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101. KRASG12C/TP53 co-mutations identify long-term responders to first line palliative treatment with pembrolizumab monotherapy in PD-L1 high (≥50%) lung adenocarcinoma

Author

Frost, Nikolaj, primary, Kollmeier, Jens, additional, Vollbrecht, Claudia, additional, Grah, Christian, additional, Matthes, Burkhard, additional, Pultermann, Dennis, additional, von Laffert, Maximilian, additional, Lüders, Heike, additional, Olive, Elisabeth, additional, Raspe, Matthias, additional, Mairinger, Thomas, additional, Ochsenreither, Sebastian, additional, Blum, Torsten, additional, Hummel, Michael, additional, Suttorp, Norbert, additional, Witzenrath, Martin, additional, and Grohé, Christian, additional

Published
2021
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106. Relationship between clinical and radiological signs of bronchiectasis in COPD patients: Results from COSYCONET

Author

Kirsten Anne-Marie, Anne Wirz, Erich Traugott, Ficker Joachim H, Bertram J. Jobst, Vivien Janke, Stubbe Beate, Johanna I. Lutter, Barbara Ziss, Franziska C. Trudzinski, Patricia Berger, Henrik Watz, Gogol Manfred, Thomas Bahmer, Beate Polte, Kronsbein Juliane, Campus Kiel, Lange Christoph, Martina Seibert, Rudolf A. Jörres, Pfeifer Michael, Timmermann Hartmut, Grohé Christian, Tobias Welte, Studnicka Michael, Petra Hundack-Winter, Jana Graf, Jürgen Behr, Diana Schottel, Buhl Roland, Virchow J. Christian, Bewig Burkhard, Ruhrlandklinik gGmbH. Essen, Wirtz Hubert, Rosalie Untsch, Birte Struck, Peter Alter, Kathrin Kahnert, Gudrun Hübner, Vogelmeier Claus, Sabine Michalewski, Kropf-Sanchen Cornelia, Kenn Klaus, Pontus Mertsch, Sonja Rohweder, Hauck Rainer, Andreas Stefan, Ilona Kietzmann, Zabel Peter, Michaela Schrade-Illmann, Höffken Gerd, Julia Tobias, Frank Biertz, Seeger Werner, Manuel Klöser, Kahnert Kathrin, Teschler Helmut, Anita Reichel, Gina Spangel, Ulrike Rieber, Randerath Winfried J, Julia Teng, Tanja Lucke, Herth Felix, Jeanette Pieper, Lenka Krabbe, Taube Christian, Jürgen Biederer, Wagner Ulrich, Doris Lehnert, Claus Vogelmeier, Katrin Schwedler, Henke Markus, Jany Berthold, Katus Hugo A, Bals Robert, Zaklina Hinz, Cornelia Böckmann, Ellen Burmann, Margret Gleiniger, Behr Jürgen, Britta Markworth, Ewert Ralf, Gertraud Weiß, Katrin Wons, Barbara Arikan, Watz Henrik, Beate Schaufler, Lena Sterk, Robert Bals, Hans-Ulrich Kauczor, Koczulla Rembert, Held Matthias, and Welte Tobias

Subjects
Pulmonary and Respiratory Medicine, Male, medicine.medical_specialty, Copd patients, Medizin, Comorbidity, Severity of Illness Index, Pulmonary Disease, Chronic Obstructive, Medicine, Humans, In patient, Lung, Aged, Aged, 80 and over, COPD, Bronchiectasis, business.industry, Phlegm, Middle Aged, medicine.disease, Radiological weapon, Clinical diagnosis, Cohort, Female, Radiography, Thoracic, Radiology, medicine.symptom, business, Tomography, X-Ray Computed
Abstract

Bronchiectasis (BE) might be frequently present in COPD but masked by COPD symptoms. We studied the relationship of clinical signs of bronchiectasis to the presence and extent of its radiological signs in patients of different COPD severity. Visit 4 data (GOLD grades 1-4) of the COSYCONET cohort was used. Chest CT scans were evaluated for bronchiectasis in 6 lobes using a 3-point scale (0: absence, 1: ≤50%, 2: >50% BE-involvement for each lobe). 1176 patients were included (61%male, age 67.3y), among them 38 (3.2%) with reported physicians' diagnosis of bronchiectasis and 76 (6.5%) with alpha1-antitrypsin deficiency (AA1D). CT scans were obtained in 429 patients. Within this group, any signs of bronchiectasis were found in 46.6% of patients, whereby ≤50% BE occurred in 18.6% in ≤2 lobes, in 10.0% in 3-4 lobes, in 15.9% in 5-6 lobes; >50% bronchiectasis in at least 1 lobe was observed in 2.1%. Scores ≥4 correlated with an elevated ratio FRC/RV. The clinical diagnosis of bronchiectasis correlated with phlegm and cough and with radiological scores of at least 3, optimally ≥5. In COPD patients, clinical diagnosis and radiological signs of BE showed only weak correlations. Correlations became significant with increasing BE-severity implying radiological alterations in several lobes. This indicates the importance of reporting both presence and extent of bronchiectasis on CT. Further research is warranted to refine the criteria for CT scoring of bronchiectasis and to determine the relevance of radiologically but not clinically detectible bronchiectasis and their possible implications for therapy in COPD patients.

