, Diana, Kron, Anna, Riedel, Richard, Westphal, Theresa, Weber, Jan-Phillip, Fischer, Rieke Nila, Merkelbach-Bruse, Sabine, Nogova, Lucia, Buettner, Reinhard, Wolf, Juergen, Scheffler, Matthias, Koleczko, Sophia, Hillmer, Axel, Bayarassou, Abdel Hakim, Grohe, Christian, Buchenroth, Martin, Kaminsky, Britta, Schulte, Clemens, Michels, Sebastian Yves Friedrich, Schaufler, Diana, Kron, Anna, Riedel, Richard, Westphal, Theresa, Weber, Jan-Phillip, Fischer, Rieke Nila, Merkelbach-Bruse, Sabine, Nogova, Lucia, Buettner, Reinhard, Wolf, Juergen, and Scheffler, Matthias

Published
2021

44. KEAP1 mutations in squamous cell lung cancer.

Author

Koleczko, Sophia, primary, Hillmer, Axel, additional, Bayarassou, Abdel Hakim, additional, Grohé, Christian, additional, Buchenroth, Martin, additional, Kaminsky, Britta, additional, Schulte, Clemens, additional, Michels, Sebastian Yves Friedrich, additional, Schaufler, Diana, additional, Kron, Anna, additional, Riedel, Richard, additional, Westphal, Theresa, additional, Weber, Jan-Phillip, additional, Fischer, Rieke Nila, additional, Merkelbach-Bruse, Sabine, additional, Nogova, Lucia, additional, Buettner, Reinhard, additional, Wolf, Juergen, additional, and Scheffler, Matthias, additional

Published
2021
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45. Sorafenib and everolimus in patients with advanced solid tumors and KRAS‐mutated NSCLC: A phase I trial with early pharmacodynamic FDG‐PET assessment

Author

Nogova, Lucia, primary, Mattonet, Christian, additional, Scheffler, Matthias, additional, Taubert, Max, additional, Gardizi, Masyar, additional, Sos, Martin L., additional, Michels, Sebastian, additional, Fischer, Rieke N., additional, Limburg, Meike, additional, Abdulla, Diana S.Y., additional, Persigehl, Thorsten, additional, Kobe, Carsten, additional, Merkelbach‐Bruse, Sabine, additional, Franklin, Jeremy, additional, Backes, Heiko, additional, Schnell, Roland, additional, Behringer, Dirk, additional, Kaminsky, Britta, additional, Eichstaedt, Martina, additional, Stelzer, Christoph, additional, Kinzig, Martina, additional, Sörgel, Fritz, additional, Tian, Yingying, additional, Junge, Lisa, additional, Suleiman, Ahmed A., additional, Frechen, Sebastian, additional, Rokitta, Dennis, additional, Ouyang, Dongsheng, additional, Fuhr, Uwe, additional, Buettner, Reinhard, additional, and Wolf, Jürgen, additional

Published
2020
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46. Reproducibility of dynamic contrast enhanced MRI derived transfer coefficient Ktrans in lung cancer.

Author

Weber, Jean-Philip Daniel, Spiro, Judith Eva, Scheffler, Matthias, Wolf, Jürgen, Nogova, Lucia, Tittgemeyer, Marc, Maintz, David, Laue, Hendrik, and Persigehl, Thorsten

Subjects
CONTRAST-enhanced magnetic resonance imaging, LUNG cancer, MAGNETIC resonance imaging, LUNG diseases, INTER-observer reliability, CANCER patients
Abstract

Dynamic contrast enhanced MRI (DCE-MRI) is a useful method to monitor therapy assessment in malignancies but must be reliable and comparable for successful clinical use. The aim of this study was to evaluate the inter- and intrarater reproducibility of DCE-MRI in lung cancer. At this IRB approved single centre study 40 patients with lung cancer underwent up to 5 sequential DCE-MRI examinations. DCE-MRI were performed using a 3.0T system. The volume transfer constant Ktrans was assessed by three readers using the two-compartment Tofts model. Inter- and intrarater reliability and agreement was calculated by wCV, ICC and their 95% confident intervals. DCE-MRI allowed a quantitative measurement of Ktrans in 107 tumors where 91 were primary carcinomas or intrapulmonary metastases and 16 were extrapulmonary metastases. Ktrans showed moderate to good interrater reliability in overall measurements (ICC 0.716–0.841; wCV 30.3–38.4%). Ktrans in pulmonary lesions ≥ 3 cm showed a good to excellent reliability (ICC 0.773–0.907; wCV 23.0–29.4%) compared to pulmonary lesions < 3 cm showing a moderate to good reliability (ICC 0.710–0.889; wCV 31.6–48.7%). Ktrans in intrapulmonary lesions showed a good reliability (ICC 0.761–0.873; wCV 28.9–37.5%) compared to extrapulmonary lesions with a poor to moderate reliability (ICC 0.018–0.680; wCV 28.1–51.8%). The overall intrarater agreement was moderate to good (ICC 0.607–0.795; wCV 24.6–30.4%). With Ktrans, DCE MRI offers a reliable quantitative biomarker for early non-invasive therapy assessment in lung cancer patients, but with a coefficient of variation of up to 48.7% in smaller lung lesions. [ABSTRACT FROM AUTHOR]

Published
2022
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47. Phase I experience with rogaratinib in patients (pts) with urothelial carcinoma (UC) selected based on FGFR mRNA overexpression

