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1. Overall survival and central nervous system activity of crizotinib in ROS1-rearranged lung cancer—final results of the EUCROSS trial

Author

Michels, S., Massutí, B., Vasyliv, I., Stratmann, J., Frank, J., Adams, A., Felip, E., Grohé, C., Rodriguez-Abreu, D., Bischoff, H., Carcereny i Costa, E., Corral, J., Pereira, E., Fassunke, J., Fischer, R.N., Insa, A., Koleczko, S., Nogova, L., Reck, M., Reutter, T., Riedel, R., Schaufler, D., Scheffler, M., Weisthoff, M., Provencio, M., Merkelbach-Bruse, S., Hellmich, M., Sebastian, M., Büttner, R., Persigehl, T., Rosell, R., and Wolf, J.

Published
2024
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2. Impact of TP53 mutation status on systemic treatment outcome in ALK-rearranged non-small-cell lung cancer

Author

Kron, A., Alidousty, C., Scheffler, M., Merkelbach-Bruse, S., Seidel, D., Riedel, R., Ihle, M.A., Michels, S., Nogova, L., Fassunke, J., Heydt, C., Kron, F., Ueckeroth, F., Serke, M., Krüger, S., Grohe, C., Koschel, D., Benedikter, J., Kaminsky, B., Schaaf, B., Braess, J., Sebastian, M., Kambartel, K -O, Thomas, R., Zander, T., Schultheis, A.M., Büttner, R., and Wolf, J.

Published
2018
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8. 1431P The nNGM Preclinical Platform: Preclinical research to generate evidence for patients with non-small cell lung cancer harboring variants of unknown significance

Author

Ziegler, M., Albers-Leischner, C., Salgueiro, L., Khoury, N., Sharapova, Y., Saalfeld, F.C., Wenzel, C., Scharpenseel, H., Schmidt, C., Naveja-Romero, J., Meemboor, S., Hillmer, A., Nogova, L., Wermke, M., Wolf, J., Diederichs, S., Brummer, T., Büttner, R., Janning, M., and Loges, S.

Published
2023
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20. 1028P BIOLUMA: A phase II trial of nivolumab in combination with ipilimumab to evaluate efficacy and safety in lung cancer and to evaluate biomarkers predictive for response – results from the NSCLC cohort

Author

Fischer, R.N., George, J., Scheel, A., Schloesser, H., Brossart, P., Engel-Riedel, W., Griesinger, F., Grohé, C., Kern, J.K., Panse, J., Sebastian, M., Serke, M., Wiewrodt, R., Michels, S., Nogova, L., Riedel, R., Weber, J-P., Büttner, R., Thomas, R., and Wolf, J.

Published
2022
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25. OA15.05 BIOLUMA: A Phase II Trial of Nivolumab and Ipilimumab in Lung Cancer – Prospective Evaluation of TMB in SCLC Patients

Author

Fischer, R., George, J., Scheel, A., Schlösser, H., Vehreschild, M., Abdulla, D., Koleczko, S., Michels, S., Nogova, L., Riedel, R., Scheffler, M., Maas, L., Brossart, P., Engel-Riedel, W., Griesinger, F., Grohé, C., Kern, J., Hermes, B., Nachtkamp, K., Panse, J., Sebastian, M., Lehmann, M., Wiewrodt, R., Buettner, R., Thomas, R., and Wolf, J.

Published
2019
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27. 1548P - Crizotinib in patients with advanced or metastatic ROS1-rearranged lung cancer (EUCROSS): A European phase II clinical trial – Updated progression-free survival, overall survival and mechanisms of resistance

Author

Michels, S., Massuti Sureda, B., Schildhaus, H.-U., Franklin, J., Sebastian, M., Felip, E., Grohe, C., Rodríguez-Abreu, D.F., Bischoff, H., Carcereny Costa, E., Corral Jaime, J., Insa, A., Reck, M., Scheffler, M., Karachaliou, N., Merkelbach-Bruse, S., Nogova, L., Büttner, R., Rosell, R., and Wolf, J.