Published
2020

107. CAT score single item analysis in patients with COPD: results from COSYCONET

Author

J. Randerath Winfried, Pfeifer Michael, Kenn Klaus, Joachim H. Ficker, Gogol Manfred, Grohé Christian, Höffken Gerd, Zaklina Hinz, Julia Tobias, Henke Markus, Teschler Helmut, Welte Tobias, Benjamin Waschki, Buhl Roland, Paul W. Jones, Kirsten Anne-Marie, A. Katus Hugo, Taube Christian, Bewig Burkhard, Beate Polte, Kronsbein Juliane, Stubbe Beate, Bals Robert, Johanna I. Lutter, Sarah Marietta von Siemens, Lange Christoph, Vogelmeier Claus, Ellen Burmann, Wirtz Hubert, Kathrin Kahnert, Erich Traugott, Behr Jürgen, Birte Struck, Vivien Janke, Lenka Krabbe, Timmermann Hartmut, Wagner Ulrich, Anita Reichel, Sabine Michalewski, Gudrun Hübner, Seeger Werner, Doris Lehnert, Jany Berthold, Kropf-Sanchen Cornelia, Sandra Söhler, Jeanette Pieper, Ulrike Rieber, Peter Alter, Herth Felix, Zabel Peter, Andreas Stefan, Koczulla Rembert, Held Matthias, Tobias Welte, Franziska C. Trudzinski, Patricia Berger, Kahnert Kathrin, Jana Graf, Jürgen Behr, Rosalie Untsch, Rudolf A. Jörres, Kornelia Speth, Britta Markworth, Ewert Ralf, Gertraud Weiß, Hans-Ulrich Kauczor, Claus Vogelmeier, Katrin Schwedler, Katrin Wons, Bertram J. Jobst, Barbara Arikan, Margret Gleiniger, Henrik Watz, Watz Henrik, Studnicka Michael, Beate Schaufler, Diana Schottel, Sonja Rohweder, Robert Bals, Ilona Kietzmann, Virchow J. Christian, Burkhard Bewig, Hauck Rainer, and Michaela Schrade-Illmann

Subjects
Pulmonary and Respiratory Medicine, Percentile, medicine.medical_specialty, Medizin, Diagnostic Techniques, Respiratory System, Single item, CAT score, 03 medical and health sciences, Pulmonary Disease, Chronic Obstructive, 0302 clinical medicine, Internal medicine, medicine, COPD, In patient, 030212 general & internal medicine, Lung function, Emphysema, business.industry, Regression analysis, Cat Score, Copd, medicine.disease, Exploratory factor analysis, respiratory tract diseases, 030228 respiratory system, Cohort, business
Abstract

The COPD Assessment Test (CAT) is in widespread use for the evaluation of patients with chronic obstructive pulmonary disease (COPD). We assessed whether the CAT items carry additional information beyond the sum score regarding COPD characteristics including emphysema. Patients of GOLD grades 1 to 4 from the COPD cohort COSYCONET (German COPD and Systemic Consequences - Comorbidities Network) with complete CAT data were included (n = 2270), of whom 493 had chest CT evaluated for the presence of emphysema. Comorbidities and lung function were assessed following standardised procedures. Cross-sectional data analysis was based on multiple regression analysis of the single CAT items against a panel of comorbidities, lung function, or CT characteristics (qualitative score, 15th percentile of mean lung density), with age, BMI and gender as covariates. This was supported by exploratory factor analysis. Regarding the relationship to comorbidities and emphysema, there were marked differences between CAT items, especially items 1 and 2 versus 3 to 8. This grouping was basically confirmed by factor analysis. Items 4 and 5, and to a lower degree 1, 2 and 6, appeared to be informative regarding the presence of emphysema, whereas the total score was not or less informative. Regarding comorbidities, similar findings as for the total CAT score were obtained for the modified Medical Research Council scale (mMRC) which was also informative regarding emphysema. Our findings suggest that the usefulness of the CAT can be increased if evaluated on the basis of single items which may be indicating the presence of comorbidities and emphysema.

Published
2020

108. Stellungnahme zur Nutzenbewertung gemäß § 35a SGB V, veröffentlicht am 1. Dezember 2020, Vorgangsnummer 2020-09-01-D-558, IQWiG Bericht Nr. 1003

Author

Wörmann, Bernhard, Reck, Martin, Griesinger, Frank, Deutsche Krebsgesellschaft. Arbeitsgemeinschaft Für Internistische Onkologie, Deutsche Gesellschaft Für Pneumologie Und Beatmungsmedizin, Eberhardt, Wilfried E. E., Sebastian, Martin, Huber, Rudolf M., Schütte, Wolfgang, Gütz, Sylvia, Reinmuth, Niels, Deutsche Gesellschaft Für Hämatologie Und Medizinische Onkologie, Deutschland. Gemeinsamer Bundesausschuss, and Grohé, Christian

Subjects
Medizin und Gesundheit
Published
2020
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112. A Novel Sarcoidosis Risk Locus for Europeans on Chromosome 11q13.1

Author

Fischer, Annegret, Schmid, Benjamin, Ellinghaus, David, Nothnagel, Michael, Gaede, Karoline I., Schürmann, Manfred, Lipinski, Simone, Rosenstiel, Philip, Zissel, Gernot, Höhne, Kerstin, Petrek, Martin, Kolek, Vitezslav, Pabst, Stefan, Grohé, Christian, Grunewald, Johan, Ronninger, Marcus, Eklund, Anders, Padyukov, Leonid, Gieger, Christian, Wichmann, H.-Erich, Nebel, Almut, Franke, Andre, Müller-Quernheim, Joachim, Hofmann, Sylvia, and Schreiber, Stefan

Published
2012
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117. Nazartinib (EGF816) in patients with treatment-naïve EGFR-mutant non-small cell lung cancer (NSCLC): Updated phase II results.

