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1. Early switch from run-in treatment with vemurafenib plus cobimetinib to atezolizumab after 3 months leads to rapid loss of tumour control in patients with advanced BRAFV600-positive melanoma: The ImmunoCobiVem phase 2 randomised trial

Author

Livingstone, E., Gogas, H., Kandolf-Sekulovic, L., Meier, F., Eigentler, T.K., Ziemer, M., Terheyden, P.A.M., Gesierich, A.H., Herbst, R.A., Kähler, K.C., Ziogas, D.C., Mijuskovic, Z., Garzarolli, M., Garbe, C., Roesch, A., Ugurel, S., Gutzmer, R., Grob, J.J., Kiecker, F., Utikal, J., Windemuth-Kieselbach, C., Eckhardt, S., Zimmer, L., and Schadendorf, D.

Published
2023
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2. Adjuvant Radiotherapy for pleomorphic dermal sarcoma

Author

Helbig, D., primary, Dapper, H., additional, Kreuter, A., additional, Leiter, U., additional, Sirokay, J., additional, Ziemer, M., additional, Saternus, R., additional, Lang, BM., additional, Huynh, J., additional, Ugurel, S., additional, Gschnell, M., additional, Utikal, J., additional, von Bubnoff, D., additional, and Persa, OD., additional

Published
2024
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4. Sex differences and its impact on treatment outcomes of advanced melanoma in Germany – a DeCOG study on 2032 patients of the multicenter prospective skin cancer registry ADOREG

Author

Leven, A.-S., primary, Peters, T., additional, Rajcsanyi, L.S., additional, Weichenthal, M., additional, Mohr, P., additional, Meier, F., additional, von Wasielewski, I., additional, Gutzmer, R., additional, Utikal, J., additional, Terheyden, P., additional, Herbst, R., additional, Haferkamp, S., additional, Pföhler, C., additional, Leiter, U., additional, Kreuter, A., additional, Gebhardt, C., additional, Weishaupt, C., additional, Grabbe, S., additional, Debus, D., additional, Hassel, J.C., additional, Tasdogan, A., additional, Placke, J.-M., additional, Zimmer, L., additional, Livingstone, E., additional, Schadendorf, D., additional, Roesch, A., additional, Hinney, A., additional, and Ugurel, S., additional

Published
2024
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5. EPH80 Survival and Best Recorded Response (BRR) in Patients With Advanced Merkel Cell Carcinoma (MCC): Analysis of a Prospective German MCC Registry Study (MCC TRIM) of the German Dermatologic Cooperative Oncology Group

Author

Mahmoudpour, S.H., primary, Backer, J.C., additional, Schadendorf, D., additional, Leiter, U., additional, Meier, F., additional, Herbst, R., additional, Grabbe, S., additional, Mohr, P., additional, Sachse, M.M., additional, Pföhler, C., additional, Gerbhardt, C., additional, Ziller, F., additional, Zimmer, L., additional, Boutmy, E., additional, Hoff, S., additional, Verpillat, P., additional, Milano, A.F., additional, Shlaen, M., additional, Fu, C., additional, and Ugurel, S., additional

Published
2023
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11. Dermatofibrosarcoma protuberans

Author

Ugurel, S.

Abstract

Zusammenfassung: Das Dermatofibrosarcoma protuberans (DFSP) gehört zu den seltenen Tumoren der Haut, stellt aber gleichzeitig das häufigste kutane Sarkom dar. Es handelt sich um einen Tumor von fibroblastischer Differenzierung, der langsam, unterminierend und lokal destruierend wächst, aber nur selten metastasiert. Das klinische Bild ist insbesondere bei initialen Befunden oft uncharakteristisch, weshalb die Diagnose in der Regel erst spät und meist durch Biopsie und Histologie gestellt wird. Die Therapie der Wahl ist die komplette chirurgische Exzision des Tumors mit einem Sicherheitsabstand von 2–3 cm. Bei geringeren Sicherheitsabständen besteht ein erhöhtes Risiko für die Ausbildung von Lokalrezidiven. Inoperable oder metastasierte DFSP können bestrahlt werden; die Strahlensensitivität des DFSP gilt als hoch. Nachdem für ca. 90% aller DFSP eine charakteristische Chromosomentranslokation (17:22), einhergehend mit einer Genfusion, beschrieben wurde, die zur Ausbildung einer kontinuierlichen autokrinen Wachstumsstimulation über den PDGFβ-Signalweg führt, existiert die zusätzliche Möglichkeit einer molekular zielgerichteten Therapie. Die erste hierfür zugelassene Substanz ist der Multikinaseinhibitor Imatinib, der in klinischen Studien an ausgedehnten oder metastasierten DFSP eine Remissionsrate von ca. 70% zeigte.