Published
2019
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35. 1213PD - A comprehensive analysis of potentially targetable genetic aberrations and clinical findings in 821 patients with squamous-cell NSCLC – a comparison of NGM and TCGA LUSC data

Author

Koleczko, S., Schäpers, C., Scheffler, M., Ihle, M., Kostenko, A., Michels, S., Fischer, R., Nogova, L., Brandes, V., Abdulla, D., Ueckeroth, F., Thurat, M., Frank, R., Eisert, A., Bitter, E., Wömpner, C., Gogl, L., Merkelbach-Bruse, S., Büttner, R., and Wolf, J.

Published
2016
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36. 1238P - Try - a Phase Ii Study to Evaluate Safety and Efficacy of Combined Trastuzumab and the Hsp90 Inhibitor Auy922 in Advanced Non-Small-Cell Lung Cancer (Nsclc) with Her2 Overexpression or Amplification or Mutation

Author

Nogova, L., Mattonet, C., Scheffler, M., Michels, S., Bos, M., Heukamp, L.C., Schildhaus, H., Fuhr, U., Eberhardt, W.E., Reis, H., Wiesweg, M., Schmid, K.W., Schoch, G., Serke, M., Ko, Y., Schuler, M., Büttner, R., and Wolf, J.

Published
2014
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41. Improvement of platelet dysfunction in chronic myelogenous leukemia following treatment with imatinib: a case report

Author

Scheid Christoph, Kochanek Matthias, Nogova Lucia, Rothe Achim, Shimabukuro-Vornhagen Alexander, and von Bergwelt-Baildon Michael

Subjects
Medicine
Abstract

Abstract Introduction In patients with chronic myeloid leukemia, tyrosine kinase inhibitors suppress the BCR-ABL+ clone and often induce complete molecular remissions. Megakaryocytes in such patients have been shown to be derived from the BCR-ABL+ clone, and abnormal platelet function is frequent in chronic myeloid leukemia. However, little is known about the influence of modern targeted therapy on chronic myeloid leukemia-associated platelet disorders. Case presentation We report the case of a massive hemorrhage in a 32-year-old Caucasian man caused by chronic myeloid leukemia-associated platelet dysfunction, which improved after treatment with imatinib. Conclusion This report demonstrates that platelet dysfunction and bleeding disorder in BCR-ABL+ chronic myeloid leukemia can successfully be treated with imatinib. We suggest the monitoring of platelet function in future studies using imatinib to treat patients with chronic myeloid leukemia.

Published
2011
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42. Rebiopsy in advanced non-small cell lung cancer, clinical relevance and prognostic implications.

Author

Scheffler M, Wiesweg M, Michels S, Nogová L, Kron A, Herold T, Scheel AH, Metzenmacher M, Eberhardt WE, Reis H, Fassunke J, Darwiche K, Aigner C, Schaufler D, Riedel R, Fischer R, Koleczko S, Schildhaus HU, Merkelbach-Bruse S, Schmid KW, Büttner R, Wolf J, and Schuler M

Subjects
ErbB Receptors genetics, Humans, Mutation, Prognosis, Protein-Tyrosine Kinases genetics, Proto-Oncogene Proteins genetics, Carcinoma, Non-Small-Cell Lung drug therapy, Lung Neoplasms pathology
Abstract

Introduction: Rebiopsies of non-small cell lung cancers (NSCLC) are mainly performed to (i) cover the evolution of potentially amenable resistance mechanisms against a targeted therapy, and (ii) to identify new therapeutic targets which were not detected in the initial diagnostic biopsy. Comprehensive systematic analyses evaluating the value of rebiopsies are missing., Methods: Clinical databases from two large comprehensive cancer center networks were queried following prespecified criteria to identify prospectively entered NSCLC cases with at least one rebiopsy at disease progression. Clinicopathological and biomarker findings including multigene sequencing were correlated with clinical outcomes., Results: From a total of 17,477 stage IV NSCLC patients, a cohort of 403 evaluable patients undergoing at least one rebiopsy of a primary tumor or metastasis was retrieved. Changes in biomarker profiles as compared to baseline were observed in 48.9%. In 31.3% of cases, findings of potential therapeutic relevance were revealed, including 18 patients (4.4%) with a targetable marker only detected at rebiopsy. New findings were more frequent (greater than50%) in NSCLC with EGFR/ALK/ROS1 alterations, including mutations of the dominant oncogene, TP53 mutations, and MET or ERBB2 amplifications. Patients undergoing rebiopsy exhibited superior overall survival compared to a control group, irrespective of presence (HR 0.28) or absence (HR 0.20, both p < 0.001) of a therapeutically targetable aberration., Conclusions: Rebiopsies at progression of advanced NSCLC are strongly supported by a high rate of clinically relevant findings. Current clinical practice selects a patient population with exceptional outcomes, which merits further characterization., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Published
2022
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43. Acquired KRAS mutation and loss of low-level MET amplification after durable response to crizotinib in a patient with lung adenocarcinoma.

