415 results on '"Juergen Wolf"'
Search Results
2. Co-mutations and KRAS G12C inhibitor efficacy in advanced NSCLC
- Author
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Marcelo V. Negrao, Haniel A. Araujo, Giuseppe Lamberti, Alissa J. Cooper, Neal S. Akhave, Teng Zhou, Lukas Delasos, J Kevin. Hicks, Mihaela Aldea, Gabriele Minuti, Jacobi Hines, Jacqueline V. Aredo, Michael J. Dennis, Turja Chakrabarti, Susan C. Scott, Paolo Bironzo, Matthias Scheffler, Petros Christopoulos, Albrecht Stenzinger, Jonathan W. Riess, So Yeon Kim, Sarah B. Goldberg, Mingjia Li, Qi Wang, Yun Qing, Ying Ni, Minh Truong Do, Richard Lee, Biagio Ricciuti, Joao Victor. Alessi, Jing Wang, Blerina Resuli, Lorenza Landi, Shu-Chi Tseng, Mizuki Nishino, Subba R. Digumarthy, Waree Rinsurongkawong, Vadeerat Rinsurongkawong, Ara A Vaporciyan, George R. Blumenschein, Jianjun Zhang, Dwight H. Owen, Collin M. Blakely, Giannis Mountzios, Catherine A. Shu, Christine M. Bestvina, Marina Chiara. Garassino, Kristen A. Marrone, Jhanelle E. Gray, Sandip Pravin. Patel, Amy L. Cummings, Heather A. Wakelee, Juergen Wolf, Giorgio Vittorio. Scagliotti, Federico Cappuzzo, Fabrice Barlesi, Pradnya D. Patil, Leylah Drusbosky, Don L. Gibbons, Funda Meric-Bernstam, J. Jack Lee, John V. Heymach, David S. Hong, Rebecca S. Heist, Mark M. Awad, and Ferdinandos Skoulidis
- Subjects
Oncology - Abstract
Molecular modifiers of KRAS G12C inhibitor (KRAS G12Ci) efficacy in advanced KRAS G12C-mutant NSCLC are poorly defined. In a large unbiased clinico-genomic analysis of 424 NSCLC patients, we identified and validated co-alterations in KEAP1, SMARCA4 and CDKN2A as major independent determinants of inferior clinical outcomes with KRAS G12Ci monotherapy. Collectively, co-mutations in these three tumor suppressor genes segregated patients into distinct prognostic subgroups and captured ~50% of those with early disease progression (PFS≤3 months) with KRAS G12Ci. Pathway-level integration of less prevalent co-alterations in functionally related genes nominated PI3K/AKT/MTOR pathway and additional baseline RAS gene alterations, including amplifications, as candidate drivers of inferior outcomes with KRAS G12Ci, and revealed a possible association between defective DNA damage response/repair and improved KRAS G12Ci efficacy. Our findings propose a framework for patient stratification and clinical outcome prediction in KRAS G12C-mutant NSCLC that can inform rational selection and appropriate tailoring of emerging combination therapies.
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- 2023
3. Supplementary Data from Pan-Cancer Efficacy of Vemurafenib in BRAFV600-Mutant Non-Melanoma Cancers
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David M. Hyman, Bethany Pitcher, Todd Riehl, Eric J. Sherman, Gregory J. Riely, Eli L. Diamond, Jason Roszik, Funda Meric-Bernstam, José Baselga, Juergen Wolf, Noopur S. Raje, A. Craig Lockhart, Ian Chau, Jean-Yves Blay, Igor Puzanov, and Vivek Subbiah
- Abstract
Supplementary figures 1 & 2
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- 2023
4. Data from Pan-Cancer Efficacy of Vemurafenib in BRAFV600-Mutant Non-Melanoma Cancers
- Author
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David M. Hyman, Bethany Pitcher, Todd Riehl, Eric J. Sherman, Gregory J. Riely, Eli L. Diamond, Jason Roszik, Funda Meric-Bernstam, José Baselga, Juergen Wolf, Noopur S. Raje, A. Craig Lockhart, Ian Chau, Jean-Yves Blay, Igor Puzanov, and Vivek Subbiah
- Abstract
BRAFV600 mutations occur in a wide range of tumor types, and RAF inhibition has become standard in several of these cancers. Despite this progress, BRAFV600 mutations have historically been considered a clear demonstration of tumor lineage context–dependent oncogene addiction, based predominantly on the insensitivity to RAF inhibition in colorectal cancer. However, the true broader activity of RAF inhibition pan-cancer remains incompletely understood. To address this, we conducted a multicohort “basket” study of the BRAF inhibitor vemurafenib in non-melanoma BRAFV600 mutation–positive solid tumors. In total, 172 patients with 26 unique cancer types were treated, achieving an overall response rate of 33% and median duration of response of 13 months. Responses were observed in 13 unique cancer types, including historically treatment-refractory tumor types such as cholangiocarcinoma, sarcoma, glioma, neuroendocrine carcinoma, and salivary gland carcinomas. Collectively, these data demonstrate that single-agent BRAF inhibition has broader clinical activity than previously recognized.Significance:These data suggest that BRAFV600 mutations lead to oncogene addiction and are clinically actionable in a broad range of non-melanoma cancers, including tumor types in which RAF inhibition is not currently considered standard of care.See related commentary by Ribas and Lo, p. 640.This article is highlighted in the In This Issue feature, p. 627
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- 2023
5. Supplementary Table 1 from Pan-Cancer Efficacy of Vemurafenib in BRAFV600-Mutant Non-Melanoma Cancers
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David M. Hyman, Bethany Pitcher, Todd Riehl, Eric J. Sherman, Gregory J. Riely, Eli L. Diamond, Jason Roszik, Funda Meric-Bernstam, José Baselga, Juergen Wolf, Noopur S. Raje, A. Craig Lockhart, Ian Chau, Jean-Yves Blay, Igor Puzanov, and Vivek Subbiah
- Abstract
Supplementary Table 1
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- 2023
6. protocol_2018.789990.pdf from Pan-Cancer Efficacy of Vemurafenib in BRAFV600-Mutant Non-Melanoma Cancers
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David M. Hyman, Bethany Pitcher, Todd Riehl, Eric J. Sherman, Gregory J. Riely, Eli L. Diamond, Jason Roszik, Funda Meric-Bernstam, José Baselga, Juergen Wolf, Noopur S. Raje, A. Craig Lockhart, Ian Chau, Jean-Yves Blay, Igor Puzanov, and Vivek Subbiah
- Abstract
Protocol appendix
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- 2023
7. Supplementary Tables from Combined VEGF and PD-L1 Blockade Displays Synergistic Treatment Effects in an Autochthonous Mouse Model of Small Cell Lung Cancer
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Roland T. Ullrich, H. Christian Reinhardt, Michael von Bergwelt-Baildon, Marco Herling, Michael Hallek, Juergen Wolf, Reinhard Buettner, Margarete Odenthal, Hans A. Schlößer, Kristina Golfmann, Alexandra Florin, Richard Riedel, Sebastian Oberbeck, Ignacija Vlasic, Kerstin Wennhold, Sven Borchmann, Sebastian Klein, Felix Dietlein, Anna Schmitt, Martin Thelen, Philipp Schuldt, and Lydia Meder
- Abstract
Clinicopathologic parameters of mice and patients with the corresponding survival significance analysis of SCLC bearing mice treated with vehicle, IgG control, anti-VEGF monotherapy, anti-PD-L1 monotherapy or anti-VEGF/anti-PD-L1 combination therapy
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- 2023
8. Data from Combined VEGF and PD-L1 Blockade Displays Synergistic Treatment Effects in an Autochthonous Mouse Model of Small Cell Lung Cancer
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Roland T. Ullrich, H. Christian Reinhardt, Michael von Bergwelt-Baildon, Marco Herling, Michael Hallek, Juergen Wolf, Reinhard Buettner, Margarete Odenthal, Hans A. Schlößer, Kristina Golfmann, Alexandra Florin, Richard Riedel, Sebastian Oberbeck, Ignacija Vlasic, Kerstin Wennhold, Sven Borchmann, Sebastian Klein, Felix Dietlein, Anna Schmitt, Martin Thelen, Philipp Schuldt, and Lydia Meder
- Abstract
Small cell lung cancer (SCLC) represents the most aggressive pulmonary neoplasm and is often diagnosed at late stage with limited survival, despite combined chemotherapies. We show in an autochthonous mouse model of SCLC that combined anti-VEGF/anti-PD-L1–targeted therapy synergistically improves treatment outcome compared with anti–PD-L1 and anti-VEGF monotherapy. Mice treated with anti–PD-L1 alone relapsed after 3 weeks and were associated with a tumor-associated PD-1/TIM-3 double-positive exhausted T-cell phenotype. This exhausted T-cell phenotype upon PD-L1 blockade was abrogated by the addition of anti-VEGF–targeted treatment. We confirmed a similar TIM-3–positive T-cell phenotype in peripheral blood mononuclear cells of patients with SCLC with adaptive resistance to anti–PD-1 treatment. Mechanistically, we show that VEGFA enhances coexpression of the inhibitory receptor TIM-3 on T cells, indicating an immunosuppressive function of VEGF in patients with SCLC during anti–PD-1-targeted treatment. Our data strongly suggest that a combination of anti-VEGF and anti–PD-L1 therapies can be an effective treatment strategy in patients with SCLC.Significance: Combining VEGF and PD-L1 blockade could be of therapeutic benefit to patients with small cell lung cancer. Cancer Res; 78(15); 4270–81. ©2018 AACR.
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- 2023
9. Supplementary Figures from Combined VEGF and PD-L1 Blockade Displays Synergistic Treatment Effects in an Autochthonous Mouse Model of Small Cell Lung Cancer
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Roland T. Ullrich, H. Christian Reinhardt, Michael von Bergwelt-Baildon, Marco Herling, Michael Hallek, Juergen Wolf, Reinhard Buettner, Margarete Odenthal, Hans A. Schlößer, Kristina Golfmann, Alexandra Florin, Richard Riedel, Sebastian Oberbeck, Ignacija Vlasic, Kerstin Wennhold, Sven Borchmann, Sebastian Klein, Felix Dietlein, Anna Schmitt, Martin Thelen, Philipp Schuldt, and Lydia Meder
- Abstract
Supplementary data supporting an exhausted T cell phenotype in SCLC upon acquired resistance to PD1/PD-L1 blockade which is regulated by VEGF/VEGFR signaling and in addition, an immunosuppressive role of tumor-associated macrophages in the tumor microenvironment
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- 2023
10. Corrosion study on Cu/Sn-Ag solid-liquid interdiffusion microbumps by salt spray testing with 5 wt.% NaCl solution
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Laura Wenzel, Maik Mueller, Iuliana Panchenko, Wolfram Steller, and M. Juergen Wolf
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- 2022
11. Second-line nivolumab in relapsed small-cell lung cancer: CheckMate 331☆
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N. Pardo Aranda, Clarisse Audigier-Valette, Juergen Wolf, David Vicente, Scott J. Antonia, Dimple Pandya, Kazuhiko Nakagawa, David R. Spigel, Solange Peters, Alexander Luft, M. Shi, Ying Cheng, O. Juan-Vidal, Scott N. Gettinger, Martin Reck, J. Fairchild, Parul Doshi, Tudor-Eliade Ciuleanu, Leora Horn, Han Chang, Christine Baudelet, and H. Zhang
- Subjects
0301 basic medicine ,Oncology ,medicine.medical_specialty ,Lung Neoplasms ,endocrine system diseases ,medicine.medical_treatment ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,PD-1 ,Antineoplastic Combined Chemotherapy Protocols ,small-cell lung cancer ,Clinical endpoint ,Humans ,Medicine ,Lung cancer ,neoplasms ,Chemotherapy ,business.industry ,Hazard ratio ,biomarkers ,Hematology ,medicine.disease ,Small Cell Lung Carcinoma ,Progression-Free Survival ,humanities ,Confidence interval ,respiratory tract diseases ,PD-1, biomarkers, immunotherapy, small-cell lung cancer ,Nivolumab ,030104 developmental biology ,030220 oncology & carcinogenesis ,Topotecan ,immunotherapy ,Neoplasm Recurrence, Local ,business ,Amrubicin ,medicine.drug - Abstract
Patients with relapsed small-cell lung cancer (SCLC) have few treatment options and dismal survival. Phase I/II data show activity of nivolumab in previously treated SCLC.CheckMate 331 is a randomized, open-label, phase III trial of nivolumab versus standard chemotherapy in relapsed SCLC. Patients with relapse after first-line, platinum-based chemotherapy were randomized 1 : 1 to nivolumab 240 mg every 2 weeks or chemotherapy (topotecan or amrubicin) until progression or unacceptable toxicity. Primary endpoint was overall survival (OS).Overall, 284 patients were randomized to nivolumab and 285 to chemotherapy. Minimum follow-up was 15.8 months. No significant improvement in OS was seen with nivolumab versus chemotherapy [median OS, 7.5 versus 8.4 months; hazard ratio (HR), 0.86; 95% confidence interval (CI), 0.72-1.04; P = 0.11]. A survival benefit with nivolumab was suggested in patients with baseline lactate dehydrogenase ≤ upper limit of normal and in those without baseline liver metastases. OS (nivolumab versus chemotherapy) was similar in patients with programmed death-ligand 1 combined positive score ≥1% versus1%. Median progression-free survival was 1.4 versus 3.8 months (HR, 1.41; 95% CI, 1.18-1.69). Objective response rate was 13.7% versus 16.5% (odds ratio, 0.80; 95% CI, 0.50-1.27); median duration of response was 8.3 versus 4.5 months. Rates of grade 3 or 4 treatment-related adverse events were 13.8% versus 73.2%.Nivolumab did not improve survival versus chemotherapy in relapsed SCLC. No new safety signals were seen. In exploratory analyses, select baseline characteristics were associated with improved OS for nivolumab.