Published
2024
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12. Kutane Nebenwirkungen molekular zielgerichteter Therapien

Author

Pföhler, C. and Ugurel, S.

Abstract

Zusammenfassung: Molekular zielgerichtete Therapien nehmen zunehmend mehr Raum innerhalb der verschiedenen Therapieoptionen für schwerere Erkrankungen, insbesondere für maligne Tumoren, ein. Die zugehörigen Substanzen sind in der Regel hochspezifisch gegen eine oder mehrere molekulare Zielstrukturen gerichtet, unterbinden oder modifizieren auf diese Weise die an diese Zielstruktur angebundenen molekularen Signalwege und führen zu tief greifenden Veränderungen von Proliferation, Aktivierungsstatus und Interaktion der Zielzellen. Diese Eingriffe in hoch spezialisierte molekulare Signalwege haben in der Regel auch sehr spezifische Nebenwirkungen zur Folge, die sich häufig an der Haut der behandelten Patienten manifestieren und so für den Dermatologen ein gänzlich neues Spektrum von Arzneimittelnebenwirkungen aufzeigen. Dieser Übersichtsbeitrag behandelt die kutanen Nebenwirkungen von molekular zielgerichteten Substanzen im Rahmen der Psoriasistherapie sowie im Rahmen der antitumoralen Therapie. Beide Behandlungsfelder umfassen eine Vielzahl von zielgerichteten Therapeutika; behandelt werden für die Psoriasistherapie die Substanzen Alefacept, Efalizumab, Etanercept, Infliximab und Adalimumab; für die Therapie maligner Tumoren die Substanzen Imatinib, Sorafenib, Sunitinib, EGFR-Antagonisten sowie CTLA-4-Antagonisten.

Published
2024
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13. Immune checkpoint inhibition in patients with NRAS mutated and NRAS wild type melanoma: a multicenter DeCOG study on 637 patients from the prospective skin cancer registry ADOREG

Author

Zaremba, A., Mohr, P., Gutzmer, R., Meier, F., Pföhler, C., Weichenthal, M., Terheyden, P., Forschner, A., Leiter, U., Ulrich, J., Utikal, J., Welzel, Julia, Kaatz, M., Gebhardt, C., Herbst, R., Sindrilaru, A., Dippel, E., Sachse, M., Meiss, F., Heinzerling, L., Haferkamp, S., Weishaupt, C., Löffler, H., Kreft, S., Griewank, K., Livingstone, E., Schadendorf, D., Ugurel, S., and Zimmer, L.

Published
2023

15. 787O Adjuvant immunotherapy with nivolumab (NIVO) versus observation in completely resected Merkel cell carcinoma (MCC): Disease-free survival (DFS) results from ADMEC-O, a randomized, open-label phase II trial

Author

Becker, J.C., primary, Ugurel, S., additional, Leiter-Stoppke, U., additional, Meier, F., additional, Gutzmer, R., additional, Haferkamp, S., additional, Zimmer, L., additional, Livingstone, E., additional, Eigentler, T., additional, Hauschild, A., additional, Kiecker, F., additional, Hassel, J.C., additional, Mohr, P., additional, Fluck, M., additional, Thomas, I., additional, Garzarolli, M., additional, Grimmelmann, I., additional, Drexler, K., additional, Eckhardt, S., additional, and Schadendorf, D., additional

Published
2022
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17. Dataset of a retrospective multicenter cohort study on characteristics of immune checkpoint inhibitor-induced encephalitis and comparison with HSV-1 and anti-LGI1 encephalitis.