Author

Riedel R, Michels S, Heydt C, Siemanowski J, Kobe C, Bunck A, Schäfer S, Fischer RN, Scheffler M, Abdulla DSY, Nogová L, Koleczko S, Merkelbach-Bruse S, Büttner R, and Wolf J

Subjects
Adenocarcinoma of Lung genetics, Biomarkers, Tumor genetics, Carcinogenesis genetics, Drug Resistance, Neoplasm genetics, Female, Gene Amplification, Humans, Lung Neoplasms genetics, Middle Aged, Proto-Oncogene Proteins c-met antagonists & inhibitors, Proto-Oncogene Proteins p21(ras) antagonists & inhibitors, Adenocarcinoma of Lung drug therapy, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Crizotinib therapeutic use, Lung Neoplasms drug therapy, Mutation genetics, Proto-Oncogene Proteins c-met genetics, Proto-Oncogene Proteins p21(ras) genetics
Abstract

Objectives: Resistance to tyrosine kinase inhibitor (TKI) therapy occurs inevitably in lung cancer patients with targetable genetic alterations. MET amplification has found to be an oncogenic driver in lung cancer with several reports showing response to MET TKI especially in cases with high-level amplification., Materials and Methods: We report the case of a patient with lung adenocarcinoma harbouring low-level MET amplification and strong MET expression who was treated with crizotinib., Results: The patient developed a durable response to crizotinib. A KRAS mutation and loss of MET amplification was found in a new lesion at time of progression as a potential mechanism of acquired resistance., Conclusion: MET amplification is a continuous biomarker with responses to MET TKI observed even in patients with low-level amplification. KRAS mutations may act as a resistance mechanism to MET inhibition in MET dependent lung cancer., (Copyright © 2019. Published by Elsevier B.V.)

Published
2019
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45. Phase 2 study of rituximab in newly diagnosed stage IA nodular lymphocyte-predominant Hodgkin lymphoma: a report from the German Hodgkin Study Group.

Author

Eichenauer DA, Fuchs M, Pluetschow A, Klimm B, Halbsguth T, Böll B, von Tresckow B, Nogová L, Borchmann P, and Engert A

Subjects
Adult, Aged, Antibodies, Monoclonal, Murine-Derived adverse effects, Antineoplastic Agents adverse effects, Disease-Free Survival, Female, Follow-Up Studies, Humans, Male, Middle Aged, Remission Induction, Rituximab, Young Adult, Antibodies, Monoclonal, Murine-Derived therapeutic use, Antineoplastic Agents therapeutic use, Hodgkin Disease drug therapy, Hodgkin Disease pathology
Abstract

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) accounts for ∼ 5% of Hodgkin lymphoma cases. The disease is characterized by a strong CD20 expression on the malignant cells and a more indolent clinical course compared with classic HL. Anti-CD20 antibody treatment has shown clinical activity in relapsed NLPHL. In this phase 2 trial, we investigated rituximab in newly diagnosed stage IA NLPHL patients. Four weekly applications at 375 mg/m(2) were given. Among the 28 evaluable patients, overall response rate was 100%, 24 patients (85.7%) achieved complete remission, and 4 (14.3%) achieved partial remission. At a median follow-up of 43 months, overall survival was 100%; progression-free survival at 12, 24, and 36 months was 96.4%, 85.3%, and 81.4%, respectively. No grade 3 or 4 toxicity was observed. Although treatment results with rituximab appear inferior compared with radiotherapy and combined-modality approaches in early-stage patients, investigation of anti-CD20 antibody-based combinations in NLPHL is warranted. This study was registered at www.clinicaltrials.gov as #NCT00346684.

Published
2011
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46. Phase 2 study of BACOPP (bleomycin, adriamycin, cyclophosphamide, vincristine, procarbazine, and prednisone) in older patients with Hodgkin lymphoma: a report from the German Hodgkin Study Group (GHSG).