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- 2021
12. Pan-Cancer Efficacy of Vemurafenib in BRAFV600-Mutant Non-Melanoma Cancers
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Eric J. Sherman, Eli L. Diamond, Jean-Yves Blay, Todd Riehl, Vivek Subbiah, Gregory J. Riely, Bethany Pitcher, José Baselga, Funda Meric-Bernstam, Ian Chau, Jason Roszik, David M. Hyman, Noopur Raje, Igor Puzanov, Juergen Wolf, and A. Craig Lockhart
- Subjects
Adult ,Proto-Oncogene Proteins B-raf ,0301 basic medicine ,Lineage (genetic) ,Adolescent ,Colorectal cancer ,Article ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Neoplasms ,Glioma ,medicine ,Humans ,Vemurafenib ,neoplasms ,Protein Kinase Inhibitors ,Aged ,Aged, 80 and over ,Salivary gland ,business.industry ,Cancer ,Middle Aged ,medicine.disease ,Oncogene Addiction ,digestive system diseases ,Treatment Outcome ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,Mutation ,Cancer research ,Sarcoma ,business ,medicine.drug - Abstract
BRAF V600 mutations occur in a wide range of tumor types, and RAF inhibition has become standard in several of these cancers. Despite this progress, BRAFV600 mutations have historically been considered a clear demonstration of tumor lineage context–dependent oncogene addiction, based predominantly on the insensitivity to RAF inhibition in colorectal cancer. However, the true broader activity of RAF inhibition pan-cancer remains incompletely understood. To address this, we conducted a multicohort “basket” study of the BRAF inhibitor vemurafenib in non-melanoma BRAFV600 mutation–positive solid tumors. In total, 172 patients with 26 unique cancer types were treated, achieving an overall response rate of 33% and median duration of response of 13 months. Responses were observed in 13 unique cancer types, including historically treatment-refractory tumor types such as cholangiocarcinoma, sarcoma, glioma, neuroendocrine carcinoma, and salivary gland carcinomas. Collectively, these data demonstrate that single-agent BRAF inhibition has broader clinical activity than previously recognized. Significance: These data suggest that BRAFV600 mutations lead to oncogene addiction and are clinically actionable in a broad range of non-melanoma cancers, including tumor types in which RAF inhibition is not currently considered standard of care. See related commentary by Ribas and Lo, p. 640. This article is highlighted in the In This Issue feature, p. 627
- Published
- 2020
13. Nazartinib for treatment-naive EGFR-mutant non-small cell lung cancer: Results of a phase 2, single-arm, open-label study
- Author
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Daniel S.W. Tan, Sang-We Kim, Santiago Ponce Aix, Lecia V. Sequist, Egbert F. Smit, James C.H. Yang, Toyoaki Hida, Ryo Toyozawa, Enriqueta Felip, Juergen Wolf, Christian Grohé, Natasha B. Leighl, Gregory Riely, Xiaoming Cui, Mike Zou, Samson Ghebremariam, Leslie O'Sullivan-Djentuh, Riccardo Belli, Monica Giovannini, Dong-Wan Kim, and CCA - Cancer Treatment and quality of life
- Subjects
Adult ,Cancer Research ,Nicotine ,Lung Neoplasms ,Brain Neoplasms ,EGFR ,NSCLC ,ErbB Receptors ,Nazartinib ,Oncology ,Treatment-naive ,Carcinoma, Non-Small-Cell Lung ,Mutation ,Humans ,Benzimidazoles ,Protein Kinase Inhibitors ,Third-generation EGFR-TKI - Abstract
Introduction: Nazartinib, a novel third-generation EGFR-tyrosine kinase inhibitor, previously demonstrated antitumor activity and manageable safety in patients with EGFR-mutant advanced non−small cell lung cancer (NSCLC) who received ≤ 3 prior lines of systemic therapy. Herein, we report phase 2 efficacy and safety of first-line nazartinib. Methods: This single-arm, open-label, global study enrolled treatment-naive adult patients with stage IIIB/IV NSCLC harboring EGFR-activating mutations (eg, L858R and/or ex19del). Patients with neurologically stable and controlled brain metastases were also eligible. Patients received oral nazartinib 150 mg once daily. The primary endpoint was Blinded Independent Review Committee (BIRC)-assessed overall response rate (ORR) per RECIST v1.1. Results: Forty-five patients received ≥ 1 dose of nazartinib. The median follow-up time from enrollment to data cutoff (November 1, 2019) was 30 months (range: 25–34). The BIRC-assessed ORR was 69% (95% CI, 53–82). The median progression-free survival (PFS) was 18 months (95% CI, 15-not estimable [NE]). The median overall survival was NE. In patients with baseline brain metastases (n = 18), the ORR and median PFS (95% CIs) were 67% (41–87) and 17 months (11–21). Seventeen of 18 patients had brain metastases as non-target lesions; the CNS lesions were absent/normalized in 9 of 17 (53%). Only 2 of 27 patients without baseline brain metastases developed new brain metastases postbaseline. Most frequent adverse events (≥ 25%, any grade, all-causality) were diarrhea (47%), maculopapular rash (38%), pyrexia (29%), cough, and stomatitis (27% each). Conclusions: First-line nazartinib demonstrated promising efficacy, including clinically meaningful antitumor activity in the brain, and manageable safety in patients with EGFR-mutant NSCLC. Trial registration: ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT02108964.
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- 2022
14. ALK immunohistochemistry positive, FISH negative NSCLC is infrequent, but associated with impaired survival following treatment with crizotinib
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Egbert F. Smit, Buge Oz, Lukas Bubendorf, Stephen P. Finn, Lukas C. Heukamp, M. van den Heuvel, I. Marondel, A.O Grady, John R. Gosney, Anders Mellemgaard, Fabrice Duplaquet, Idris Bahce, Sayed M.S. Hashemi, Birgit Weynand, Xavier Durando, S.M.S. Samii, Patrick Pauwels, Pieter E. Postmus, Kim Monkhorst, Frédérique Penault-Llorca, S. Duin, Monika G. Looijen-Salamon, M.A. van der Drift, Ernst-Jan M. Speel, Wim Timens, Reinhard Buettner, N. Akyurek, Birgit I. Lissenberg-Witte, Erik Thunnissen, Birgit Guldhammer Skov, Ed Schuuring, Jens Benn Sørensen, Juergen Wolf, A.J. de Langen, Anne-Marie C. Dingemans, Guided Treatment in Optimal Selected Cancer Patients (GUTS), Groningen Research Institute for Asthma and COPD (GRIAC), Damage and Repair in Cancer Development and Cancer Treatment (DARE), Targeted Gynaecologic Oncology (TARGON), RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Pulmonologie, MUMC+: MA Med Staf Spec Longziekten (9), Pathologie, RS: GROW - R2 - Basic and Translational Cancer Biology, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - SSS/IREC/MORF - Pôle de Morphologie, UCL - (MGD) Service d'anatomie pathologique, UCL - (MGD) Service de pneumologie, Pathology, Epidemiology and Data Science, APH - Methodology, CCA - Cancer Treatment and quality of life, and Pulmonary medicine
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Male ,0301 basic medicine ,Oncology ,Cancer Research ,Lung Neoplasms ,INTERNATIONAL-ASSOCIATION ,Stress-related disorders Donders Center for Medical Neuroscience [Radboudumc 13] ,0302 clinical medicine ,alk ,Non-small cell lung cancer ,Carcinoma, Non-Small-Cell Lung ,hemic and lymphatic diseases ,Anaplastic lymphoma kinase ,Anaplastic Lymphoma Kinase ,Prospective Studies ,In Situ Hybridization, Fluorescence ,Gene Rearrangement ,fluorescence in situ hybridisation ,medicine.diagnostic_test ,treatment ,REARRANGEMENT ,Middle Aged ,OF-AMERICAN-PATHOLOGISTS ,Prognosis ,Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3] ,Immunohistochemistry ,PREVALENCE ,Survival Rate ,LUNG-CANCER PATIENTS ,Treatment Outcome ,030220 oncology & carcinogenesis ,immunohistochemistry ,%22">Fish ,Female ,Non small cell ,medicine.drug ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Rare cancers Radboud Institute for Molecular Life Sciences [Radboudumc 9] ,03 medical and health sciences ,MOLECULAR TESTING GUIDELINE ,All institutes and research themes of the Radboud University Medical Center ,Crizotinib ,Internal medicine ,Biopsy ,medicine ,Humans ,Protein Kinase Inhibitors ,non-small cell lung cancer ,business.industry ,ADENOCARCINOMA ,Treatment ,030104 developmental biology ,COPY NUMBER ,ALK ,KINASE INHIBITORS GUIDELINE ,Fluorescence in situ hybridisation ,Human medicine ,prognosis ,business ,Stage iv ,Fluorescence in situ hybridization ,IHC - Abstract
Objective: Metastasized non-small cell lung cancer (NSCLC) with an anaplastic lymphoma kinase (ALK) rearrangement is usually sensitive to a range of ALK-tyrosine kinase inhibitors. ALK-positive NSCLC have been identified in pivotal phase III trials with fluorescence in situ hybridization (ALK FISH +). These tumors are also expressing the fusion product (ALK immunohistochemistry (IHC) +). However, discrepant cases occur, including ALK IHC + FISH-. The aim of this study was to collect ALK IHC + cases and compare within this group response to crizotinib treatment of ALK FISH + cases with ALK FISH- cases.Materials and methods: In this European prospective multicenter research study patients with Stage IV ALK IHC + NSCLC treated with crizotinib were enrolled. Tumor slides were validated centrally for ALK IHC and ALK FISH.Results: Registration of 3523 ALK IHC tests revealed a prevalence of 2.7% (n = 94) ALK IHC + cases. Local ALK FISH analysis resulted in 48 concordant (ALK IHC + /FISH +) and 16 discordant (ALK IHC + /FISH-) cases. Central validation revealed 37 concordant and 7 discordant cases, 5 of which had follow-up. Validation was hampered by limited amount of tissue in biopsy samples. The PFS at 1 year for ALK concordant and discordant was 58% and 20%, respectively (HR = 2.4; 95% CI: 0.78-7.3; p = 0.11). Overall survival was significantly better for concordant cases than discordant cases after central validation (HR = 4.5; 95% CI = 1.2-15.9; p = 0.010.Conclusion: ALK IHC + FISH- NSCLC is infrequent and associated with a worse outcome on personalized treatment. A suitable predictive testing strategy may be to screen first with IHC and then confirm with FISH instead of considering ALK IHC equivalent to ALK FISH according to the current guidelines.