Author

Kempf, Emmanuelle, Penel, Nicolas, Tournigand, Christophe, Gajate, Pablo, Tan, Daniel Shao-Weng, Cassier, Philippe, Nogova, Lucia, Cathomas, Richard, Schostak, Martin, Janitzky, Andreas, Wermke, Martin, Sayehli, Cyrus, Navarro, Alejandro, Park, Se Hoon, Piciu, Ana-Maria, Bender, Sebastian, Nogai, Hendrik, Ellinghaus, Peter, Joerger, Markus, Schuler, Martin H., Kempf, Emmanuelle, Penel, Nicolas, Tournigand, Christophe, Gajate, Pablo, Tan, Daniel Shao-Weng, Cassier, Philippe, Nogova, Lucia, Cathomas, Richard, Schostak, Martin, Janitzky, Andreas, Wermke, Martin, Sayehli, Cyrus, Navarro, Alejandro, Park, Se Hoon, Piciu, Ana-Maria, Bender, Sebastian, Nogai, Hendrik, Ellinghaus, Peter, Joerger, Markus, and Schuler, Martin H.

Published
2020

48. Sorafenib and everolimus in patients with advanced solid tumors and KRAS-mutated NSCLC: A phase I trial with early pharmacodynamic FDG-PET assessment

Author

Nogova, Lucia, Mattonet, Christian, Scheffler, Matthias, Taubert, Max, Gardizi, Masyar, Sos, Martin L., Michels, Sebastian, Fischer, Rieke N., Limburg, Meike, Abdulla, Diana S. Y., Persigehl, Thorsten, Kobe, Carsten, Merkelbach-Bruse, Sabine, Franklin, Jeremy, Backes, Heiko, Schnell, Roland, Behringer, Dirk, Kaminsky, Britta, Eichstaedt, Martina, Stelzer, Christoph, Kinzig, Martina, Soergel, Fritz, Tian, Yingying, Junge, Lisa, Suleiman, Ahmed A., Frechen, Sebastian, Rokitta, Dennis, Ouyang, Dongsheng, Fuhr, Uwe, Buettner, Reinhard, Wolf, Juergen, Nogova, Lucia, Mattonet, Christian, Scheffler, Matthias, Taubert, Max, Gardizi, Masyar, Sos, Martin L., Michels, Sebastian, Fischer, Rieke N., Limburg, Meike, Abdulla, Diana S. Y., Persigehl, Thorsten, Kobe, Carsten, Merkelbach-Bruse, Sabine, Franklin, Jeremy, Backes, Heiko, Schnell, Roland, Behringer, Dirk, Kaminsky, Britta, Eichstaedt, Martina, Stelzer, Christoph, Kinzig, Martina, Soergel, Fritz, Tian, Yingying, Junge, Lisa, Suleiman, Ahmed A., Frechen, Sebastian, Rokitta, Dennis, Ouyang, Dongsheng, Fuhr, Uwe, Buettner, Reinhard, and Wolf, Juergen

Abstract

Background Treatment of patients with solid tumors and KRAS mutations remains disappointing. One option is the combined inhibition of pathways involved in RAF-MEK-ERK and PI3K-AKT-mTOR. Methods Patients with relapsed solid tumors were treated with escalating doses of everolimus (E) 2.5-10.0 mg/d in a 14-day run-in phase followed by combination therapy with sorafenib (S) 800 mg/d from day 15. KRAS mutational status was assessed retrospectively in the escalation phase. Extension phase included KRAS-mutated non-small-cell lung cancer (NSCLC) only. Pharmacokinetic analyses were accompanied by pharmacodynamics assessment of E by FDG-PET. Efficacy was assessed by CT scans every 6 weeks of combination. Results Of 31 evaluable patients, 15 had KRAS mutation, 4 patients were negative for KRAS mutation, and the KRAS status remained unknown in 12 patients. Dose-limiting toxicity (DLT) was not reached. The maximum tolerated dose (MTD) was defined as 7.5 mg/d E + 800 mg/d S due to toxicities at previous dose level (10 mg/d E + 800 mg/d S) including leucopenia/thrombopenia III degrees and pneumonia III degrees occurring after the DLT interval. The metabolic response rate in FDG-PET was 17% on day 5 and 20% on day 14. No patient reached partial response in CT scan. Median progression free survival (PFS) and overall survival (OS) were 3.25 and 5.85 months, respectively. Conclusions Treatment of patients with relapsed solid tumors with 7.5 mg/d E and 800 mg/d S is safe and feasible. Early metabolic response in FDG-PET was not confirmed in CT scan several weeks later. The combination of S and E is obviously not sufficient to induce durable responses in patients with KRAS-mutant solid tumors.

Published
2020

50. Severe Pulmonary Toxicity in Patients With Advanced-Stage Hodgkinʼs Disease Treated With a Modified Bleomycin, Doxorubicin, Cyclophosphamide, Vincristine, Procarbazine, Prednisone, and Gemcitabine (BEACOPP) Regimen Is Probably Related to the Combination of Gemcitabine and Bleomycin: A Report of the German Hodgkinʼs Lymphoma Study Group

Author

Bredenfeld, Henning, Franklin, Jeremy, Nogova, Lucia, Josting, Andreas, Fries, S, Mailänder, Volker, Oertel, Joachim, Diehl, Volker, and Engert, Andreas

Published
2004
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