Author

Tan, Daniel Shao-Weng, primary, Leighl, Natasha B., additional, Yang, James Chih-Hsin, additional, Riely, Gregory J., additional, Sequist, Lecia V., additional, Toyozawa, Ryo, additional, Wolf, Juergen, additional, Felip, Enriqueta, additional, Kim, Sang-We, additional, Ponce Aix, Santiago, additional, Smit, Egbert F., additional, Hida, Toyoaki, additional, Grohé, Christian, additional, Ghebremariam, Samson, additional, O’Sullivan-Djentuh, Leslie, additional, Belli, Riccardo, additional, Giovannini, Monica, additional, and Kim, Dong-Wan, additional

Published
2020
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118. Nintedanib + docetaxel in lung adenocarcinoma patients (pts) following treatment with immune checkpoint inhibitors (ICIs): Updated efficacy and safety results of the ongoing non-interventional study (NIS) VARGADO (NCT02392455).

Author

Grohé, Christian, primary, Blau, Wolfgang, additional, Gleiber, Wolfgang, additional, Haas, Siegfried, additional, Krüger, Stefan, additional, Mueller-Huesmann, Harald, additional, Schulze, Mathias, additional, Atz, Judith, additional, and Kaiser, Rolf, additional

Published
2020
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119. Pulmonary Hypertension in Adults with Congenital Heart Disease: Real-World Data from the International COMPERA-CHD Registry

Author

Kaemmerer, Harald, primary, Gorenflo, Matthias, additional, Huscher, Dörte, additional, Pittrow, David, additional, Apitz, Christian, additional, Baumgartner, Helmut, additional, Berger, Felix, additional, Bruch, Leonhard, additional, Brunnemer, Eva, additional, Budts, Werner, additional, Claussen, Martin, additional, Coghlan, Gerry, additional, Dähnert, Ingo, additional, D’Alto, Michele, additional, Delcroix, Marion, additional, Distler, Oliver, additional, Dittrich, Sven, additional, Dumitrescu, Daniel, additional, Ewert, Ralf, additional, Faehling, Martin, additional, Germund, Ingo, additional, Ghofrani, Hossein Ardeschir, additional, Grohé, Christian, additional, Grossekreymborg, Karsten, additional, Halank, Michael, additional, Hansmann, Georg, additional, Harzheim, Dominik, additional, Nemes, Attila, additional, Havasi, Kalman, additional, Held, Matthias, additional, M. Hoeper, Marius, additional, Hofbeck, Michael, additional, Hohenfrost-Schmidt, Wolfgang, additional, Jurevičienė, Elena, additional, Gumbienè, Lina, additional, Kabitz, Hans-Joachim, additional, Klose, Hans, additional, Köhler, Thomas, additional, Konstantinides, Stavros, additional, Köestenberger, Martin, additional, Kozlik-Feldmann, Rainer, additional, Kramer, Hans-Heiner, additional, Kropf-Sanchen, Cornelia, additional, Lammers, Astrid, additional, Lange, Tobias, additional, Meyn, Philipp, additional, Miera, Oliver, additional, Milger-Kneidinger, Katrin, additional, Neidenbach, Rhoia, additional, Neurohr, Claus, additional, Opitz, Christian, additional, Perings, Christian, additional, Remppis, Bjoern Andrew, additional, Riemekasten, Gabriele, additional, Scelsi, Laura, additional, Scholtz, Werner, additional, Simkova, Iveta, additional, Skowasch, Dirk, additional, Skride, Andris, additional, Stähler, Gerd, additional, Stiller, Brigitte, additional, Tsangaris, Iraklis, additional, Vizza, Carmine Dario, additional, Vonk Noordegraaf, Anton, additional, Wilkens, Heinrike, additional, Wirtz, Hubert, additional, Diller, Gerhard-Paul, additional, Grünig, Ekkehard, additional, and Rosenkranz, Stephan, additional

Published
2020
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120. Survival and course of lung function in the presence or absence of antifibrotic treatment in patients with idiopathic pulmonary fibrosis: long-term results of the INSIGHTS-IPF registry

Author

Behr, Jürgen, primary, Prasse, Antje, additional, Wirtz, Hubert, additional, Koschel, Dirk, additional, Pittrow, David, additional, Held, Matthias, additional, Klotsche, Jens, additional, Andreas, Stefan, additional, Claussen, Martin, additional, Grohé, Christian, additional, Wilkens, Henrike, additional, Hagmeyer, Lars, additional, Skowasch, Dirk, additional, Meyer, Joachim F., additional, Kirschner, Joachim, additional, Gläser, Sven, additional, Kahn, Nicolas, additional, Welte, Tobias, additional, Neurohr, Claus, additional, Schwaiblmair, Martin, additional, Bahmer, Thomas, additional, Oqueka, Tim, additional, Frankenberger, Marion, additional, and Kreuter, Michael, additional