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- 2019
15. Capmatinib in MET exon 14-mutated, advanced NSCLC: Updated results from the GEOMETRY mono-1 study
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Rebecca S. Heist, Juergen Wolf, Andrea Chassot-Agostinho, Edward B. Garon, M. Carbini, Sylvie Le Mouhaer, Harry J.M. Groen, Anna Robeva, Daniel Shao-Weng Tan, Damage and Repair in Cancer Development and Cancer Treatment (DARE), and Guided Treatment in Optimal Selected Cancer Patients (GUTS)
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Cancer Research ,Exon ,Capmatinib ,Oncology ,business.industry ,Cancer research ,Medicine ,business ,MET Exon 14 Skipping Mutation - Abstract
9020 Background: Capmatinib, a selective MET inhibitor, is approved in the USA and Japan for the treatment of patients (pts) with MET exon 14 skipping mutation ( METex14) advanced non-small-cell lung cancer (NSCLC) based on the multi-cohort phase II GEOMETRY mono-1 study. This is the first report on expansion Cohort 7 in first line (1L) METex14 NSCLC pts, with updates to previously reported results (Wolf et al, NEJM 2020) for METex14 pts. Methods: In GEOMETRY mono-1, pts were assigned to cohorts based on previous lines of therapy and MET status ( METex14 or MET amplification). This efficacy analysis includes patients with METex14 NSCLC who were treatment-naive (Cohort 5b and 7) and those who had previously received 1L or 2L of therapy (expansion Cohort 6 and Cohort 4) for their advanced disease (data cutoff: Sep 18, 2020). Evaluated outcomes included overall response rate (ORR), duration of response (DOR), and progression-free survival (PFS), all by BIRC; and overall survival (OS). The safety analysis includes all patients enrolled. Results: In total, 160 pts with METex14 who received capmatinib 400 mg BID were analyzed. ORR of 65.6% (95% CI 46.8-81.4) for the treatment-naive expansion Cohort 7 was in line with that previously reported for Cohort 5b (Table). Though Cohort 7 data are still immature, median PFS was 10.8 mo (95% CI 6.87-not estimable [NE]). Mature median OS was 20.8 mo (95% CI 12.4-NE) in Cohort 5b and 13.6 mo (95% CI 8.6-22.2) in Cohort 4. Median OS for Cohorts 6 and 7 and DOR for Cohort 7 are not yet reached. The safety profile remained unchanged across all study cohorts (N = 373): 98.4% of pts reported AEs (68.6% Grade [G] 3/4) regardless of causality and 16.1% reported AEs leading to discontinuation (10.5% G3/4). The most common AEs (≥20% all G) were peripheral edema (54.2%), nausea (45.0%), vomiting (28.2%), increased blood creatinine (26.5%), dyspnea (23.3%), fatigue (22.3%), and decreased appetite (21.2%). Conclusions: Results of Cohort 7 confirm those previously reported for Cohort 5b showing higher efficacy of capmatinib when used as 1L in METex14 NSCLC pts. A clinically meaningful median OS of 20.8 mo in 1L (Cohort 5b) and of 13.6 mo in relapse (Cohort 4) was also observed and, together with the continued manageable toxicity profile, the data support capmatinib as a valuable targeted treatment option for METex14 NSCLC pts. Clinical trial information: NCT02414139. [Table: see text]
- Published
- 2021
16. Das nationale Netzwerk Genomische Medizin (nNGM)
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A. Kron, Juergen Wolf, Reinhard Büttner, and Nationales Netzwerk Genomische Medizin
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0301 basic medicine ,Gynecology ,03 medical and health sciences ,medicine.medical_specialty ,030104 developmental biology ,0302 clinical medicine ,Health care quality assurance ,030220 oncology & carcinogenesis ,Political science ,medicine ,Pathology and Forensic Medicine - Abstract
Seit 2012 versorgt das Netzwerk Genomische Medizin (NGM) eine grose Zahl von Lungenkrebspatienten mit einer zentralen molekularen Multiplexdiagnostik im Institut fur Pathologie des Universitatsklinikums Koln. Daruber hinaus interpretiert die Netzwerkzentrale in Koln die Befunde in enger interdisziplinarer Abstimmung zwischen Pathologen und Onkologen, informiert uber innovative Behandlungsmoglichkeiten und evaluiert die personalisierten Therapien mithilfe der zentralen Datenbank. Im Rahmen einer ihrer grosten Einzelfordermasnahmen in 2018 hat die Deutsche Krebshilfe (DKH) dieses interdisziplinare und intersektorale Versorgungsmodell auf alle zum Zeitpunkt der Erstantragsstellung bestehenden onkologischen Spitzenzentren ausgerollt. Darstellung der Versorgungsrealitat im nationalen Netzwerk Genomische Medizin (nNGM) mit seinen Kernelementen und Akteuren (Netzwerkzentren und intersektoralen klinischen Netzwerkpartnern). Diese Arbeit basiert auf eigenen Erfahrungen in NGM und nNGM und beinhaltet eine Zusammenfassung der aktuell geltenden Richtlinien zur Kostenerstattung sowie eine Ubersicht uber die Versorgungslandschaft im Bereich der molekularpathologischen Diagnostik. Der Fokus von nNGM liegt auf der Implementierung innovativster Diagnostik und Therapie in die Breite der Versorgung. Dies soll gewahrleistet werden durch fortlaufende Weiterentwicklung molekularpathologischer Diagnostik innerhalb der Netzwerkzentren, interdisziplinare Beratung der regionalen Netzwerkpartner, innovatives Angebot an klinischen Studien, Erarbeitung von Modellen zur Kostenerstattung und zentrale Evaluation. Ein besonderer Schwerpunkt liegt auf dem Ausbau regionaler Netzwerke, um die betroffenen Lungenkrebspatienten moglichst dezentral (heimatnah) durch die klinischen Netzwerkpartner zu behandeln. Fur eine erfolgreiche Implementierung der molekularpathologischen Multiplexdiagnostik und der daraus resultierenden Therapie sind interdisziplinare Teams ausschlaggebend. nNGM behebt ein Defizit bei der Versorgung von Lungenkrebspatienten und soll zukunftig um weitere Netzwerkzentren erweitert werden.
- Published
- 2019
17. Early Palliative Care: Pro, but Please Be Precise!
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Michael von Bergwelt-Baildon, Jan Gärtner, Marion Daun, Michael Hallek, and Juergen Wolf
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Cancer Research ,Palliative care ,Health professionals ,Symptom management ,business.industry ,Communication ,Palliative Care ,Fear ,Hematology ,Disease ,Symptom assessment ,Advance Care Planning ,03 medical and health sciences ,Identification (information) ,0302 clinical medicine ,Oncology ,Nursing ,Neoplasms ,030220 oncology & carcinogenesis ,Practice Guidelines as Topic ,Humans ,Medicine ,030212 general & internal medicine ,Communication skills ,business - Abstract
Background: By definition, palliative care (PC) is applicable already in early stages of incurable and life-threatening diseases, in conjunction with therapies that are intended to prolong life, such as for example chemo- or radiotherapy. Many patients suffer from distressing symptoms or problems in early phases of such illness. Therefore, it is not a question of “if” PC should be integrated early into oncology, but “how.” General PC is defined as an approach that should be delivered by healthcare professionals regardless of their discipline. This is often referred to as “general” or “primary” PC. For this, routine symptom assessment, expertise concerning basic symptom management, and communication skills are basic requirements. Communication skills include the willingness to engage in discussions concerning patients' fears, worries and end-of-life issues without the fear of destroying hope. Specialist PC is provided by specialist teams regardless of the patients' disease, be it cancer or non-cancer. Such teams should be integrated in the care of PC patients depending on the availability of these services and the patients' needs. Key messages: “Early PC” must not be used synonymously with “early specialist PC” because much of the PC is delivered as basic oncology PC. For the integration of specialist PC, the identification of triggers is warranted in different institutions to facilitate a meaningful and effective cooperation. Such cooperations should be based on patients' needs, but must also account for questions of availability and resources.
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- 2019
18. Abstract CT558: Capmatinib vs docetaxel as second- or third-line therapy in patients with locally advanced or metastatic METex14-mutated NSCLC: The GeoMETry-III trial
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Pierre Jean Souquet, Sang-We Kim, Johan F. Vansteenkiste, Anna Robeva, Aline Jary, Sabine Glaser, Alejandro Yovine, and Juergen Wolf
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Cancer Research ,Oncology - Abstract
Background: MET dysregulation is a poor prognostic factor in advanced non-small cell lung cancer (NSCLC). MET exon 14 skipping (METex14) mutations occur in ~3% of patients with NSCLC. There is limited evidence of the efficacy of standard therapies, such as chemotherapy or immunotherapy, in patients with METex14-mutated advanced NSCLC. Capmatinib, a MET inhibitor (METi), is approved for the treatment of adult patients with metastatic METex14-mutated NSCLC, based on the results of the phase 2 GEOMETRY mono-1 study. Results (data cutoff: September 18, 2020) of this study in patients with METex14-mutated NSCLC treated with capmatinib showed an overall response rate (ORR) of 66.7% in first line (N=60), 51.6% in second line (N=31) and 40.6% in second- or third-line (2/3L; N=69). GeoMETry-III (NCT04427072) is a multicenter, open-label, randomized, controlled, global, phase 3 trial that is further evaluating the efficacy and safety of capmatinib vs docetaxel in the 2/3L setting in patients with METex14-mutated NSCLC. Methods: This study began enrollment in September 2020 and is currently recruiting adult patients with EGFR wild-type, ALK-negative, stage IIIB/IIIC/IV METex14-mutated NSCLC, who have progressed on 1 or 2 prior lines of systemic therapy for advanced/metastatic disease and are candidates for single-agent docetaxel. Other eligibility criteria include ≥1 measurable lesion per the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), an Eastern Cooperative Oncology Group performance status of ≤1 and no prior treatment with any METi or hepatocyte growth factor-targeting therapies. Patients with neurologically unstable, symptomatic central nervous system (CNS) metastases or those requiring increasing doses of steroids ≤2 weeks prior to study entry to manage CNS symptoms are excluded. Around 90 patients will be randomized 2:1 to receive either oral capmatinib 400 mg twice daily or intravenous docetaxel 75 mg/m2 every 21 days. Randomization is stratified by number of prior lines (1 or 2) of systemic therapy. Patients meeting protocol-specified eligibility criteria can cross over from the docetaxel to the capmatinib arm after blinded independent review committee (BIRC)-confirmed progressive disease as per RECIST 1.1.The primary endpoint is progression-free survival (PFS) by BIRC per RECIST 1.1. The key secondary endpoint is ORR by BIRC per RECIST 1.1. Other secondary endpoints include investigator-assessed ORR and PFS; duration of response, time to response and disease control rate (DCR) by BIRC and investigator; overall survival; safety; pharmacokinetics; patient-reported outcomes; overall intracranial response rate, intracranial DCR, duration of- and time to- intracranial response by BIRC per the Response Assessment in Neuro-Oncology Brain Metastases criteria in patients with baseline CNS lesions. Citation Format: Pierre Jean Souquet, Sang-We Kim, Johan F. Vansteenkiste, Anna Robeva, Aline Jary, Sabine Glaser, Alejandro Yovine, Juergen Wolf. Capmatinib vs docetaxel as second- or third-line therapy in patients with locally advanced or metastatic METex14-mutated NSCLC: The GeoMETry-III trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT558.
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- 2022
19. Abstract CT008: Long-term outcomes with sotorasib in pretreated KRASp.G12C-mutated NSCLC: 2-year analysis of CodeBreaK100
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Grace K. Dy, Ramaswamy Govindan, Vamsidhar Velcheti, Gerald S. Falchook, Antoine Italiano, Juergen Wolf, Adrian G. Sacher, Toshiaki Takahashi, Suresh S. Ramalingam, Christophe Dooms, Dong-Wan Kim, Alfredo Addeo, Jayesh Desai, Martin Schuler, Pascale Tomasini, Qui Tran, Simon Jones, Agnes Ang, Abraham Anderson, Antreas A. Hindoyan, David S. Hong, and Bob T. Li
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Cancer Research ,Oncology - Abstract
Introduction: Sotorasib, a first-in-class KRASG12C inhibitor, has been FDA-approved for adults with KRAS p.G12C-mutated locally advanced or metastatic NSCLC who received prior systemic therapies based on the Phase 1/2 global, single-arm CodeBreaK100 trial. We will report the longest follow-up for a KRASG12C inhibitor, including 2-year survival, safety, and genomic profiles associated with durable clinical benefit. Methods: Sotorasib was administered orally at 960 mg once daily to patients who progressed on prior therapies and had KRAS p.G12C-mutated locally advanced, metastatic NSCLC. Primary endpoint was objective response rate (ORR) assessed by central review. Key secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. In an exploratory analysis, baseline tumor tissue and/or plasma samples were collected and analyzed for genomic alterations. Tumor samples were analyzed for PD-L1 levels to evaluate correlates with prolonged tumor response, defined as patients with PFS ≥ 12 months, in comparison with those with PFS ≤ 3 months. Results: In the first analysis of the combined Phase 1 and Phase 2 study (N=174), the median number of prior lines of therapy was 2.0 (range 1-4+). 90.2% received prior anti-PD1 or anti PD-L1 treatment; 82.8% received both prior platinum-based chemotherapy and anti-PD1/PD-L1. Updated ORR by central review was 40.7% (95% CI: 33.2, 48.4) and median DOR was 12.3 months (7.1, 14.6). Median PFS and OS was 6.3 months (95% CI: 5.3, 8.2) and 12.5 months (10.0, 17.8). One and two-year OS was 50.8% and 30.3%. Sotorasib was well-tolerated in the long-term with mild and manageable toxicities, and no new safety signals emerged. Prolonged tumor response was observed across PD-L1 expression, including in tumors with low PDL-1 expression and STK11 co-mutation that may derive less benefit from immunotherapy. Conclusions: In the longest follow-up of any KRASG12C inhibitor, sotorasib continued to demonstrate a favorable safety profile and durable efficacy, including a 2-year OS observed in 30% of patients. Current analyses continue to support long-term clinical benefit across subgroups in patients with KRAS p.G12C-mutated NSCLC, and additional biomarker data will be presented. Citation Format: Grace K. Dy, Ramaswamy Govindan, Vamsidhar Velcheti, Gerald S. Falchook, Antoine Italiano, Juergen Wolf, Adrian G. Sacher, Toshiaki Takahashi, Suresh S. Ramalingam, Christophe Dooms, Dong-Wan Kim, Alfredo Addeo, Jayesh Desai, Martin Schuler, Pascale Tomasini, Qui Tran, Simon Jones, Agnes Ang, Abraham Anderson, Antreas A. Hindoyan, David S. Hong, Bob T. Li. Long-term outcomes with sotorasib in pretreated KRASp.G12C-mutated NSCLC: 2-year analysis of CodeBreaK100 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT008.