Author

Müller-Jensen, L, Zierold, S, Versluis, JM, Boehmerle, W, Huehnchen, P, Endres, M, Mohr, R, Compter, A, Blank, CU, Hagenacker, T, Meier, F, Reinhardt, L, Gesierich, A, Salzmann, M, Hassel, JC, Ugurel, S, Zimmer, L, Banks, P, Spain, L, Soon, JA, Enokida, T, Tahara, M, Kähler, KC, Seggewiss-Bernhardt, R, Harvey, C, Long, GV, Schöberl, F, von Baumgarten, L, Hundsberger, T, Schlaak, M, French, LE, Knauss, S, Heinzerling, LM, Müller-Jensen, L, Zierold, S, Versluis, JM, Boehmerle, W, Huehnchen, P, Endres, M, Mohr, R, Compter, A, Blank, CU, Hagenacker, T, Meier, F, Reinhardt, L, Gesierich, A, Salzmann, M, Hassel, JC, Ugurel, S, Zimmer, L, Banks, P, Spain, L, Soon, JA, Enokida, T, Tahara, M, Kähler, KC, Seggewiss-Bernhardt, R, Harvey, C, Long, GV, Schöberl, F, von Baumgarten, L, Hundsberger, T, Schlaak, M, French, LE, Knauss, S, and Heinzerling, LM

Abstract

Over the past decade, cancer immunotherapy with immune checkpoint inhibitors (ICIs) has significantly improved the outcome of many malignancies. However, with the broad use of ICIs, neurological immune related adverse events (irAE) are increasingly recognized. ICI-induced encephalitis (ICI-iE) is a particularly severe irAE, often leading to treatment termination, long-term sequalae or death. Despite its high morbidity and mortality, data on clinical features and diagnostic criteria are limited. We aimed to define clinical, radiologic and laboratory characteristics of ICI-iE and identify factors that discriminate it from anti-leucine-rich glioma-inactivated (anti-LGI)-1 encephalitis and herpes simplex virus (HSV)-1 encephalitis - two alternative causes of encephalitis - to increase the awareness of ICI-iE and improve its diagnosis and management. To that end, we retrospectively collected 30 cases of ICI-iE that were reported to the Side Effect Registry Immuno-Oncology (SERIO) and 46 cases of anti-LGI1 encephalitis or herpes simplex virus (HSV)-1 encephalitis that presented to a large German neurological referral center (Charité Universitätsmedizin Berlin) between January 2015 and September 2021. Signs and symptoms, imaging and electroencephalogram features, laboratory findings and outcome measures were assessed using standardized case report forms as well as patients' medical records and compared between the groups. The data reported here represents the largest primary cohort of patients with ICI-iE to date and the first comparison with other types of encephalitis. As all three disorders - ICI-iE, HSV-1 encephalitis and anti-LGI1 encephalitis - are rare neurological entities, this dataset can be used as a reference in future clinical studies on ICI-induced neurotoxicity, neurological autoimmune disorders, and central nervous system infections.

Published
2022

22. Checkpoint immunotherapy of cutaneous squamous cell carcinoma in patients suffering from chronic lymphocytic leukaemia: divergent outcomes in two men treated with PD‐1 inhibitors

Author

Jansen, P., primary, Lodde, G.C., additional, Wetter, A., additional, Welt, A., additional, Stuschke, M., additional, Dührsen, U., additional, Stoffels, I., additional, Klode, J., additional, Livingstone, E., additional, Zimmer, L., additional, Roesch, A., additional, Hadaschik, E., additional, Griewank, K. G., additional, Schadendorf, D., additional, and Ugurel, S., additional

Published
2021
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25. 1079P Comparison of effectiveness and safety of nivolumab monotherapy or in combination therapy with ipilimumab in therapy-naïve and pretreated patients with advanced melanoma within the German noninterventional study NICO

Author

Gutzmer, R., primary, Eigentler, T., additional, Mohr, P., additional, Weichenthal, M., additional, Dücker, P., additional, Gebhardt, C., additional, Göppner, D., additional, Grimmelmann, I., additional, Haferkamp, S., additional, Kähler, K.C., additional, Meier, F., additional, Pföhler, C., additional, Sickmann, T., additional, Sindrilaru, A., additional, Terheyden, P., additional, Ugurel, S., additional, Ulrich, J., additional, Utikal, J., additional, Weishaupt, C., additional, and Schadendorf, D., additional