Published
2020
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121. Antwort

Author

Wiesner, Barbara, additional and Grohé, Christian, additional

Published
2020
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128. Combined effects of lung function, blood gases and kidney function on the exacerbation risk in stable COPD: Results from the COSYCONET cohort

Author

F.C. Trudzinski, K. Kahnert, C.F. Vogelmeier, P. Alter, F. Seiler, S. Fähndrich, H. Watz, T. Welte, T. Speer, S. Zewinger, F. Biertz, H.-U. Kauczor, R.A. Jörres, R. Bals, Andreas Stefan, Bals Robert, Behr Jürgen, Kahnert Kathrin, Bewig Burkhard, Buhl Roland, Ewert Ralf, Stubbe Beate, Ficker Joachim H, Gogol Manfred, Grohé Christian, Hauck Rainer, Held Matthias, Jany Berthold, Henke Markus, Herth Felix, Höffken Gerd, Katus Hugo A, Kirsten Anne-Marie, Watz Henrik, Koczulla Rembert, Kenn Klaus, Kronsbein Juliane, Kropf-Sanchen Cornelia, Lange Christoph, Zabel Peter, Pfeifer Michael, Randerath Winfried J, null eeger Werner, Studnicka Michael, Taube Christian, Teschler Helmut, Timmermann Hartmut, Virchow J. Christian, Vogelmeier Claus, Wagner Ulrich, Welte Tobias, and Wirtz Hubert

Subjects
Pulmonary and Respiratory Medicine, Male, medicine.medical_specialty, Exacerbation, Partial Pressure, Medizin, Renal function, Comorbidity, Acid-Base Imbalance, Kidney Function Tests, Risk Assessment, Cohort Studies, 03 medical and health sciences, Pulmonary Disease, Chronic Obstructive, 0302 clinical medicine, DLCO, Diffusing capacity, Internal medicine, Forced Expiratory Volume, medicine, Humans, Respiratory function, 030212 general & internal medicine, Aged, COPD, Carbon Monoxide, business.industry, Middle Aged, medicine.disease, respiratory tract diseases, Respiratory Function Tests, Cross-Sectional Studies, 030228 respiratory system, Cohort, Cardiology, Disease Progression, Pulmonary Diffusing Capacity, Female, Blood Gas Analysis, Risk assessment, business, Glomerular Filtration Rate
Abstract

Rationale Alterations of acid-base metabolism are an important outcome predictor in acute exacerbations of COPD, whereas sufficient metabolic compensation and adequate renal function are associated with decreased mortality. In stable COPD there is, however, only limited information on the combined role of acid-base balance, blood gases, renal and respiratory function on exacerbation risk grading. Methods We used baseline data of the COPD cohort COSYCONET, applying linear and logistic regression analyses, the results of which were implemented into a comprehensive structural equation model. As most informative parameters it comprised the estimated glomerular filtration rate (eGFR), lung function defined via forced expiratory volume in 1 s (FEV1), intrathoracic gas volume (ITGV) and (diffusing capacity for carbon monoxide (DLCO), moreover arterial oxygen content (CaO2), partial pressure of oxygen (PaCO2), base exess (BE) and exacerbation risk according to GOLD criteria. All measures were adjusted for age, gender, body-mass index, the current smoking status and pack years. Results 1506 patients with stable COPD (GOLD grade 1–4; mean age 64.5 ± 8.1 y; mean FEV1 54 ± 18 %predicted, mean eGFR 82.3 ± 16.9 mL/min/1.73 m2) were included. BE was linked to eGFR, lung function and PaCO2 and played a role as indirect predictor of exacerbation risk via these measures; moreover, eGFR was directly linked to exacerbation risk. These associations remained significant after taking into account medication (diuretics, oral and inhaled corticosteroids), whereby corticosteroids had effects on exacerbation risk and lung function, diuretics on eGFR, BE and lung function. Conclusion Even in stable COPD acid-base metabolism plays a key integrative role in COPD risk assessment despite rather small deviations from normality. It partially mediates the effects of impairments in kidney function, which are also directly linked to exacerbation risk.

Published
2019

131. 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

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

Abstract

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.

Published
2024
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132. Additional file 2: of Epigenomic profiling of non-small cell lung cancer xenografts uncover LRP12 DNA methylation as predictive biomarker for carboplatin resistance

Author

Grasse, Sabrina, Lienhard, Matthias, Frese, Steffen, Kerick, Martin, Steinbach, Anne, Grimm, Christina, Hussong, Michelle, Rolff, Jana, Becker, Michael, Dreher, Felix, Schirmer, Uwe, Boerno, Stefan, Ramisch, Anna, Leschber, Gunda, Timmermann, Bernd, Grohé, Christian, Lüders, Heike, Vingron, Martin, Iduna Fichtner, Klein, Sebastian, Odenthal, Margarete, Büttner, Reinhard, Lehrach, Hans, Sültmann, Holger, Herwig, Ralf, and Schweiger, Michal