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- 2022
20. Largest evaluation of acquired resistance to sotorasib in KRAS p.G12C-mutated non–small cell lung cancer (NSCLC) and colorectal cancer (CRC): Plasma biomarker analysis of CodeBreaK100
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Bob T. Li, Vamsidhar Velcheti, Timothy Jay Price, David S. Hong, Marwan Fakih, Dong-Wan Kim, Gerald Steven Falchook, Jean-Pierre Delord, Grace K. Dy, Suresh S. Ramalingam, John H Strickler, Takayasu Kurata, Juergen Wolf, Adrian G. Sacher, Alfredo Addeo, Hans Prenen, Antreas Hindoyan, Abraham Anderson, Agnes Ang, and Ferdinandos Skoulidis
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Cancer Research ,Oncology - Abstract
102 Background: Sotorasib, a specific, irreversible KRASG12C inhibitor, has been approved in multiple countries for adults with KRAS p.G12C-mutated locally advanced or metastatic NSCLC who received prior systemic therapy based on the global phase 1/2 CodeBreaK100 trial. Here we describe putative mechanisms of acquired resistance to sotorasib from the largest single dataset evaluated to-date. Methods: Patients with advanced KRAS p.G12C-mutated NSCLC or CRC from the CodeBreaK100 Ph1/2 trial who received sotorasib monotherapy at 960 mg once daily were analyzed for efficacy. Primary endpoint was objective response rate (ORR) assessed by central review. To investigate biomarkers of resistance to sotorasib, an exploratory endpoint was defined to examine acquired genomic alterations at disease progression. Plasma samples collected at baseline and progression were analyzed for genomic alterations with the 23-gene Resolution Bioscience ctDx Lung test for NSCLC and the 74-gene Guardant 360 ctDNA test for CRC. Acquired genomic alterations were defined by their absence at baseline and presence at progression. Results: In 174 pts with NSCLC and 91 pts with CRC-treated with sotorasib, the ORR were 41% and 12% respectively. Median progression-free survival and median overall survival were 6.3 months (mos) and 12.5 mos for NSCLC pts and 4.2 mos and 13.4 mos for CRC pts (median follow-up: 22.5 mos NSCLC; 12.5 mos CRC). A total of 67 NSCLC pts and 45 CRC pts had a plasma sample sequenced both at baseline and at progression. At least one new acquired genomic alteration at progression was detected in 19 (28%) NSCLC pts and in 33 (73%) CRC pts (Table). The acquired genomic alterations were heterogeneous in both NSCLC and CRC, with variants detected across multiple genes and pathways. The most prevalent putative pathway of resistance in both NSCLC and CRC was the receptor tyrosine kinase (RTK) pathway. Secondary RAS alterations occurred more frequently in CRC versus NSCLC pts (16% vs. 3%). Conclusions: Based on the largest descriptive dataset to-date, diverse mechanisms of acquired resistance occur in KRAS p.G12C-mutated NSCLC and CRC pts treated with sotorasib. New RTK pathway alterations frequently emerged at progression, highlighting the potential role for combining sotorasib with upstream inhibitors of RTK, such as SHP2 or EGFR inhibitors. Serial plasma DNA analysis revealed acquired resistance patterns that support the development of KRASG12C inhibitor combination therapies. Clinical trial information: NCT03600883. [Table: see text]
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- 2022
21. Screening of FGFR patients for FGFR directed clinical trials in Network Genomic Medicine (NGM): Real-world data
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Heather Scharpenseel, Florian Malchers, Inken Terjung, Axel Hillmer, Sabine Merkelbach-Bruse, Andreas H. Scheel, Janna Siemanowski, Matthias Scheffler, Richard Riedel, Anna Eisert, Sebastian Yves Friedrich Michels, Rieke Nila Fischer, Jan-Philip Weber, Theresa Westphal, Anna Kron, Juliane Sueptitz, Roman K. Thomas, Reinhard Buettner, Juergen Wolf, and Lucia Nogova
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Cancer Research ,Oncology - Abstract
e21013 Background: The fibroblast growth factor receptor (FGFR) 1-4 genes show a heterogenic landscape of alterations in non-small cell lung cancer (NSCLC) whereas only a small amount is yet considered to have oncogenic potential. The frequency of activating FGFR alterations is low, counting for approximately 2% of NSCLC. We have screened NSCLC patients (pts) for FGFR translocations/mutations within NGM and analysed them on FGFR alteration frequency, patient characteristics and outcome. Methods: From 04/2019 to 01/2020 we screened 472 squamous NSCLC for FGFR gene alterations and from 02/2020 to 12/2021 an additional 5286 patients including all NSCLC cases. Of these 5286 pts, 1097 pts were analysed for FGFR fusions. We used DNA-NGS for FGFR-mutations and RNA-NGS for FGFR–translocations. Activating mutations were defined according to the publicly available molecular data bases and published data. Results: Within the cohort of 5758 NSCLC patients, we found 316 (5.5%) patients with FGFR alterations. Sixty-six (20.9% of FGFR, 1.1% of NSCLC) patients had alterations classified as activating, of whom 39 had FGFR point mutations and 27 FGFR translocations. Concerning the patients with activating alterations, they had UICC stage III or IV at time of diagnosis; 22 were females; 58 patients had squamous cell carcinoma, 6 patients had adenocarcinoma and 2 had large cell neuroendocrine carcinoma. Fifty-three patients (80.3%) with activating FGFR alteration had a co-mutation: TP53 (inactivating) co-mutation was seen in 41 cases (62.1%) and 19 cases had either PTEN (7 pts), KRAS (4), EGFR (3), PIK3CA (2), ROS1 (1), ALK (1) or BRAF (1) mutations. Ten patients were included in a FGFR-targeted trial. Sixty patients were available for follow-up. The median overall survival (mOS) was 21.4 month (95%CI: 16.8–25.9) for all patients with activating FGFR alteration, whereas mOS was 18.5 month (95%CI: 13.2-23.9) for FGFR mutation and 25.3 months (95%CI: 17.8-32.9) for FGFR fusions. Conclusions: FGFR 1-4 gene alterations are rare. Large molecular and clinical networks are necessary to identify these pts. Prognostic factors of FGFR patients are currently not defined. Further assessments on molecular and clinical features in FGFR altered NSCLC are needed to identify sensitivity to FGFR inhibition. Clinical trials with specific FGFR inhibitors are ongoing.
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- 2022
22. Tumor agnostic efficacy of selpercatinib in patients with RET fusion+ solid tumors: A global, multicenter, registrational trial update (LIBRETTO-001)
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Vivek Subbiah, Juergen Wolf, Bhavana Konda, Hyunseok Kang, Alexander I. Spira, Jared Weiss, Masayuki Takeda, Yuichiro Ohe, Saad A. Khan, Kadoaki Ohashi, Victoria Soldatenkova, Sylwia Szymczak, Loretta Sullivan, Jennifer Wright, and Alexander E. Drilon
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Cancer Research ,Oncology - Abstract
3094 Background: Selpercatinib, a first-in-class highly selective and potent RET kinase inhibitor, is approved in multiple countries for the treatment of lung and thyroid cancer with RET fusions and medullary thyroid cancer with RET mutations. We provide an efficacy and safety update with more patients (pts) and longer follow-up (data cut-off: 24Sep2021) in RET fusion+ solid tumors with histologies other than lung/thyroid. Methods: The phase 1/2 LIBRETTO-001 trial (NCT03157128) enrolled pts with locally advanced/metastatic RET fusion+ solid tumors. Following dose escalation, pts received the recommended dose of 160 mg orally twice daily. The efficacy analysis set consisted of pts enrolled ≥6 months (mo) prior to the cut-off date. If a pt achieved response, an additional ≥6 mo follow-up from the initial response was required. There was no additional follow-up required for non-responders. Response was assessed per RECIST 1.1. Primary endpoint was objective response rate (ORR) by independent review committee (IRC). Secondary endpoints included ORR by investigator (INV), duration of response (DoR), progression-free survival (PFS), time to response (TTR), and safety. Results: Forty-five pts with 14 unique RET fusion+ tumor types received ≥1 dose of selpercatinib: 12 pancreatic, 10 colon, 4 salivary, 3 unknown primary, 3 sarcoma, 2 each of breast, carcinoma of the skin, xanthogranuloma, and cholangiocarcinoma, and 1 each of lung carcinoid, rectal neuroendocrine, small intestine, ovarian, and pulmonary carcinosarcoma. Median age was 53 years (range 21-85). Forty-one pts received prior systemic therapy (median prior lines: 2, range 0-9); 31% received ≥3 lines. In 41 efficacy-evaluable pts, confirmed ORR by IRC was 44% (18/41, 95% CI: 29-60). Clinical benefit was observed in 63% (26/41) of pts: 2 complete responses (breast, small intestine), 16 partial responses, and stable disease ≥16 weeks in 8 pts by IRC. Responses were observed across a variety of fusion partners. Median TTR was 1.9 mo by IRC. Median DoR was 24.5 mo (95% CI: 9.2-NE) with 50% (9/18) of responses ongoing at a median follow-up of 14.9 mo by IRC. Median PFS by IRC was 13.2 mo (95% CI: 7.4-26.2), with 34.1% alive and progression-free at a median follow-up of 16.4 mo. No new safety signals were identified in this cohort compared to broader safety database. Three grade 5 AEs were observed (unrelated to treatment by INV), and 4 pts discontinued treatment due to AEs (1 deemed related to treatment by INV). Conclusions: Selpercatinib continued to demonstrate durable antitumor activity in pts with RET fusion+ cancers across multiple tumor types. No new safety signals were identified. These results emphasize the importance of comprehensive genomic profiling to identify actionable oncogenic drivers, including RET fusions. The LIBRETTO-001 study continues to enroll pts. Clinical trial information: NCT03157128.
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- 2022
23. Crizotinib in ROS1-rearranged lung cancer (EUCROSS): Updated overall survival
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Sebastian Yves Friedrich Michels, Jeremy Franklin, Bartomeu Massuti, Martin Sebastian, Enriqueta Felip, Christian Grohé, Delvys Rodriguez-Abreu, Helge Bischoff, Enric Carcereny, Jesús Corral, Amelia Insa, Martin Reck, Sacha Rothschild, Mariano Provencio, Matthias Scheffler, Martin Hellmich, Lucia Nogova, Reinhard Büttner, Rafael Rosell, and Juergen Wolf
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Cancer Research ,Oncology - Abstract
9078 Background: ROS1 rearrangements are found in approximately 1% of non-small cell lung cancer (NSCLC) patients. Prospective clinical trials showed high efficacy of crizotinib in this molecular subset. Lately, we reported an overall response rate (ORR) of 70% and a median progression-free survival (PFS) of 19.4 months for patients treated within the EUCROSS trial (Michels et al. Clin Oncol, 37(15_suppl):9066-9066, 2019). Here we present an updated analysis of the overall survival. Methods: EUCROSS is a European multi-centre, single arm phase 2 trial (Clinicaltrial.gov identifier: NCT02183870). Key eligibility criteria were ≥18 years of age, advanced/metastatic lung cancer, centrally confirmed ROS1-rearranged (fluorescence-in situ hybridisation) and no or stable brain metastases at baseline. Crizotinib was given at a dose of 250 mg twice daily. Primary endpoint of the trial was investigator-assessed ORR in the response-evaluable population (Response Evaluation Criteria in Solid Tumors, version 1.1), with secondary endpoints of PFS and overall survival (OS). Results: Of the 34 patients who received at least one dose of crizotinib (intention-to-treat population, ITT), 30 were included the primary efficacy analysis set (PAS). After a median follow-up of 55.9 months, 13 (43%) patients in the PAS and 15 (44%) in the ITT had died. Median OS was not reached in either group (95% CI, 17.1-NR and 20.3-NR, respectively). OS was negatively correlated with the presence of brain metastases (Log-rank p = 0.1805) and TP53 mutations (Log-rank p = 0.015). Detailed listings of the survival rates are depicted in Table. No new safety signals were observed. Owing to the approval of crizotinib by the European Medicines Agency, all patients who were still on treatment by January 24th 2018 (n=8), were prescribed crizotinib outside the trial. Conclusions: Updated OS highlights the efficacy of crizotinib in patients with ROS1-rearranged lung cancer. Patients with co-occurring TP53 mutations or brain metastases had worse outcomes and represent challenging populations. Clinical trial information: NCT02183870. [Table: see text]
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- 2022
24. A first-in-human phase 1 study of the next-generation RET inhibitor, LOXO-260, in RET inhibitor refractory patients with RET-altered cancers (trial in progress)
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Nathan A. Pennell, Lori J. Wirth, Justin F. Gainor, Julia K Rotow, Melissa Lynne Johnson, Todd Michael Bauer, Matthias Kroiss, Vineeth Sukrithan, Hyunseok Kang, Francis P. Worden, Christine M. Bestvina, Julien Hadoux, Philippe Alexandre Cassier, Antoine Italiano, Juergen Wolf, Marcia S. Brose, Emin Avsar, Michael D. Axelson, Vivek Subbiah, and Alexander E. Drilon
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Cancer Research ,Oncology - Abstract
TPS8595 Background: RET fusions are found in 1-2% of lung adenocarcinomas and 10-20% of papillary thyroid carcinomas. Activating RET mutations occur in 50-60% of medullary thyroid cancers (MTCs). Selpercatinib was the first selective RET inhibitor approved by the FDA and is indicated for patients (pts) with RET fusion-positive NSCLC and thyroid cancer, and RET mutant MTC. Despite marked and durable activity, acquired resistance can eventually develop through a variety of mechanisms. These include acquisition of RET G810X mutations at the solvent front of the ATP pocket. LOXO-260 is a highly potent and selective inhibitor of RET designed to have activity against both solvent front and gatekeeper mutations, expressed alone or together, while maintaining potency against RET fusions or mutations (Kolakowski GR. et al. 2021 Cancer Research 81 (13 Suppl) 1464). Methods: LOXO-NGR-21001 is a global, open-label, first-in-human phase 1 study of LOXO-260 in pts with RET fusion-positive advanced solid tumors and RET mutant MTC who received a prior selective RET inhibitor. Phase 1a dose escalation will utilize a modified i3+3 design, allowing for pt backfill to previously cleared dose levels. Phase 1b dose expansion will evaluate LOXO-260 in specific expansion cohorts: RET fusion-positive NSCLC or thyroid cancers and RET mutant MTC. The primary objectives in dose escalation are to determine the MTD/RP2D and safety of LOXO-260. Key secondary objectives include characterization of PK and preliminary antitumor activity of LOXO-260 per RECIST v1.1. The primary objective of dose expansion is to assess the antitumor activity of LOXO-260 based on investigator-assessed overall response rate (ORR). Key secondary objectives are to characterize the PK and antitumor activity of LOXO-260 based on progression-free survival (PFS), time to response (TTR), and duration of response (DOR). Eligible pts must have received a prior selective RET inhibitor, have a documented RET fusion or RET mutation and a diagnosis of locally advanced, unresectable and/or metastatic cancer per disease-specific criteria, and must have progressed or be intolerant to standard therapies or must have refused such a therapy. Pts must be ≥18 years old and have an ECOG PS of 0-2. Key exclusion criteria include presence of serious cardiac conditions, interstitial lung disease, symptomatic CNS metastases, or carcinomatous meningitis. Clinical trial information: NCT05241834.