Author

Halbsguth TV, Nogová L, Mueller H, Sieniawski M, Eichenauer DA, Schober T, Nisters-Backes H, Borchmann P, Diehl V, Engert A, and Josting A

Subjects
Aged, Antineoplastic Combined Chemotherapy Protocols toxicity, Bleomycin administration & dosage, Cyclophosphamide, Disease Progression, Doxorubicin administration & dosage, Drug-Related Side Effects and Adverse Reactions, Female, Germany, Hodgkin Disease mortality, Humans, Male, Middle Aged, Prednisone administration & dosage, Procarbazine administration & dosage, Remission Induction, Survival Analysis, Survival Rate, Treatment Outcome, Vincristine administration & dosage, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Hodgkin Disease drug therapy
Abstract

For older patients with early unfavorable or advanced stage Hodgkin lymphoma (HL) the prognosis is much worse than for younger HL patients. We thus developed a new regimen, BACOPP (bleomycin, adriamycin, cyclophosphamide, vincristine, procarbazine, and prednisone), to improve both tolerability and efficacy of treatment for older HL patients. Between 2004 and 2005, 65 patients with early unfavorable or advanced stage HL aged between 60 and 75 years were enrolled in this phase 2 trial. Treatment consisted of 6 to 8 cycles of BACOPP. Residual tumor masses were irradiated. Primary endpoints were feasibility as determined by adherence to protocol and overall response rate. Secondary endpoints included toxicity, freedom from treatment failure, and progression free and overall survival. For the final analysis 60 patients (92%) were eligible; 75% of treatment courses were administered according to protocol. World Health Organization grade 3/4 toxicities occurred in 52 patients. Fifty-one patients (85%) achieved complete remission, 2 (3%) partial remission, and 4 (7%) developed progressive disease. With a median observation time of 33 months, 18 patients died (30%), including 7 treatment-associated deaths. Three patients died before response assessment. Thus, the BACOPP regimen is active in older HL patients but is compromised by a high rate of toxic deaths. This trial was registered at www.clinicaltrials.gov as #NCT00284271.

Published
2010
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47. Osteoblastic response in patients with non-small cell lung cancer with activating EGFR Mutations and bone metastases during treatment with EGFR kinase inhibitors.

Author

Ansén S, Bangard C, Querings S, Gabler F, Scheffler M, Seidel D, Saal B, Zander T, Nogová L, Töpelt K, Markert E, Stoelben E, Ernestus K, Thomas RK, and Wolf J

Subjects
Adenocarcinoma drug therapy, Adenocarcinoma genetics, Adenocarcinoma pathology, Bone Neoplasms genetics, Bone Neoplasms secondary, Carcinoma, Non-Small-Cell Lung genetics, Carcinoma, Non-Small-Cell Lung pathology, ErbB Receptors antagonists & inhibitors, Female, Humans, Lung Neoplasms genetics, Lung Neoplasms pathology, Middle Aged, Prognosis, Survival Rate, Bone Neoplasms drug therapy, Carcinoma, Non-Small-Cell Lung drug therapy, ErbB Receptors genetics, Lung Neoplasms drug therapy, Mutation genetics, Osteoblasts drug effects, Protein Kinase Inhibitors therapeutic use
Published
2010
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48. Downregulation of 18F-FDG uptake in PET as an early pharmacodynamic effect in treatment of non-small cell lung cancer with the mTOR inhibitor everolimus.

Author

Nogová L, Boellaard R, Kobe C, Hoetjes N, Zander T, Gross SH, Dimitrijevic S, Pellas T, Eschner W, Schmidt K, Bangard C, Hayes W, Thomas RK, Dietlein M, Giaccone G, Hoekstra OS, Lammertsma AA, and Wolf J

Subjects
Aged, Biological Transport drug effects, Carcinoma, Non-Small-Cell Lung diagnostic imaging, Carcinoma, Non-Small-Cell Lung drug therapy, Everolimus, Female, Glucose metabolism, Humans, Lung Neoplasms diagnostic imaging, Lung Neoplasms drug therapy, Male, Middle Aged, Pilot Projects, Positron-Emission Tomography, Protein Kinase Inhibitors therapeutic use, Sirolimus pharmacology, Sirolimus therapeutic use, TOR Serine-Threonine Kinases, Time Factors, Carcinoma, Non-Small-Cell Lung metabolism, Fluorodeoxyglucose F18 metabolism, Lung Neoplasms metabolism, Protein Kinase Inhibitors pharmacology, Protein Kinases metabolism, Sirolimus analogs & derivatives
Abstract