Abstract

Additional Methods. Figure S1. Region used for the MSP of LRP12. Figure S2. MeDIP-Seq statistics of 54 samples including primary tumor tissues (P) and PDXs (X). Table S3. MeDIP-Sequencing statistics. Table S4 Methyl-Sequencing statistics. Figure S3. Correlation of methylation of overlapping DMRs in primary NSCLC and patient-derived xenografts. Table S5. Tumor content of primary tumors and genome-wide Spearman correlation of DMRs of primary tissue to the PDXs. Figure S4. Patientwise circos plots of overlapping DMRs of primary NSCLC and PDX. Figure S5. Comparison of methylation values of primary NSCLCs and PDXs. Figure S6. Methylation differences between non-responders and responders in large hypomethylated blocks (LHBs) on chromosomes 1, 2, and 4 as examples. Table S6. Histopathologic evaluation of primary tumor and PDX tumor. Figure S7. Ingenuity pathway and upstream regulator analyses of the 2380 genes differentially methylated. Figure S8. LRP12 knockdown induces carboplatin resistance. Table S9. Patient’s data and clinical characteristics of the validation cohort. Figure S9. LRP12 DNA hypermethylation as independent factor predictive for clinical outcome in NSCLC. Figure S10 LRP12 DNA hypermethylation as independent predictive factor for clinical outcome in 449 NSCLC patients from the TCGA data set. Additional references. (XLSX 141 kb)

Published
2018
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133. Neuroendokrine Neoplasien im deutschen NET-Register

Author

Maasberg, Sebastian, Pape, Ulrich-Frank, Fottner, Christian, Goretzki, Peter E., Anlauf, Martin, Hörsch, Dieter, Cremer, Birgit, Schulte, Dominik M., Quietzsch, Detlef, Scheerer, Frank, Pöpperl, Gabriele, Pöppel, Thorsten, Begum, Nehara, Grohé, Christian, Rinke, Anja, Plöckinger, Ursula, Wiedenmann, Betram, Arnold, Rudolf, Neuhaus, Peter, Knapp, Wolfram H., Lehnert, Hendrick, Auernhammer, Christoph, Pavel, Marianne, Von Weikersthal, Ludwig Fischer, Schmidt, Bernd, Klein, Harald H., Essler, Markus, Neumann, Jörg-Dietrich, Hamann, Susanne, Steffens, Frank, Demtröder, Frank, Kröcher, Anke, Zoicas, Flavius, Lahner, Harald, Weber, Frank, Geiler, Michael, Raffel, Andreas, Krausch, Markus, Zimmermann, Patrick, Lerch, Markus M., Wirth, Thomas, Lang, Matthias, Ezziddin, Samer, Lammert, Frank, Bischoff, Marina, Altendorf-Hofmann, Annelore, Müller, Lothar, Hoffmeister, Albrecht, Klose, Silke, Musholt, Thomas J., Post, Stefan, Gertler, Ralf, Scheuerlein, Hubert, Bergmann, Tanja, Bisping, Guido, Knauerhase, Andreas, Rendenbach, Bernhard, Gro, Volker, Scheurlen, Michael, Mönig, Heiner, Kudlich, Theodor, Grabowski, Patricia, Watza, Felix, Scheidhauer, Klemens, and Möbius, Elke

Subjects
Gynecology, Neuroendocrine neoplasia, 03 medical and health sciences, medicine.medical_specialty, 0302 clinical medicine, business.industry, 030220 oncology & carcinogenesis, Gastroenterology, medicine, Medizin, 030209 endocrinology & metabolism, business
Abstract

ZusammenfassungNeuroendokrine Neoplasien (NEN) umfassen eine seltene Tumorentität mit heterogener Biologie, Prognose und therapeutischen Optionen. In Zusammenhang mit der kürzlichen Publikation der ersten deutschen Leitlinie zur Diagnostik und Therapie von NEN erfolgte die Analyse der Kohorte des Deutschen NET-Registers der Deutschen Gesellschaft für Endokrinologie (DGE). Hierzu wurden 2686 Fälle extrahiert und ihre Patientencharakteristika wie Alter, Geschlecht, Primärtumorlokalisation, Grading und Staging dargestellt sowie das Gesamtüberleben berechnet. Zusätzlich wurden die systemischen Behandlungsstrategien in den beiden größten Untergruppen, NEN des Dünndarms und Pankreas, im Stadium der Metastasierung analysiert.Die Verteilung der Primärtumoren, die histopathologische Charakterisierung, das Tumorstadium sowie das Gesamtüberleben waren vergleichbar mit den Ergebnissen internationaler Registerstudien. Somatostatinanaloga (SSA) und die Peptid-Rezeptor-Radionuklid-Therapie (PRRT) waren die häufigsten systemischen Therapieverfahren bei Dünndarm-NEN. Hingegen wurde eine Chemotherapie – in Übereinstimmung mit der neuen Leitlinie – vor allem bei pankreatischen NEN eingesetzt und kam in der Erstlinie in ähnlicher Frequenz wie die SSA-Therapie bzw. in der Zweitlinie ähnlich häufig wie eine PRRT zum Einsatz. Prognostisch relevante Parameter waren die WHO-Klassifikation 2010 und das TNM-Staging.Die aktuelle Analyse des deutschen NET-Registers charakterisiert damit eine multizentrische, interdisziplinäre, deutschlandweite Kohorte von NEN-Patienten und beschreibt die angewendeten systemischen Therapieverfahren, das Gesamtüberleben und die prognostische Bedeutung der WHO-Klassifikation 2010 sowie des TNM-Stadiums.