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- 2022
25. Efficacy and safety of capmatinib plus pembrolizumab in treatment (tx)-naïve patients with advanced non–small cell lung cancer (NSCLC) with high tumor PD-L1 expression: Results of a randomized, open-label, multicenter, phase 2 study
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Tony S. K. Mok, Diego Luigi Cortinovis, Margarita Majem, Melissa Lynne Johnson, Feby Ingriani Mardjuadi, Xuan Zhao, Sagar Vidya Siripurapu, Zhiqiang Jiang, and Juergen Wolf
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Cancer Research ,Oncology - Abstract
9118 Background: Capmatinib is a selective MET inhibitor approved for patients (pts) with metastatic NSCLC harboring MET exon 14 skipping mutation. Pembrolizumab (pembro) is a programmed death protein-1 (PD-1) inhibitor approved as monotherapy for pts with advanced NSCLC expressing PD-ligand 1 (PD-L1). Preclinical studies have shown that capmatinib enhances T cell mediated antitumor response in mice treated with PD-1 inhibitors. Combining capmatinib with pembro may be beneficial in pts with advanced NSCLC expressing high tumor PD-L1. Methods: Herein we evaluated the efficacy and safety of capmatinib plus pembro (combo) versus pembro alone in tx-naïve pts with advanced MET-unselected NSCLC expressing PD-L1 with tumor proportion score (TPS) ≥50%, and no ALK or EGFR tumor aberrations. Pts received pembro 200 mg IV q3w in the pembro alone arm or with capmatinib 400 mg orally BID in the combo arm. The primary endpoint was investigator-assessed progression-free survival (PFS) using RECIST v1.1. Secondary endpoints included overall response rate (ORR), disease control rate (DCR), pharmacokinetics and safety. Results: As of the data cut off (DCO) of 28 Feb 2021, 76 pts were randomized 2:1 to the combo arm (n = 51) or pembro alone arm (n = 25). Baseline demographics and disease status were mostly comparable across study arms. At this interim analysis, PFS data were not mature. Median PFS (95% CI) was 6.3 (3.2, not evaluable [NE]) months in the combo arm and 4.3 (2.3, NE) months in the pembro alone arm. The ORR (95% CI) was 15.7% (7.0%, 28.6%) and 28.0% (12.1%, 49.4%) in the combo and pembro alone arms, respectively. The DCR (95% CI) was comparable across study arms; combo: 56.9% (42.2%, 70.7%) and pembro alone: 56.0% (34.9%, 75.6%). In the combo arm, capmatinib exposure (Cmax: 3580 ng/mL [n = 7] and AUCtau: 19700 hr*ng/mL [n = 2]) was consistent with data from previous studies. Tx-related grade (GR) ≥3 adverse events (AEs) were more common in the combo (37.3%) vs pembro alone arm (16%). Tx-related AEs occurring in ≥10% of pts are shown in the Table. Tx discontinuation and dose adjustment/interruptions were more common in the combo (27.5% and 52.9%) vs pembro alone arm (16% and 16%). Capmatinib was stopped prematurely in the combo arm, and at DCO, 32 (62.7%) pts in the combo arm and 18 (72%) pts in the pembro alone arm were receiving pembro monotherapy. Conclusions: Combination tx with capmatinib and pembro was not well tolerated and did not improve antitumor activity in tx-naïve pts with advanced NSCLC with PD-L1 TPS ≥50%. Clinical trial information: NCT04139317. [Table: see text]
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- 2022
26. Metastatic patterns plus clinical and molecular characteristics of ROS1 aberrations in non-small cell lung cancer patients without rearrangements
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Moritz Glaser, Cornelia von Levetzow, Sebastian Yves Friedrich Michels, Lucia Nogova, Marianna Katzenmeier, Claudia Wompner, Jaqueline Schmitz, Elisabeth Bitter, Inken Terjung, Elke Passmann, Diana Schaufler, Anna Eisert, Rieke Nila Fischer, Richard Riedel, Jan-Phillip Weber, Sabine Hahne, Sabine Merkelbach-Bruse, Reinhard Büttner, Juergen Wolf, and Matthias Scheffler
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Cancer Research ,Oncology - Abstract
e21117 Background: Fusions in the ROS1 proto-oncogene are among the best treatable genetic aberrations in Non-small cell lung cancer (NSCLC). Besides the occurrence of solvent-front mutations (SFM) in acquired resistance to targeted therapy, little is known about ROS1 aberrations other than fusions. We analyzed molecular and clinical characteristics and metastatic patterns of ROS1 mutations in NSCLC patients without activating ROS1 fusions or SFMs. Methods: Next-generation sequencing (NGS) was performed on tissue samples from NSCLC patients within the National Network Genomic Medicine (nNGM). Patients with activating ROS1 fusions detected by fluorescence in-situ hybridization (FISH) were excluded. Staging and restaging procedures were performed following local standards from each partner. We analyzed the mutations’ characteristics, co-occurring mutations and metastatic patterns. Results: Of 8072 patients analyzed by NGS between 2018 and 2021, 118 (1.5%) patients harbored ROS1 mutations. Most patients were male (76.3%) and had adenocarcinoma histology (57.6%). The median age at diagnosis amounted to 68 years. Nearly all of the patients (96.5%) had a smoking history, amassing 40 pack-years on average. Besides TP53 mutations (61.0%), KRAS (25.4%), EGFR (7.6%), PIK3CA and FGFR1-4 mutations (5.9% each) co-occurred most frequently. In 12 (10.2%) patients, ROS1 mutation was the only detected aberration. The majority (59.3%) of patients had UICC stage IV whereby 27.2% of patients featured Stage III; about 7% fall upon stage I and II. The metastatic pattern of all stage IV patients shows that 22.9% of metastasis is allotted to cerebral, 12.5% to lung, 16.7% to subdiaphragmatic, 14.9% to bone and 6.3% to skin metastasis. Thereby, the patients’ subgroup with mutually exclusive ROS1 mutations (10.2%) resembles this trend: about a half of these patients had UICC stage IV, too, and the metastasis distribution featured similar characteristics. Conclusions: The cohort contrasts the clinical characteristics of patients with ROS1 fusion regarding sex, age, and histology. This evidence implies a basic clinical impact exerted by this molecular subtype. We warrant further research on the detected mutations to characterize the biological impact and the potential to act as a drug target.
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- 2022
27. Strategien zur Überwindung der erworbenen EGFR-TKI-Resistenz durch T790M spezifische Substanzen am Beispiel von Osimertinib
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M. Kimmich, R. Pirker, Frank Griesinger, O. Gautschi, Martin Sebastian, Juergen Wolf, A. Lüers, C. Schulz, W. Brugger, Rainer Wiewrodt, Martin Früh, S. Radke, and B. Deschler-Baier
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0301 basic medicine ,Pulmonary and Respiratory Medicine ,Gynecology ,03 medical and health sciences ,medicine.medical_specialty ,030104 developmental biology ,0302 clinical medicine ,business.industry ,030220 oncology & carcinogenesis ,Medicine ,business - Abstract
Zusammenfassung Die Resistenzbildung gegenüber der 1. und 2. Generation von Tyrosinkinase-Inhibitoren (TKIs) des epidermalen Wachstumsfaktors (EGFR) stellt bei der Behandlung von Patienten mit nicht kleinzelligem Lungenkarzinom, die eine aktivierende Mutation im EGFR aufweisen, ein großes Problem dar. Drittgenerations-EGFR-TKIs richten sich sowohl gegen aktivierende als auch gegen die Resistenz-vermittelnde T790M-Mutation. EGFR-TKIs der 3. Generation zeigen in klinischen Studien bei T790M-positiven Patienten relevante Wirksamkeit bei meist milden bis moderaten klassenspezifischen Nebenwirkungen. Molekularpathologischen Analysen kommt bei der Entscheidung zur Therapie mit Drittgenerations-EGFR-TKIs eine bedeutsame Rolle zu. In dieser Übersichtsarbeit wird der aktuelle Entwicklungsstand von Drittgenerations-EGFR-TKIs dargestellt mit einem Schwerpunkt auf Osimertinib, dem ersten und bislang einzigen in Deutschland zugelassenen Wirkstoff dieser Klasse. Zudem wird die Relevanz einer molekularen Diagnostik an Tumorgewebe bzw. an zirkulierender Tumor-DNA diskutiert.
- Published
- 2018
28. Patient-reported outcomes from STARTRK-2: a global phase II basket study of entrectinib for ROS1 fusion-positive non-small-cell lung cancer and NTRK fusion-positive solid tumours
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A.P. Conley, S. McCallum, D.M. Chen, Myung-Ju Ahn, Christian D. Rolfo, A. Kapre, Juergen Wolf, George D. Demetri, Takashi Seto, Salvatore Siena, S. Osborne, A. Drilon, Luis Paz-Ares, Fabrice Barlesi, Robert C. Doebele, and Hoffmann-La Roche
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Oncology ,Cancer Research ,medicine.medical_specialty ,Indazoles ,Lung Neoplasms ,Colorectal cancer ,entrectinib ,Population ,Entrectinib ,Proto-Oncogene Mas ,tyrosine kinase inhibitor ,Internal medicine ,Carcinoma, Non-Small-Cell Lung ,Proto-Oncogene Proteins ,Medicine ,Humans ,Patient Reported Outcome Measures ,Lung cancer ,education ,Adverse effect ,education.field_of_study ,business.industry ,Cancer ,Protein-Tyrosine Kinases ,medicine.disease ,Clinical trial ,patient-reported outcomes ,Cohort ,Benzamides ,Quality of Life ,business ,ROS1 ,NTRK - Abstract
Patient-reported outcomes (PROs) are increasingly relevant endpoints in clinical trials, contributing to our understanding of risk-benefit profiles, in addition to efficacy and safety data. We investigated the impact of entrectinib on patient-reported symptoms, functioning, and health-related quality of life. STARTRK-2 is a phase II basket study in patients with locally advanced/metastatic neurotrophic receptor tyrosine kinase 1/2/3 (NTRK1/2/3) and ROS proto-oncogene 1 (ROS1) fusion-positive solid tumours. PROs (prespecified secondary endpoint) were evaluated using the European Organization for Research and Treatment of Cancer quality-of-life questionnaire (QLQ-C30), lung cancer module (QLQ-LC13), and colorectal cancer module (QLQ-CR29), and the EuroQoL 5-Dimension 3-Level instruments, completed before cycle 1 day 1 and each subsequent 4-week cycle of entrectinib dosing, and the end of treatment. Adverse events and treatment-related symptoms were assessed in the safety analysis (SA)-PRO population. Tumour-related symptoms, functioning, and global health status were assessed in the efficacy analysis (EA)-PRO population. Data cut-offs: 31 October 2018 NTRK cohort; 01 May 2019 ROS1 cohort. SA-PRO populations comprised patients with NTRK fusion-positive solid tumours (N = 88) or ROS1 fusion-positive non-small-cell lung cancer (N = 180) who received one or more doses of entrectinib, completed PRO questionnaires on cycle 1 day 1 and answered one or more questions on-study. EA-PRO populations (N = 71) and (N = 145), respectively, comprised SA-PRO patients with measurable baseline disease. Moderate-to-high baseline global health status scores were maintained in EA-PRO populations during treatment. Role and physical functioning scores were moderate-to-high at baseline, with trends towards clinical improvement during treatment. Both cohorts reported low-to-moderate symptom burden at baseline, which was maintained or trended towards clinically meaningful improvement. Symptoms commonly associated with cancer treatment (e.g. nausea, fatigue) remained stable or improved during treatment. All SA-PRO patients experienced one or more adverse events, most frequently constipation or diarrhoea. PRO findings were consistent with the favourable safety profile of entrectinib, and further reinforce the positive benefit-risk profile of this treatment, indicating minimal overall treatment burden. This study was supported by F. Hoffmann-La Roche Ltd. Sí
- Published
- 2021
29. Systemnahe Programmierung mit C und Linux : Das umfassende Handbuch
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Jürgen Wolf, René Krooß, Jürgen Wolf, and René Krooß
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Alles zur systemnahen Anwendungsprogrammierung: von den E/A-Funktionen, dem Zugriff auf Systeminformationen über Prozesse, Signale, Interprozesskommunikation und Threads bis hin zu Netzwerkprogrammierung, Datenbanken und GUIs. Für alle, die Programme schreiben wollen und alte Software warten oder portieren müssen. Alle Beispiele sind auch auf dem Raspberry Pi ausführbar. Solide C- und Linux-Kenntnisse werden vorausgesetzt.Aus dem Inhalt:E/A-FunktionenAttribute von Dateien und VerzeichnissenZugriff auf SysteminformationenDevices – eine einfache Verbindung zur HardwareSystem- und BenutzerdateienDämonen, Zombies und ProzesseSignaleIPC – InterprozesskommunikationThreadsNetzwerkprogrammierungDatenbanken (MySQL, PostgreSQL)GUIs mit GTK+Werkzeuge für Programmierer