Published
2021
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26. High tumour mutational burden and EGFR/MAPK pathway activation are therapeutic targets in metastatic porocarcinoma*

Author

Westphal, D., primary, Garzarolli, M., additional, Sergon, M., additional, Horak, P., additional, Hutter, B., additional, Becker, J.C., additional, Wiegel, M., additional, Maczey, E., additional, Blum, S., additional, Grosche‐Schlee, S., additional, Rütten, A., additional, Ugurel, S., additional, Stenzinger, A., additional, Glimm, H., additional, Aust, D., additional, Baretton, G., additional, Beissert, S., additional, Fröhling, S., additional, Redler, S., additional, Surowy, H., additional, and Meier, F., additional

Published
2021
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34. Response durability after cessation of immune checkpoint inhibitors in patients with metastatic Merkel cell carcinoma: a retrospective multicenter DeCOG study

Author

Stege, H. M., primary, Haist, M., additional, Schultheis, S., additional, Fleischer, M. I., additional, Mohr, P., additional, Ugurel, S., additional, Terheyden, P., additional, Thiem, A., additional, Kiecker, F., additional, Leiter, U., additional, Becker, J. C., additional, Meissner, M., additional, Kleeman, J., additional, Pföhler, C., additional, Hassel, J., additional, Grabbe, S., additional, and Loquai, C., additional

Published
2021
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35. Real World-Daten zur Anwendung von Nivolumab (Nivo) als Monotherapie oder in Kombination mit Ipilimumab (Nivo+Ipi) in der Behandlung des fortgeschrittenen Melanoms: Zwischenergebnisse der nicht-interventionellen Studie NICO [Poster Abstract]

Author

Ugurel, S., Satzger, I., Eigentier, T., Mohr, P., Göppner, D., Herber, M., Herbst, R., Kähler, K. C., Meier, F., Meiß, F., Pföhler, C., Sachse, M. M., Schneider, S. W., Terheyden, P., Ulrich, J., Utikal, J. S., Welzel, Julia, Schadendorf, D., and Gutzmer, R.

Subjects
ddc:610
Published
2020

36. GNAQ and GNA11 mutant nonuveal melanoma: a subtype distinct from both cutaneous and uveal melanoma

Author

Livingstone, E., Zaremba, A., Horn, S., Ugurel, S., Casalini, B., Schlaak, M., Hassel, J. C., Herbst, R., Utikal, J. S., Weide, B., Gutzmer, R., Meier, F., Koelsche, C., Hadaschik, E., Sucker, A., Reis, H., Merkelbach-Bruse, S., Siewert, M., Sahm, F., von Deimling, A., Cosgarea, I., Zimmer, L., Schadendorf, D., Schilling, B., Griewank, K. G., Livingstone, E., Zaremba, A., Horn, S., Ugurel, S., Casalini, B., Schlaak, M., Hassel, J. C., Herbst, R., Utikal, J. S., Weide, B., Gutzmer, R., Meier, F., Koelsche, C., Hadaschik, E., Sucker, A., Reis, H., Merkelbach-Bruse, S., Siewert, M., Sahm, F., von Deimling, A., Cosgarea, I., Zimmer, L., Schadendorf, D., Schilling, B., and Griewank, K. G.