Unlabelled: Everolimus downregulates glucose metabolism-associated genes in preclinical models. Inhibition of glucose metabolism measured by (18)F-FDG PET was postulated to serve as a pharmacodynamic marker in everolimus-treated non-small cell lung cancer (NSCLC) patients., Methods: In 8 NSCLC patients treated with everolimus, the percentage change in (18)F-FDG PET uptake (days 8 and 28 relative to baseline) was determined using a variety of summed standardized uptake value (SUV) measures. Both maximum and mean SUVs were used, with normalizations to body surface area and body weight and with and without correcting for plasma glucose levels., Results: In 5 patients, a reduction of (18)F-FDG PET uptake on day 8 was observed with all methods, ranging from -12.8% to -72.2%., Conclusion: These observations demonstrate that inhibition of glucose metabolism is an early effect of everolimus treatment in NSCLC patients and can be assessed using (18)F-FDG PET.

Published
2009
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49. Nodular lymphocyte-predominant Hodgkin lymphoma.

Author

Fuchs M, Eichenauer DA, Nogová L, Diehl V, and Engert A

Subjects
Adult, Antibodies, Monoclonal therapeutic use, Antibodies, Monoclonal, Murine-Derived, Antineoplastic Agents therapeutic use, Combined Modality Therapy, Disease-Free Survival, Female, Hodgkin Disease drug therapy, Hodgkin Disease radiotherapy, Humans, Immunophenotyping, Male, Middle Aged, Prognosis, Recurrence, Rituximab, Hodgkin Disease therapy
Abstract

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare subtype of Hodgkin lymphoma that differs from classic Hodgkin lymphoma (cHL) with respect to histologic and clinical presentation. Because the prognosis of NLPHL in early unfavorable and advanced stages is similar to that of cHL, treatment is similar. In contrast, early favorable-stage NLPHL has a better prognosis than cHL. Thus, NLPHL in early favorable stages might be treated with reduced-intensity programs without compromising cure rates. Because involved-field radiotherapy alone seems to be as effective as extended-field radiotherapy or combined modalities, it has been adopted by the German Hodgkin Study Group and the European Organisation for Research and Treatment of Cancer as the treatment of choice for stage IA NLPHL. Now that efficacy of the monoclonal antibody rituximab has been shown in relapsed NLPHL, its use in the first-line treatment of NLPHL is under investigation.

Published
2008
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50. Biology, clinical course and management of nodular lymphocyte-predominant hodgkin lymphoma.

Author

Nogová L, Rudiger T, and Engert A

Subjects
Age Factors, Disease Management, Hodgkin Disease pathology, Humans, Lymphocytes pathology, Remission Induction methods, Hodgkin Disease therapy
Abstract

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) differs in histological and clinical presentation from classical Hodgkin lymphoma (cHL). The typical morphologic signs of NLPHL are atypical "lymphocytic and histiocytic" (L&H) cells, which are surrounded by a non-neoplastic nodular background of small lymphocytes of B-cell origin. The NLPHL cells are positive for CD45, CD19, CD20, CD22 and CD79a, but lack expression of CD15 and CD30, the typical markers for cHL. NLPHL patients are predominantly of male gender with a median age of 37 years. Patients often present in early stages (63%) and rarely have B-symptoms (9%). Treatment of NLPHL patients using standard Hodgkin lymphoma (HL) protocols leads to complete remission (CR) in more than 95% of patients. Survival and freedom from treatment failure (FFTF) are worse in advanced-stage patients than in early-stage patients. Thus, patients in advanced and in early stages with unfavorable risk factors are treated similarly to cHL patients. In contrast, patients with early-stage NLPHL without risk factors can be sufficiently treated with reduced intensity programs having less severe adverse effects. As a result, treatment of early NLPHL is less clearly defined, including radiotherapy in extended field (EF) or involved field (IF) technique, combined modality treatment, and, more recently, monoclonal antibody rituximab. Watch and wait strategy plays an important role in pediatric oncology to avoid adverse effects associated with therapy.

Published
2006
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