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- 2024
30. Fujifilm X-T50 : Das Handbuch zur Kamera
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Jürgen Wolf and Jürgen Wolf
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Die Fujifilm X-T50 ist leistungstechnisch der großen Schwester X-T5 sehr nahe, aber dennoch eigenständig: schick und griffig, leicht und kompakt, mit einem eigenen Bedienrad für die Filmsimulationen. Lassen Sie sich von der X-T50 begleiten und begleiten Sie Ihre Erlebnisse mit der X-T50! Mit diesem praxisbezogenen Handbuch bleibt Ihnen keine Funktion Ihrer Kamera verborgen.Aus dem Inhalt:Die Bedienelemente und Modi der X-T50Belichtung, Fokus und Weißabgleich steuern Mit den Fujifilm-Filmsimulationen fotografierenDie Kamera individuell konfigurierenGekonnt mit Blitz arbeitenDie X-T50 im Fotoalltag: Porträt, Landschaft, Makro, Action u. v. m.Filmen mit der X-T50Empfehlungen zu Objektiven und weiterem Zubehör
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- 2024
31. Menschen fotografieren : Das Praxisbuch für gute Porträts
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Maedeh Amini, Julius Erler, Jonas Hafner, Lisa Hafeneger, Felix Röser, Nora Scholz, Jürgen Wolf, Maedeh Amini, Julius Erler, Jonas Hafner, Lisa Hafeneger, Felix Röser, Nora Scholz, and Jürgen Wolf
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Fotografieren Sie Menschen in all ihren Facetten! In diesem Buch lernen Sie, wie ausdrucksstarke Porträtaufnahmen gelingen. Ob natürlich oder charakterstark, ob sinnlich oder fantasievoll – sieben Fotografinnen und Fotografen zeigen Ihnen, wie sie Menschen porträtieren. Sie lassen Sie teilhaben an ihren Bildideen und erklären, wie sie zu den gezeigten Ergebnissen gekommen sind. Tipps zum Umgang mit dem Modell, zur Lichtsetzung und zum Posing machen Ihr nächstes Porträtshooting zum Erfolg.Aus dem Inhalt:Natürliche und authentische Porträts fotografierenDen Charakter herausarbeitenMit fantasievollen Porträts Geschichten erzählenStrahlende Schönheit in Beauty- und Fashionporträts zeigenSinnlichkeit ästhetisch inszenierenKlassische und zeitlose Porträts aufnehmenVerbundenheit ausdrücken mit PaaraufnahmenSchwangere, Babys und Kinder optimal in Szene setzenMit zahlreichen Grundlagenexkursen zu Themen rund um das Shooting und die Fototechnik
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- 2024
32. Adobe Photoshop : Das umfassende Handbuch
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Sibylle Mühlke, Jürgen Wolf, Sibylle Mühlke, and Jürgen Wolf
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- Computer graphics, Photography--Digital techniques, Image processing--Digital techniques
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Das Standardwerk zu Adobe Photoshop! Sibylle Mühlke und Jürgen Wolf vermitteln geballtes Photoshop-Wissen und erklären alle Werkzeuge und Funktionen der Software – vom Öffnen einer Datei bis hin zur Arbeit mit 3D und Video. Sie erhalten zahlreiche Tipps und Hintergrundinfos, verstehen, welche Regler und Buttons Sie klicken müssen und haben Ihre Software von A bis Z im Griff! Alle wichtigen Themen werden anhand von Praxisbeispielen erklärt, die Sie Schritt für Schritt nachvollziehen können. Das benötigte Beispielmaterial steht Ihnen natürlich als Download zur Verfügung. So steht perfekten Retuschen, professionellen Montagen und selbst digitalen Gemälden nichts mehr im Wege.Komplett in Farbe, mit Tastenkürzel-Übersichten und Zusatzinfos zum Download – hier finden Sie als Einsteiger oder Fortgeschrittener immer genau das, was Sie brauchen! Aus dem Inhalt:Starthilfe für Neueinsteiger•innenBilder korrigieren und optimieren: Kontraste, Helligkeit und Schärfe, Farbkorrektur und Schwarzweiß, TonwertkorrekturRaw-Entwicklung mit Camera RawWeichzeichnung und SchärfentiefeHDR und PanoramenInhaltsbasierte Retusche, Bild- und Objektivfehler beheben, Perspektivkorrektur, FluchtpunktMalen mit Misch-Pinsel und Co.Texte und TextformatePhotoshop-Techniken: Masken, Auswahlen, Kanäle, Mischmodi, Ebenenstile, Filter, Smartobjekte, Pfade, FormwerkzeugeVideo- und 3D-BearbeitungAutomatisieren, FarbmanagementAusgabe für Druck und WebDie Fachpresse zur Vorauflage: Designer in Action: »Wer auf der Suche nach einem Buch ist, das möglichst alle wichtigen Funktionen von Photoshop abdeckt, Paletten bis ins Detail erklärt oder Filter ausführlich vorstellt, der ist hier richtig.« NaturFoto: »Auf mehr als 1.100 Seiten erklären Sibylle Mühlke und Jürgen Wolf alles, was man über das Arbeiten mit Photoshop wissen muss – mehr Photoshop geht wirklich nicht! Das Referenzwerk für jeden, der die Werkzeuge, Funktionen und Techniken von Grund auf erlernen möchte.«
- Published
- 2024
33. Canon EOS R100 : Das Handbuch zur Kamera
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Jürgen Wolf and Jürgen Wolf
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Den Sonnenaufgang in den Bergen, die ersten Schritte des Kindes oder einen Konzertbesuch mit Freuden – besondere Momente möchte man fotografisch festhalten. Wie das mit Ihrer Canon EOS R100 gelingt, erklärt Ihnen Jürgen Wolf in diesem Kamerahandbuch. Sie erfahren Schritt für Schritt und anhand vieler Beispiele aus der Praxis, wie Sie die Kamera in verschiedenen fotografischen Lebenslagen einsetzen. Lernen Sie alle Tasten und Einstellmöglichkeiten kennen, stellen Sie gezielt scharf und steuern Sie die Belichtung! So setzen Sie Ihre Motive gekonnt in Szene und nutzen die Möglichkeiten der Canon EOS R100 voll aus. Aus dem Inhalt:Die Canon EOS R100 sicher bedienenProgramme und Automatikfunktionen verstehenNicht zu hell, nicht zu dunkel – die Belichtung steuernFarben richtig einstellen mit dem WeißabgleichScharfe Fotos mit Autofokus oder manuellem FokussierenSerienbildfunktion und SelbstauslöserDie Canon EOS R100 in der Praxis: Porträts, Panoramen, Makroaufnahmen u. v. m.Blitzen mit der Canon EOS R100Filmen: Einstellungen und PraxistippsDie Canon EOS R100 individuell konfigurierenWelche Objektive und welches Zubehör sind sinnvoll?
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- 2024
34. Capture One Pro : Das umfassende Handbuch
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Jürgen Wolf and Jürgen Wolf
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Jürgen Wolf zeigt Ihnen in über 100 Workshops Schritt für Schritt, wie Sie Capture One Pro effizient einsetzen und Ihren Workflow aufbauen. Lernen Sie, mit Sessions oder Katalogen zu arbeiten. Archivieren und verwalten Sie Ihre Fotos. Bearbeiten Sie Ihre Raw-Bilder perfekt und veröffentlichen oder drucken Sie sie. Verstehen Sie Werkzeuge, Funktionen und Einstellungen im Detail, um besser entscheiden und zielgenauer arbeiten zu können. Nutzen Sie die neuen KI-Funktionen. Kurzum: Mit diesem Handbuch haben Sie Capture One Pro im Griff!Aus dem Inhalt:Grundlagen und ArbeitsbereichKataloge und SessionsCulling, Metadaten, Schlüsselwörter und FarbmarkierungenDer optimale EntwicklungsworkflowMotivgerechte EntwicklungHelligkeit und Kontrast optimierenSmart Adjustments für einheitliche Looks per KlickFarbkorrektur und SchwarzweißHDR und PanoramaExportieren, veröffentlichen und ausdruckenCapture One Pro individuell anpassenInkl. Capture One für iPad
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- 2024
35. LUMIX G9 II : Das Handbuch zur Kamera
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Jürgen Wolf and Jürgen Wolf
- Abstract
Robust, schnell und rundum gut ausgestattet: Die Panasonic LUMIX G9 II ist der leistungsfähige Allrounder im MFT-System. Sowohl für die Fotografie als auch für das Filmen. Mit diesem umfassenden Handbuch bleibt Ihnen keine Funktion Ihrer Kamera verborgen. Lernen Sie alle Funktionen und Einstellungen praxisorientiert kennen und setzen Sie Ihre Motive gekonnt in Szene.Aus dem Inhalt:Die Bedienelemente kennenlernenDie Programmmodi verwendenDie Belichtung steuernFokussieren mit der LUMIX G9 IIDie Farben steuernDie LUMIX G9 II individuell anpassenBlitzlicht einsetzenIn Feld und Flur mit der LUMIX G9 IIDie Filmfunktionen beherrschenZubehör für Ihre LUMIX G9 II
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- 2024
36. Mediengestaltung : Der Ausbildungsbegleiter
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Björn Rohles, Ralph Burkhardt, Jürgen Wolf, Daniel Schulte, Lars Kroll, Michael Rohrlich, Björn Rohles, Ralph Burkhardt, Jürgen Wolf, Daniel Schulte, Lars Kroll, and Michael Rohrlich
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Du bist Mediengestalter bzw. Mediengestalterin in der Ausbildung und suchst Hilfe bei der Vorbereitung auf die Zwischen- oder Abschlussprüfung? Dieses Handbuch ist übersichtlich gestaltet, gut zu lesen, auf dem aktuellen Stand und bringt die Themen auf den Punkt, die du beherrschen musst: Angefangen bei Kommunikationstechnologien über Typografie, Layout und Reinzeichnung bis hin zu Druckvorstufe und Druck und Webdesign, EDV-Wissen und Informationstechnik. Das geballte Mediengestalterwissen – so gehst du top vorbereitet in die Prüfung.Aus dem Inhalt:Das Berufsbild Mediengestalter•inEDV-GrundlagenGestaltungsgrundlagen, Layout, Typografie, Farbe, BilderGestaltungsprojekte (Plakat, Flyer, Broschüre, Buchgestaltung), Corporate Design, Logodesign, InfografikDigitale Druckvorstufe, Bildbearbeitung, Druck, Papier, WeiterverarbeitungApp-Design, E-Books, Video, Digitale FotografieSocial Media, Marketing für die MediengestaltungGrundlagen der Programmierung, Objektorientierte ProgrammierungInternet, Webprogrammierung, Programmiersprachen, Server-Technologien, DatenbankenResponsive Webdesign, User Experience, WebgestaltungInformationstechnik, Netzwerke, SicherheitMedienrecht
- Published
- 2024
37. Fujifilm X100VI : Das Handbuch zur Kamera
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Jürgen Wolf and Jürgen Wolf
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Markantes Äußeres mit Wiedererkennungseffekt: Die Fujifilm X100VI ist die sechste Generation der Premiumkompaktkamera mit nun einem 40-Megapixel-APS-C-Sensor und der bewährten festen Reportage-Brennweite. Die Kamera wurde in zahlreichen Details verbessert und ist – wie ihre Vorgänger – wieder die perfekte Kamera für Street und Reise. Jürgen Wolf zeigt Ihnen, wie Sie das Beste aus der Fujifilm X100VI herausholen!Aus dem Inhalt:Bedienelemente und BedienkonzeptDie Fujifilm X100VI personalisierenDie Belichtung steuernPräzise fokussierenFilmsimulationen und BildeffektePraxistipps für den FotoalltagKonverter und weiteres ZubehörFilmen mit der Fujifilm X100VI
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- 2024
38. 1256P Capmatinib safety update in MET dysregulated NSCLC from the GEOMETRY mono-1 trial
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O. Tanriverdi, Juergen Wolf, A. Chassot Agostinho, Anna Robeva, Edward B. Garon, M. Carbini, Daniel Shao Weng Tan, Rebecca S. Heist, Hendricus Groen, and S. Le Mouhaer
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Oncology ,medicine.medical_specialty ,Capmatinib ,business.industry ,Internal medicine ,medicine ,Hematology ,business - Published
- 2021
39. 436P Phase (Ph) II study of taminadenant (NIR178) + spartalizumab (PDR001) in patients (pts) with microsatellite stable (MSS) colorectal cancer (CRC)
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M.S. Carlino, P. Grell, Somesh Choudhury, M.J.A. de Jonge, D.S.W. Tan, G. Jerusalem, Silvia Damian, V. Nesbitt, Stefan Kasper, Ticiana A. Leal, X. Yang, J. Otero, L. Ho Lee, Juergen Wolf, O. Saavedra Santa Gadea, Richard Greil, Timothy A. Yap, Zev A. Wainberg, J W Kim, and Markus Joerger
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Oncology ,medicine.medical_specialty ,Colorectal cancer ,business.industry ,Microsatellite Stable ,Phase (matter) ,Internal medicine ,medicine ,In patient ,Hematology ,medicine.disease ,business - Published
- 2021
40. First constraints on the AGN X-ray luminosity function at $z \sim 6$ from an eROSITA-detected quasar
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H. J. A. Röttgering, Andrea Merloni, Timothy W. Shimwell, Juergen Wolf, Aidan Hotan, Johan Comparat, Matthew Whiting, Vanessa A. Moss, A. Georgakakis, Kirpal Nandra, Mara Salvato, Arne Rau, R. Arcodia, Tanya Urrutia, Georg Lamer, D. N. Hoang, Tie Liu, F. de Gasperin, W. L. Williams, Johannes Buchner, Marcus Brüggen, Marcella Brusa, Wolf J., Nandra K., Salvato M., Liu T., Buchner J., Brusa M., Hoang D.N., Moss V., Arcodia R., Bruggen M., Comparat J., De Gasperin F., Georgakakis A., Hotan A., Lamer G., Merloni A., Rau A., Rottgering H.J.A., Shimwell T.W., Urrutia T., Whiting M., and Williams W.L.