Published
2018

134. Late Breaking Abstract - Survival and course of lung function in patients with idiopathic pulmonary fibrosis with or without antifibrotic treatment: long-term results of the INSIGHTS-IPF registry

Author

Behr, Jürgen, primary, Wirtz, Hubert, additional, Pittrow, David, additional, Prasse, Antje, additional, Koschel, Dirk, additional, Geier, Silke, additional, Klotsche, Jens, additional, Andreas, Stefan, additional, Claussen, Martin, additional, Grohé, Christian, additional, Wilkens, Henrike, additional, Hagmeyer, Lars, additional, Skowasch, Dirk, additional, Meyer, Joachim F, additional, Kirschner, Joachim, additional, Gläser, Sven, additional, Kahn, Nicolas, additional, Welte, Tobias, additional, Neurohr, Claus, additional, Schwaiblmair, Martin, additional, Held, Matthias, additional, Bahmer, Thomas, additional, Oqueka, Tim, additional, Frankenberger, Marion, additional, and Kreuter, Michael, additional

Published
2019
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135. Neuroendokrine Neoplasien im deutschen NET-Register

Author

Maasberg, Sebastian, additional, Pape, Ulrich-Frank, additional, Fottner, Christian, additional, Goretzki, Peter E., additional, Anlauf, Martin, additional, Hörsch, Dieter, additional, Cremer, Birgit, additional, Schulte, Dominik M., additional, Quietzsch, Detlef, additional, Scheerer, Frank, additional, Pöpperl, Gabriele, additional, Poeppel, Thorsten D., additional, Begum, Nehara, additional, Grohé, Christian, additional, Rinke, Anja, additional, Plöckinger, Ursula, additional, Wiedenmann, Betram, additional, Arnold, Rudolf, additional, Neuhaus, Peter, additional, Knapp, Wolfram H., additional, Lehnert, Hendrick, additional, Auernhammer, Christoph, additional, Pavel, Marianne, additional, Weikersthal, Ludwig Fischer von, additional, Schmidt, Bernd, additional, Klein, Harald H., additional, Essler, Markus, additional, Neumann, Jörg-Dietrich, additional, Hamann, Susanne, additional, Steffens, Frank, additional, Demtröder, Frank, additional, Kröcher, Anke, additional, Zoicas, Flavius, additional, Lahner, Harald, additional, Weber, Frank, additional, Geißler, Michael, additional, Raffel, Andreas, additional, Krausch, Markus, additional, Zimmermann, Patrick, additional, Lerch, Markus M., additional, Wirth, Thomas, additional, Lang, Matthias, additional, Ezziddin, Samer, additional, Lammert, Frank, additional, Bischoff, Marina, additional, Altendorf-Hofmann, Annelore, additional, Müller, Lothar, additional, Hoffmeister, Albrecht, additional, Klose, Silke, additional, Musholt, Thomas J., additional, Post, Stefan, additional, Gertler, Ralf, additional, Scheuerlein, Hubert, additional, Bergmann, Tanja, additional, Bisping, Guido, additional, Knauerhase, Andreas, additional, Rendenbach, Bernhard, additional, Groß, Volker, additional, Scheurlen, Michael, additional, Mönig, Heiner, additional, Kudlich, Theodor, additional, Grabowski, Patricia, additional, Watza, Felix, additional, Scheidhauer, Klemens, additional, and Möbius, Elke, additional

Published
2019
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136. Nintedanib plus docetaxel after progression on immune checkpoint inhibitor therapy: insights from VARGADO, a prospective study in patients with lung adenocarcinoma

Author

Grohé, Christian, primary, Gleiber, Wolfgang, additional, Haas, Siegfried, additional, Losem, Christoph, additional, Mueller-Huesmann, Harald, additional, Schulze, Mathias, additional, Franke, Christian, additional, Basara, Nadezda, additional, Atz, Judith, additional, and Kaiser, Rolf, additional

Published
2019
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137. BIOLUMA: A phase II trial of nivolumab in combination with ipilimumab to evaluate efficacy and safety in lung cancer and to evaluate biomarkers predictive for response—Preliminary results from the SCLC cohort.

Author

Fischer, Rieke Nila, primary, George, Julie, additional, Scheel, Andreas H., additional, Schloesser, Hans Anton, additional, Vehreschild, Maria, additional, Brossart, Peter, additional, Engel-Riedel, Walburga, additional, Griesinger, Frank, additional, Grohé, Christian, additional, Kambartel, Karl-Otto, additional, Kern, Jens, additional, Hermes, Barbara, additional, Nachtkamp, Kathrin, additional, Panse, Jens Peter, additional, Sebastian, Martin, additional, Lehmann, Markus, additional, Wiewrodt, Rainer Gerhard, additional, Büttner, Reinhard, additional, Thomas, Roman K., additional, and Wolf, Juergen, additional

Published
2019
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138. BIOLUMA: A phase II trial of nivolumab in combination with ipilimumab to evaluate efficacy and safety in lung cancer and to evaluate biomarkers predictive for response—Preliminary results from the NSCLC cohort.