Abstract

Background GNAQ and GNA11 mutant nonuveal melanoma represent a poorly characterized rare subgroup of melanoma with a gene mutation profile similar to uveal melanoma. Objectives To characterize these tumours in terms of clinical behaviour and genetic characteristics. Methods Patients with nonuveal GNAQ/11 mutated melanoma were identified from the prospective multicentre tumour tissue registry ADOREG, Tissue Registry in Melanoma (TRIM) and additional cooperating skin cancer centres. Extensive data on patient, tumour and treatment characteristics were collected retrospectively. Targeted sequencing was used to determine tumour mutational burden. Immunohistochemistry staining was performed for programmed death-ligand 1 and BRCA1-associated protein (BAP)1. Existing whole-exome cutaneous and uveal melanoma data were analysed for mutation type and burden. Results We identified 18 patients with metastatic GNAQ/11 mutant nonuveal melanoma. Tumours had a lower tumour mutational burden and fewer ultraviolet signature mutations than cutaneous melanomas. In addition to GNAQ and GNA11 mutations (nine each), six splicing factor 3b subunit 1 (SF3B1), three eukaryotic translation initiation factor 1A X-linked (EIF1AX) and four BAP1 mutations were detected. In contrast to uveal melanoma, GNAQ/11 mutant nonuveal melanomas frequently metastasized lymphatically and concurrent EIF1AX, SF3B1 and BAP1 mutations showed no apparent association with patient prognosis. Objective response to immunotherapy was poor with only one partial response observed in 10 treated patients (10%). Conclusions Our findings suggest that GNAQ/11 mutant nonuveal melanomas are a subtype of melanoma that is both clinically and genetically distinct from cutaneous and uveal melanoma. As they respond poorly to available treatment regimens, novel effective therapeutic approaches for affected patients are urgently needed. What is already known about this topic? The rare occurrence of GNAQ/11 mutations in nonuveal melanom

Published
2020

37. Agranulocytosis with Immune Checkpoint-Blockade - a retrospective, multicenter Evaluation

Author

Zaremba, A., Martaki, A., Salzmann, M., Baroudjian, B., Sachse, M. M., Gesierich, A., Reinhardt, L., Meier, F., Hassel, J. C., Ugurel, S., Roesch, A., Schadendorf, D., Livingstone, E., Broeckelmann, P., Kramer, R., Heinzerling, L., Zimmer, L., Zaremba, A., Martaki, A., Salzmann, M., Baroudjian, B., Sachse, M. M., Gesierich, A., Reinhardt, L., Meier, F., Hassel, J. C., Ugurel, S., Roesch, A., Schadendorf, D., Livingstone, E., Broeckelmann, P., Kramer, R., Heinzerling, L., and Zimmer, L.

Published
2020

39. SERIO - Side Effect Registry Immuno-Oncology Side Effect Registry for rare, severe and complex Side Effects of Immunotherapy

Author

Kramer, R., Mentzer, D., Erdmann, M., Knauss, S., Broeckelmann, P. J., Hassel, J. C., Ugurel, S., Pavel, M., Nickel, F. T., Landendinger, M., Fuchs, F., Meidenbauer, N., Jefremow, A., Manger, B., Gutzmer, R., Loquai, C., Kaehler, K., Zimmer, L., Berking, C., Keller-Stanislawski, B., Heinzerling, L., Kramer, R., Mentzer, D., Erdmann, M., Knauss, S., Broeckelmann, P. J., Hassel, J. C., Ugurel, S., Pavel, M., Nickel, F. T., Landendinger, M., Fuchs, F., Meidenbauer, N., Jefremow, A., Manger, B., Gutzmer, R., Loquai, C., Kaehler, K., Zimmer, L., Berking, C., Keller-Stanislawski, B., and Heinzerling, L.

Published
2020

42. Preclinical and clinical assessment of immune checkpoint inhibitor-associated left ventricular dysfunction

Author

Michel, L, primary, Hendgen-Cotta, U.B, additional, Mincu, R.I, additional, Helfrich, I, additional, Korste, S, additional, Mrotzek, S.M, additional, Rischpler, C, additional, Herrmann, K, additional, Ugurel, S, additional, Zimmer, L, additional, Coman, C, additional, Ahrends, R, additional, Schadendorf, D, additional, Rassaf, T, additional, and Totzeck, M, additional

Published
2020
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49. Dacarbazine (DTIC) versus vaccination with autologous peptide-pulsed dendritic cells (DC) in first-line treatment of patients with metastatic melanoma: a randomized phase III trial of the DC study group of the DeCOG

Author

Schadendorf, D., Ugurel, S., Schuler-Thurner, B., Nestle, F.O., Enk, A., Bröcker, E.-B., Grabbe, S., Rittgen, W., Edler, L., Sucker, A., Zimpfer-Rechner, C., Berger, T., Kamarashev, J., Burg, G., Jonuleit, H., Tüttenberg, A., Becker, J.C., Keikavoussi, P., Kämpgen, E., and Schuler, G.

Published
2006
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