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Astrophysics - astrophysics of galaxies ,Astrophysics::High Energy Astrophysical Phenomena ,Population ,FOS: Physical sciences ,Context (language use) ,Astrophysics ,Astrophysics::Cosmology and Extragalactic Astrophysics ,01 natural sciences ,Astrophysics - high energy astrophysical phenomena ,0103 physical sciences ,Quasars: individual: SDSS J083643.85+005453.3 ,education ,010303 astronomy & astrophysics ,Luminosity function ,Astrophysics::Galaxy Astrophysics ,Physics ,High Energy Astrophysical Phenomena (astro-ph.HE) ,education.field_of_study ,COSMIC cancer database ,Accretion (meteorology) ,010308 nuclear & particles physics ,Galaxies: high-redshift ,Astronomy and Astrophysics ,Quasar ,LOFAR ,Redshift ,X-rays: galaxies ,Space and Planetary Science ,Astrophysics of Galaxies (astro-ph.GA) - Abstract
Context. High-redshift quasars signpost the early accretion history of the Universe. The penetrating nature of X-rays enables a less absorption-biased census of the population of these luminous and persistent sources compared to optical/near-infrared colour selection. The ongoing SRG/eROSITA X-ray all-sky survey offers a unique opportunity to uncover the bright end of the high-z quasar population and probe new regions of colour parameter space. Aims. We searched for high-z quasars within the X-ray source population detected in the contiguous ~140 deg2 field observed by eROSITA during the performance verification phase. With the purpose of demonstrating the unique survey science capabilities of eROSITA, this field was observed at the depth of the final all-sky survey. The blind X-ray selection of high-redshift sources in a large contiguous, near-uniform survey with a well-understood selection function can be directly translated into constraints on the X-ray luminosity function (XLF), which encodes the luminosity-dependent evolution of accretion through cosmic time. Methods. We collected the available spectroscopic information in the eFEDS field, including the sample of all currently known optically selected z > 5.5 quasars and cross-matched secure Legacy DR8 counterparts of eROSITA-detected X-ray point-like sources with this spectroscopic sample. Results. We report the X-ray detection of eFEDSU J083644.0+005459, an eROSITA source securely matched to the well-known quasar SDSS J083643.85+005453.3 (z = 5.81). The soft X-ray flux of the source derived from eROSITA is consistent with previous Chandra observations. The detection of SDSS J083643.85+005453.3 allows us to place the first constraints on the XLF at z > 5.5 based on a secure spectroscopic redshift. Compared to extrapolations from lower-redshift observations, this favours a relatively flat slope for the XLF at z ~ 6 beyond L*, the knee in the luminosity function. In addition, we report the detection of the quasar with LOFAR at 145 MHz and ASKAP at 888 MHz. The reported flux densities confirm a spectral flattening at lower frequencies in the emission of the radio core, indicating that SDSS J083643.85+005453.3 could be a (sub-) gigahertz peaked spectrum source. The inferred spectral shape and the parsec-scale radio morphology of SDSS J083643.85+005453.3 indicate that it is in an early stage of its evolution into a large-scale radio source or confined in a dense environment. We find no indications for a strong jet contribution to the X-ray emission of the quasar, which is therefore likely to be linked to accretion processes. Conclusions. Our results indicate that the population of X-ray luminous AGNs at high redshift may be larger than previously thought. From our XLF constraints, we make the conservative prediction that eROSITA will detect ~90 X-ray luminous AGNs at redshifts 5.7 < z < 6.4 in the full-sky survey (De+RU). While subject to different jet physics, both high-redshift quasars detected by eROSITA so far are radio-loud; a hint at the great potential of combined X-ray and radio surveys for the search of luminous high-redshift quasars.
- Published
- 2021
- Full Text
- View/download PDF
41. Durvalumab as third-line or later treatment for advanced non-small-cell lung cancer (ATLANTIC): an open-label, single-arm, phase 2 study
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Marina Chiara Garassino, Byoung-Chul Cho, Joo-Hang Kim, Julien Mazières, Johan Vansteenkiste, Hervé Lena, Jesus Corral Jaime, Jhanelle E Gray, John Powderly, Christos Chouaid, Paolo Bidoli, Paul Wheatley-Price, Keunchil Park, Ross A Soo, Yifan Huang, Catherine Wadsworth, Phillip A Dennis, Naiyer A Rizvi, Luis Paz-Ares Rodriguez, Silvia Novello, Sandrine Hiret, Peter Schmid, Eckart Laack, Raffaele Califano, Makoto Maemondo, Sang-We Kim, Jamie Chaft, David Vicente Baz, Thierry Berghmans, Dong-Wan Kim, Veerle Surmont, Martin Reck, Ji-Youn Han, Esther Holgado Martin, Cristobal Belda Iniesta, Yuichiro Oe, Antonio Chella, Akhil Chopra, Gilles Robinet, Hector Soto Parra, Michael Thomas, Parneet Cheema, Nobuyuki Katakami, Wu-Chou Su, Young-Chul Kim, Juergen Wolf, Jong-Seok Lee, Hideo Saka, Michele Milella, Inmaculada Ramos Garcia, Anne Sibille, Takashi Yokoi, Eun Joo Kang, Shinji Atagi, Ernst Spaeth-Schwalbe, Makoto Nishio, Fumio Imamura, Nashat Gabrail, Remi Veillon, Sofie Derijcke, Tadashi Maeda, Dylan Zylla, Kendra Kubiak, Armando Santoro, Ma. Noemi Uy, Sarayut Lucien Geater, Antoine Italiano, Dariusz Kowalski, Fabrice Barlesi, Yuh-Min Chen, David Spigel, Busyamas Chewaskulyong, Ramon Garcia Gomez, Rosa Alvarez Alvarez, Chih-Hsin Yang, Te-Chun Hsia, Fabrice Denis, Hiroshi Sakai, Mark Vincent, Koichi Goto, Joaquim Bosch-Barrera, Glen Weiss, Jean-Luc Canon, Christian Scholz, Massimo Aglietta, Hirotsugu Kemmotsu, Koichi Azuma, Penelope Bradbury, Ronald Feld, Abraham Chachoua, Jacek Jassem, Rosalyn Juergens, Ramon Palmero Sanchez, Albert Malcolm, Nandagopal Vrindavanam, Kaoru Kubota, Cornelius Waller, David Waterhouse, Bruno Coudert, Zsuzsanna Mark, Miyako Satouchi, Gee-Chen Chang, Christian Herzmann, Arvind Chaudhry, Selvaraj Giridharan, Paul Hesketh, Norihiko Ikeda, Ralph Boccia, Nichola Iannotti, Missak Haigentz, John Reynolds, John Querol, Kazuhiko Nakagawa, Shunichi Sugawara, Eng Huat Tan, Tomonori Hirashima, Scott Gettinger, Terufumi Kato, Koji Takeda, Oscar Juan Vidal, Andrea Mohn-Staudner, Amit Panwalkar, Davey Daniel, Kunihiko Kobayashi, Guia Elena Imelda Ladrera, Clemens Schulte, Martin Sebastian, Marketa Cernovska, Helena Coupkova, Libor Havel, Norbert Pauk, Joginder Singh, Shuji Murakami, Tibor Csoszi, Gyorgy Losonczy, Allan Price, Ian Anderson, Mussawar Iqbal, Vamsee Torri, Erzsebet Juhasz, Saleem Khanani, Leona Koubkova, Benjamin Levy, Ray Page, Csaba Bocskei, Lucio Crinò, David Einspahr, Christopher Hagenstad, Necy Juat, Lindsay Overton, Mitchell Garrison, Zsuzsanna Szalai, IRCCS Istituto Nazionale dei Tumori [Milano], Yonsei University College of Medicine, CHA Bundang Medical Center, Service Pneumologie-Allergologie [CHU Toulouse], Pôle Clinique des Voies respiratoires [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), University Hospitals KU Leuven, Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hospital Universitario Virgen del Rocío [Sevilla], H. Lee Moffitt Cancer Center and Research Institute, Carolina BioOncology Institute, Service de Pneumologie [CHI Créteil], CHI Créteil, IMRB - CEPIA/'Clinical Epidemiology And Ageing : Geriatrics, Primary Care and Public Health' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Azienda Ospedaliera San Gerardo, The Ottawa Hospital Research Institute, Centre for Rehabilitation Research and Development, 505 Smyth Road, Ottawa, ON, Canada, K1H 8M2., Samsung Medical Center Sungkyunkwan University School of Medicine, Institute Division of Hematology/Oncology, National University Hospital and National University Cancer Institute, AstraZeneca, Gaithersburg, MD, USA, AstraZeneca [Cambridge, UK], Columbia University [New York], Università degli studi di Torino = University of Turin (UNITO), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Department of Mathematics [Imperial College London], Imperial College London, Université libre de Bruxelles (ULB), Department of Microbiology, Chang Won National University, German Center for Lung Research, Università degli studi di Palermo - University of Palermo, Garassino, M, Cho, B, Kim, J, Mazieres, J, Vansteenkiste, J, Lena, H, Jaime, J, Gray, J, Powderly, J, Chouaid, C, Bidoli, P, Wheatley-Price, P, Park, K, Soo, R, Huang, Y, Wadsworth, C, Dennis, P, and Rizvi, N
- Subjects
0301 basic medicine ,Oncology ,Male ,Durvalumab ,Lung Neoplasms ,Phases of clinical research ,B7-H1 Antigen ,0302 clinical medicine ,Antineoplastic Agents, Immunological ,4-Butyrolactone ,Carcinoma, Non-Small-Cell Lung ,Anaplastic lymphoma kinase ,Anaplastic Lymphoma Kinase ,Fatigue ,Antibodies, Monoclonal ,phase 2 study ,gamma-Glutamyltransferase ,Middle Aged ,Progression-Free Survival ,ErbB Receptors ,ATLANTIS ,Response Evaluation Criteria in Solid Tumors ,Oncology, Durvalumab, non-small-cell lung cancer , ATLANTIS, phase 2 study ,030220 oncology & carcinogenesis ,Cohort ,Female ,Immunotherapy ,Diarrhea ,medicine.medical_specialty ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Article ,03 medical and health sciences ,Internal medicine ,medicine ,Humans ,Progression-free survival ,Aspartate Aminotransferases ,Lung cancer ,Aged ,Performance status ,business.industry ,Pneumonia ,medicine.disease ,Injection Site Reaction ,030104 developmental biology ,non-small-cell lung cancer ,Mutation ,business - Abstract
Background: Immune checkpoint inhibitors are a new standard of care for patients with advanced non-small-cell lung cancer (NSCLC) without EGFR tyrosine kinase or anaplastic lymphoma kinase (ALK) genetic aberrations (EGFR−/ALK−), but clinical benefit in patients with EGFR mutations or ALK rearrangements (EGFR+/ALK+) has not been shown. We assessed the effect of durvalumab (anti-PD-L1) treatment in three cohorts of patients with NSCLC defined by EGFR/ALK status and tumour expression of PD-L1. Methods: ATLANTIC is a phase 2, open-label, single-arm trial at 139 study centres in Asia, Europe, and North America. Eligible patients had advanced NSCLC with disease progression following at least two previous systemic regimens, including platinum-based chemotherapy (and tyrosine kinase inhibitor therapy if indicated); were aged 18 years or older; had a WHO performance status score of 0 or 1; and measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Key exclusion criteria included mixed small-cell lung cancer and NSCLC histology; previous exposure to any anti-PD-1 or anti-PD-L1 antibody; and any previous grade 3 or worse immune-related adverse event while receiving any immunotherapy agent. Patients in cohort 1 had EGFR+/ALK+ NSCLC with at least 25%, or less than 25%, of tumour cells with PD-L1 expression. Patients in cohorts 2 and 3 had EGFR−/ALK− NSCLC; cohort 2 included patients with at least 25%, or less than 25%, of tumour cells with PD-L1 expression, and cohort 3 included patients with at least 90% of tumour cells with PD-L1 expression. Patients received durvalumab (10 mg/kg) every 2 weeks, via intravenous infusion, for up to 12 months. Retreatment was allowed for patients who benefited but then progressed after completing 12 months. The primary endpoint was the proportion of patients with increased tumour expression of PD-L1 (defined as ≥25% of tumour cells in cohorts 1 and 2, and ≥90% of tumour cells in cohort 3) who achieved an objective response, assessed in patients who were evaluable for response per independent central review according to RECIST version 1.1. Safety was assessed in all patients who received at least one dose of durvalumab and for whom any post-dose data were available. The trial is ongoing, but is no longer open to accrual, and is registered with ClinicalTrials.gov, number NCT02087423. Findings: Between Feb 25, 2014, and Dec 28, 2015, 444 patients were enrolled and received durvalumab: 111 in cohort 1, 265 in cohort 2, and 68 in cohort 3. Among patients with at least 25% of tumour cells expressing PD-L1 who were evaluable for objective response per independent central review, an objective response was achieved in 9 (12·2%, 95% CI 5·7–21·8) of 74 patients in cohort 1 and 24 (16·4%, 10·8–23·5) of 146 patients in cohort 2. In cohort 3, 21 (30·9%, 20·2–43·3) of 68 patients achieved an objective response. Grade 3 or 4 treatment-related adverse events occurred in 40 (9%) of 444 patients overall: six (5%) of 111 patients in cohort 1, 22 (8%) of 265 in cohort 2, and 12 (18%) of 68 in cohort 3. The most common treatment-related grade 3 or 4 adverse events were pneumonitis (four patients [1%]), elevated gamma-glutamyltransferase (four [1%]), diarrhoea (three [1%]), infusion-related reaction (three [1%]), elevated aspartate aminotransferase (two [