Author

Fischer, Rieke Nila, primary, George, Julie, additional, Scheel, Andreas H., additional, Schloesser, Hans Anton, additional, Vehreschild, Maria, additional, Brossart, Peter, additional, Engel-Riedel, Walburga, additional, Griesinger, Frank, additional, Grohé, Christian, additional, Kambartel, Karl-Otto, additional, Kern, Jens, additional, Hermes, Barbara, additional, Nachtkamp, Kathrin, additional, Panse, Jens Peter, additional, Sebastian, Martin, additional, Lehmann, Markus, additional, Wiewrodt, Rainer Gerhard, additional, Büttner, Reinhard, additional, Thomas, Roman K., additional, and Wolf, Juergen, additional

Published
2019
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139. Nintedanib plus docetaxel in lung adenocarcinoma patients (pts) following treatment with immune checkpoint inhibitors (ICIs): Preliminary efficacy and safety results of the non-interventional study VARGADO.

Author

Grohé, Christian, primary, Blau, Wolfgang, additional, Gleiber, Wolfgang, additional, Haas, Siegfried, additional, Mueller-Huesmann, Harald, additional, Schulze, Mathias, additional, Atz, Judith, additional, and Kaiser, Rolf, additional

Published
2019
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140. Defining aggressive or early progressing nononcogene-addicted non-small-cell lung cancer: a separate disease entity?

Author

Reck, Martin, primary, Kerr, Keith M, additional, Grohé, Christian, additional, Manegold, Christian, additional, Pavlakis, Nick, additional, Paz-Ares, Luis, additional, Huber, Rudolf M, additional, Popat, Sanjay, additional, Thatcher, Nick, additional, Park, Keunchil, additional, Hilberg, Frank, additional, Barrueco, José, additional, and Kaiser, Rolf, additional

Published
2019
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142. Chronic thromboembolic pulmonary hypertension (CTEPH): Updated Recommendations from the Cologne Consensus Conference 2018

Author

Wilkens, Heinrike, primary, Konstantinides, Stavros, additional, Lang, Irene M., additional, Bunck, Alexander C., additional, Gerges, Mario, additional, Gerhardt, Felix, additional, Grgic, Aleksandar, additional, Grohé, Christian, additional, Guth, Stefan, additional, Held, Matthias, additional, Hinrichs, Jan B., additional, Hoeper, Marius M., additional, Klepetko, Walter, additional, Kramm, Thorsten, additional, Krüger, Ulrich, additional, Lankeit, Mareike, additional, Meyer, Bernhard C., additional, Olsson, Karen M., additional, Schäfers, Hans-Joachim, additional, Schmidt, Matthias, additional, Seyfarth, Hans-J, additional, Ulrich, Silvia, additional, Wiedenroth, Christoph B., additional, and Mayer, Eckhard, additional

Published
2018
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143. Local ablative treatment for synchronous single organ oligometastatic lung cancer—A propensity score analysis of 180 patients

Author

Frost, Nikolaj, primary, Tessmer, Antje, additional, Schmittel, Alexander, additional, van Laak, Vincent, additional, Raspe, Matthias, additional, Ruwwe-Glösenkamp, Christoph, additional, Brunn, Matthias, additional, Senger, Carolin, additional, Böhmer, Dirk, additional, Ochsenreither, Sebastian, additional, Temmesfeld-Wollbrück, Bettina, additional, Furth, Christian, additional, Schmidt, Bernd, additional, Neudecker, Jens, additional, Rückert, Jens-Carsten, additional, Suttorp, Norbert, additional, Witzenrath, Martin, additional, and Grohé, Christian, additional

Published
2018
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144. CpG oligonucleotide activates Toll-like receptor 9 and causes lung inflammation in vivo

Author

Hoeft Andreas, Meyer Rainer, Mersmann Jan, Ehrentraut Heidi, Velten Markus, Schwederski Markus, Koch Alexander, Baumgarten Georg, Knuefermann Pascal, Zacharowski Kai, and Grohé Christian

Subjects
Diseases of the respiratory system, RC705-779
Abstract

Abstract Background Bacterial DNA containing motifs of unmethylated CpG dinucleotides (CpG-ODN) initiate an innate immune response mediated by the pattern recognition receptor Toll-like receptor 9 (TLR9). This leads in particular to the expression of proinflammatory mediators such as tumor necrosis factor (TNF-α) and interleukin-1β (IL-1β). TLR9 is expressed in human and murine pulmonary tissue and induction of proinflammatory mediators has been linked to the development of acute lung injury. Therefore, the hypothesis was tested whether CpG-ODN administration induces an inflammatory response in the lung via TLR9 in vivo. Methods Wild-type (WT) and TLR9-deficient (TLR9-D) mice received CpG-ODN intraperitoneally (1668-Thioat, 1 nmol/g BW) and were observed for up to 6 hrs. Lung tissue and plasma samples were taken and various inflammatory markers were measured. Results In WT mice, CpG-ODN induced a strong activation of pulmonary NFκB as well as a significant increase in pulmonary TNF-α and IL-1β mRNA/protein. In addition, cytokine serum levels were significantly elevated in WT mice. Increased pulmonary content of lung myeloperoxidase (MPO) was documented in WT mice following application of CpG-ODN. Bronchoalveolar lavage (BAL) revealed that CpG-ODN stimulation significantly increased total cell number as well as neutrophil count in WT animals. In contrast, the CpG-ODN-induced inflammatory response was abolished in TLR9-D mice. Conclusion This study suggests that bacterial CpG-ODN causes lung inflammation via TLR9.

Published
2007
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145. Additional file 1: Table S1. of Health related quality of life in patients with idiopathic pulmonary fibrosis in clinical practice: insights-IPF registry

Author

Kreuter, Michael, Swigris, Jeff, Pittrow, David, Geier, Silke, Klotsche, Jens, Prasse, Antje, Wirtz, Hubert, Koschel, Dirk, Andreas, Stefan, Claussen, Martin, Grohé, Christian, Wilkens, Henrike, Hagmeyer, Lars, Skowasch, Dirk, Meyer, Joachim, Kirschner, Joachim, Gläser, Sven, Herth, Felix, Welte, Tobias, Neurohr, Claus, Schwaiblmair, Martin, Held, Matthias, Bahmer, Thomas, Frankenberger, Marion, and Behr, Jürgen

Subjects
humanities
Abstract

Comparison of baseline characteristics of patients with and without available QoL data (total enrolled patients n = 737). (DOCX 15 kb)

Published
2017
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146. Outcome of First-Line Treatment With Pembrolizumab According to KRAS/TP53Mutational 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, Stenzinger, Albrecht, Stephan-Falkenau, Susann, Trautmann, Marcel, Lassmann, Silke, Tiemann, Markus, Klauschen, Frederick, Sebastian, Martin, Griesinger, Frank, Wolf, Jürgen, Loges, Sonja, Frost, Nikolaj, 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, and Schütte, Wolfgang

Abstract

Programmed death-ligand 1 expression currently represents the only validated predictive biomarker for immune checkpoint inhibition in metastatic NSCLC in the clinical routine, but it has limited value in distinguishing responses. Assessment of KRASand TP53mutations (mut) as surrogate for an immunosupportive tumor microenvironment (TME) might help to close this gap.

Published
2024
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147. Health-related quality of life associates with change in FEV1 in COPD: results from the COSYCONET cohort.

Author

Lutter, Johanna I., Jörres, Rudolf A., Kahnert, Kathrin, Schwarzkopf, Larissa, Studnicka, Michael, Karrasch, Stefan, Schulz, Holger, Vogelmeier, Claus F., Holle, Rolf, for the COSYCONET Study Group, Andreas, Stefan, Bals, Robert, Behr, Jürgen, Bewig, Burkhard, Buhl, Roland, Ewert, Ralf, Stubbe, Beate, Ficker, Joachim H., Gogol, Manfred, and Grohé, Christian

Subjects
OBSTRUCTIVE lung diseases, QUALITY of life, VISUAL analog scale
Abstract

Background: Forced expiratory volume in one second (FEV1) characterizes the pathophysiology of COPD and different trajectories of FEV1 decline have been observed in patients with COPD (e.g. gradual or episodic). There is limited information about the development of patient-reported health-related quality of life (HRQL) over the full range of the natural history of COPD. We examined the longitudinal association between change in FEV1 and change in disease-specific and generic HRQL.Methods: We analysed data of 1734 patients with COPD participating in the COSYCONET cohort with up to 3 years of follow-up. Patients completed the Saint George's Respiratory Questionnaire (SGRQ) and the EQ-5D Visual Analog Scale (EQ VAS). Change score models were used to investigate the relationship between HRQL and FEV1 and to calculate mean changes in HRQL per FEV1 change categories [decrease (≤ - 100 ml), no change, increase (≥ 100 ml)] after 3 years. Applying hierarchical linear models (HLM), we estimated the cross-sectional between-subject difference and the longitudinal within-subject change of HRQL as related to a FEV1 difference or change.Results: We observed a statistically significant deterioration in SGRQ (total score + 1.3 units) after 3 years, which was completely driven by the activity component (+ 4 units). No significant change was found for the generic EQ VAS. Over the same period, 58% of patients experienced a decrease in FEV1, 28% were recorded as no change in FEV1, and 13% experienced an increase. The relationship between HRQL and FEV1 was found to be approximately linear with decrease in FEV1 being statistically significantly associated with a deterioration in SGRQ (+ 3.20 units). Increase in FEV1 was associated with improvements in SGRQ (- 3.81 units). The associations between change in FEV1 and the EQ VAS were similar. Results of the HLMs were consistent and highly statistically significant, indicating cross-sectional and longitudinal associations. The largest estimates were found for the association between FEV1 and the SGRQ activity domain.Conclusions: Difference and change in FEV1 over time correlate with difference and change in disease-specific and generic HRQL. We conclude, that deterioration of HRQL should induce timely re-examination of physical status and lung function and possibly reassessment of therapeutic regimes.Trial Registration: NCT01245933. Date of registration: 18 November 2010. [ABSTRACT FROM AUTHOR]

Published
2020
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149. Large cell neuroendocrine lung carcinoma induces peripheral T-cell repertoire alterations with predictive and prognostic significance

Author

Christopoulos, Petros, primary, Schneider, Marc A., additional, Bozorgmehr, Farastuk, additional, Kuon, Jonas, additional, Engel-Riedel, Walburga, additional, Kollmeier, Jens, additional, Baum, Volker, additional, Muley, Thomas, additional, Schnabel, Philipp A., additional, Bischoff, Helge, additional, Grohé, Christian, additional, Serke, Monika, additional, Thomas, Michael, additional, Fisch, Paul, additional, and Meister, Michael, additional

Published
2018
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