- Published
- 2020
42. Grundkurs Gutes Webdesign : Alles, was Sie über Gestaltung im Web wissen sollten
- Author
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Björn Rohles, Jürgen Wolf, Björn Rohles, and Jürgen Wolf
- Subjects
- Web sites--Design
- Abstract
Eine gute Website? Klar, die ist vor allem informativ, schnell und funktional. Aber was macht aus einer einfachen Website einen echten Hingucker? Einen, der im Gedächtnis bleibt, weil er einfach richtig gut gestaltet wurde? In diesem Buch erfahren Sie es, denn hier erlernen Sie alle Gestaltungsgrundlagen für gutes Webdesign – vom perfekten Layout über die richtigen Farben und die passende Schrift bis hin zum Design von Grafiken, Bildern und Icons. Das Besondere dabei: Der Autor zeigt Ihnen in einem Beispielprojekt und in vielen zusätzlichen Praxisbeispielen, wie Sie diese Gestaltungsprinzipien im Web anwenden und sie konkret umsetzen. Dass dabei mit HTML5 und CSS3 gearbeitet wird, versteht sich von selbst. Auch Barrierefreiheit, Usability und Responsive Webdesign werden groß geschrieben. So entstehen moderne und attraktive Websites, die jeder gerne besucht!Aus dem Inhalt:Website-KonzeptionResponsive WebdesignIdeen finden und bewertenTypografie, WebfontsFarblehre, Farbe im WebGrafiken, Bilder, Icons, Buttons, Links, NavigationInformationsarchitekturCSS-Layouts, RasterHTML5 und CSS3Usability, BarrierefreiheitNachhaltiges WebdesignTesten und optimieren, SuchmaschinenoptimierungDie Fachpresse zur Vorauflage: maclife.de: »Ein toll gestaltetes und umfassendes Werk für alle Anwender, die anspruchsvolle Webseiten entwerfen, gestalten und betreiben möchten.«
- Published
- 2023
43. C von A bis Z : Das umfassende Handbuch
- Author
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Jürgen Wolf, René Krooß, Jürgen Wolf, and René Krooß
- Subjects
- C (Computer program language)--Handbooks, manuals, etc
- Abstract
Unser beliebter Klassiker in fünfter Auflage. Zum aktuellen Standard C23 und mit einem Autorenteam aus Praxis und Lehre. Lassen Sie sich umfassend einführen oder nutzen Sie das Buch als Nachschlagewerk. Von den Grundlagen über die dynamische Speicherverwaltung bis zur plattformübergreifenden Entwicklung. Randvoll mit hilfreichen Beispielen und Praxistipps – C-Wissen pur!Aus dem Inhalt:DatenstrukturenAlgorithmenSicherheitDynamische SpeicherverwaltungNetzwerkprogrammierungCross-Plattform-EntwicklungParallele ProgrammierungAuf Datenbanken zugreifenCodebeispiele und Praxistipps
- Published
- 2023
44. HTML und CSS : Das umfassende Handbuch
- Author
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Jürgen Wolf and Jürgen Wolf
- Subjects
- Cascading style sheets, JavaScript (Computer program language), Ajax (Web site development technology), Web site development, Internet programming, HTML (Document markup language)
- Abstract
Moderne Web-Technologien für moderne Websites! In diesem Standardwerk gibt Ihnen Jürgen Wolf alle Werkzeuge an die Hand, die sie für einen starken Auftritt im Web benötigen. Lernen Sie alle Grundlagen von HTML, CSS und JavaScript kennen und erweitern Sie Ihr Wissen mit diesem umfassenden Lern- und Nachschlagewerk: vom Aufbau eines HTML-Dokuments über die Gestaltung mit CSS bis hin zur Web-Programmierung mit JavaScript. Inkl. einer Einführung in die wichtigen JavaScript-Frameworks React und Angular.Aus dem Inhalt:Syntax und Aufbau von HTML-DokumentenTabellen und HyperlinksBilder, Videos und AudioHTML-Formulare und interaktive ElementeDie Selektoren von CSSVererbung und KaskadeFlexboxen und Grid LayoutsResponsive Layouts erstellenEinführung in die JavaScript-APIsEinführung in React und Angular
- Published
- 2023
45. HTML and CSS : The Comprehensive Guide
- Author
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Jürgen Wolf and Jürgen Wolf
- Subjects
- Web site development, Cascading style sheets, HTML (Document markup language)
- Abstract
Web developers—this is your all-in-one guide to HTML and CSS! Learn to use HTML to format text and structure web pages. Understand the HTML document skeleton before creating forms, referencing hyperlinks, embedding active content, and more. Then style your pages with CSS: Create consistent designs with selectors, the box model, the cascade algorithm, and inheritance. Round out your client-side development experience by getting to know JavaScript. With detailed code examples, you'll master HTML and CSS in no time! a. HTML for Formatting and Structure Master HTML syntax and document structure. Work with tags, elements, and attributes to build HTML documents. Create tables and forms, embed images, configure links, and develop interactive HTML elements. b. CSS for Style and Design Develop simple and complex web layouts with CSS rules, selectors, declarations, combinators, pseudoclasses, and pseudoelements. Understand the principles of cascading, specificity, and inheritance. Learn to use the CSS box model, the position property, and more. c. JavaScript Fundamentals Expand your knowledge with an introduction to JavaScript. See how to use variables, statements, functions, arrays, and objects to write and run simple programs. Explore the basics of Ajax for interactive web application design. Highlights: HTML syntax and structure HTML elements Tables, links, and images HTML forms CSS selectors Cascade and inheritance CSS box model CSS preprocessors Responsive layout design Testing JavaScript Ajax
- Published
- 2023
46. Photoshop Elements 2024 : Das umfassende Handbuch
- Author
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Jürgen Wolf and Jürgen Wolf
- Subjects
- Photography--Digital techniques, Image processing--Digital techniques, Digital images--Editing
- Abstract
Holen Sie das Beste aus Ihren Bildern heraus – mit Photoshop Elements 2024 und diesem umfassenden Handbuch! Der begeisterte Digitalfotograf Jürgen Wolf erklärt Ihnen verständlich und praxisbezogen, wie Sie Ihre Fotos optimieren, Bildfehler korrigieren oder kreative Montagen und Collagen erstellen. Schaffen Sie mit dem Organizer Ordnung in Ihrer Bildersammlung. Nutzen Sie spezielle Filter für einen ganz besonderen Foto-Look. Ihr Lieblingsbild hat einen Farbstich? Kein Problem! Egal, was Sie mit Photoshop Elements machen wollen – in diesem Buch erfahren Sie, wie es geht!Selbst knifflige Aufgaben werden Sie erfolgreich bewältigen. Zahlreiche Workshops und Profi-Tipps helfen Ihnen dabei. Damit Sie alle Schritte anschaulich nachvollziehen können, stehen Ihnen Beispielbilder als Download zur Verfügung. So tauchen Sie Schritt für Schritt tiefer in die Bildbearbeitung mit Photoshop Elements 2024 ein.Aus dem Inhalt:Die neue Programmoberfläche kennenlernenBilder übersichtlich verwaltenUmfangreiche Bildkorrekturen meisternMit Farben die Bildwirkung beeinflussenAuswahlen erstellen und Objekte freistellenMit Ebenen gezielt und kreativ arbeitenPorträts perfekt retuschierenTexte und Formen einsetzenCollagen, Montagen und Panoramen mit Photomerge erstellenBilder wirkungsvoll präsentierenFarbprofile, Plug-ins und Tastenkürzel nutzenMit vielen Beispielbildern zum Download
- Published
- 2023
47. Fujifilm X-S20 : Das Handbuch zur Kamera
- Author
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Jürgen Wolf and Jürgen Wolf
- Abstract
Top Leistung in einem handlichen Paket! Die Fujifilm X-S20 hat viele Fähigkeiten der Topmodelle und trägt dabei nicht dick auf: CMOS-4-Sensor, X-Prozessor 5, Vlog-Modus, 5-Achsen-IBIS, 6,2K, AF mit Motiverkennung u. v. m. Mit diesem umfassenden und praxisorientierten Handbuch lernen Sie alle Einstellungen Ihrer Kamera im Detail kennen, um Ihre Motive gekonnt in Szene zu setzen und die Möglichkeiten der X-S20 voll auszunutzen. Zu Hause und auf Reisen, mit Fotos und in bewegten Bildern!Aus dem Inhalt:Bedienelemente und BedienkonzeptDie Programmmodi verwendenDie Belichtung steuernFokussieren mit der X-S20Die Farben steuernDie X-S20 individuell anpassenBlitzen mit der X-S20Der Alltag mit der X-S20Filmen und VloggenInteressantes Zubehör
- Published
- 2023
48. Fujifilm X-T5 : Das Handbuch zur Kamera
- Author
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Jürgen Wolf and Jürgen Wolf
- Abstract
Die Fujifilm X-T5 ist eine leistungsstarke Kamera für enthusiastische Fotograf•innen. Und wenn Ihnen nach Bewegtbild ist, dann filmen Sie in 6,2K-Auflösung. Die X-T5 ist mehr denn je eine zuverlässige Begleiterin für kreative Projekte jeglicher Couleur. Mit diesem umfassenden Handbuch bleibt Ihnen keine Funktion Ihrer Kamera verborgen. Lernen Sie alle Funktionen und Einstellungen praxisorientiert kennen und setzen Sie Ihre Motive gekonnt in Szene.Aus dem Inhalt:Bedienelemente und Bedienkonzept der KameraDie Programmmodi verwendenDie Belichtung steuernFokussieren mit der X-T5Die Farben steuernDie X-T5 individuell anpassenBlitzen mit der X-T5Der Alltag mit der X-T5Filmen mit der X-T5Fotos und Filme bearbeitenZubehör für Ihre X-T5Die Menüs im Überblick
- Published
- 2023
49. Capture One Pro 23 : Das umfassende Handbuch
- Author
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Jürgen Wolf and Jürgen Wolf
- Abstract
Hier finden Sie alles zu Capture One Pro 23! Jürgen Wolf zeigt Ihnen schrittweise in zahlreichen Workshops, wie Sie die Software effizient einsetzen und Ihren Workflow aufbauen. Lernen Sie, mit Sessions oder Katalogen zu arbeiten. Archivieren und verwalten Sie Ihre Bilder. Bearbeiten Sie Ihre Raw-Bilder perfekt und veröffentlichen oder drucken Sie sie. Verstehen Sie Werkzeuge, Funktionen und Einstellungen im Detail, um besser entscheiden und zielgenauer arbeiten zu können! Mit diesem Handbuch haben Sie Capture One Pro 23 im Griff!Aus dem Inhalt:Die ersten SchritteGrundlagen und ArbeitsbereichKataloge und SessionsCulling – effiziente BildauswahlMetadaten, Schlüsselwörter und FarbmarkierungenDer optimale EntwicklungsworkflowMotivgerechte EntwicklungSmart Adjustments für einheitliche Looks per KlickHelligkeit und Kontrast optimierenFarbkorrektur und SchwarzweißGesichts- und Beauty-RetuscheHDR und PanoramaExportieren, veröffentlichen und ausdruckenCapture One Pro individuell anpassenInkl. Capture One für iPad
- Published
- 2023
50. Prevalence and potential biological role of TERT amplifications in ALK translocated adenocarcinoma of the lung
- Author
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Till Baar, Reinhard Buettner, Carina Heydt, Christina Alidousty, Barbara Holz, Luciano G. Martelotto, Anne M. Schultheis, Nicolai Duerbaum, Janna Siemanowski, Svenja Wagener-Ryczek, Elke Binot, Jana Fassunke, Juergen Wolf, Anna Kron, and Sabine Merkelbach-Bruse
- Subjects
0301 basic medicine ,Histology ,Lung Neoplasms ,Context (language use) ,Adenocarcinoma of Lung ,Biology ,Genome ,Translocation, Genetic ,Pathology and Forensic Medicine ,03 medical and health sciences ,0302 clinical medicine ,hemic and lymphatic diseases ,Chromosome instability ,Carcinoma, Non-Small-Cell Lung ,medicine ,Adenocarcinoma of the lung ,Humans ,Anaplastic Lymphoma Kinase ,Treatment resistance ,Lung cancer ,Gene ,Lung ,Telomerase ,In Situ Hybridization, Fluorescence ,Cancer ,General Medicine ,medicine.disease ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cancer research - Abstract
Aims The advent of specific ALK-targeting drugs has radically changed the outcome of patients with ALK translocated non-small-cell lung cancer (NSCLC). However, emerging resistance to treatment with ALK inhibitors in these patients remains a major concern. In previous studies, we analysed two ALK+ patient cohorts (TP53 wild-type/TP53 mutated) in terms of copy number alterations. All patients belonging to the TP53 wild-type group had mainly genetically stable genomes, with one exception showing chromosomal instability and amplifications of several gene loci, including TERT. Here, we aimed to determine the prevalence of TERT amplifications in these ALK+ lung cancer patients by analysing an independent cohort of 109 ALK translocated cases. We further analysed the copy numbers of numerous cancer-relevant genes and other genetic aberrations. Methods and results The prevalence of TERT amplifications was determined by means of FISH analyses. Copy numbers of 87 cancer-relevant genes were determined by NanoString nCounter® technology, FoundationOne® and lung-specific NGS panels in some of these TERT-amplified samples, and clinical data on patients with TERT-amplified tumours were collected. Our data revealed that five (4.6%) of all 109 analysed ALK+ patients harboured amplification of TERT and that these patients had genetically unstable genomes. Conclusions Our preliminary study shows that ALK+ adenocarcinomas should be evaluated in the context of their genomic background in order to more clearly understand and predict patients' individual course of disease.
- Published
- 2020
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