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Klinische Forschung - Neuroblastomstudie

Studienbüro der deutschlandweiten Therapiestudien für Kinder und Jugendliche mit Neuroblastom

Arbeitgruppe

Prof. Dr. Frank Berthold (Studienleiter)
Prof. Dr. Thorsten Simon (Studienkoordinator)
Dr. Barbara Hero (Studienkoordinatorin)

Kontakt

Uniklinik Köln
Klinik für Kinder- und Jugendmedizin
Abteilung für Kinderonkologie und -hämatologie
Kerpener Str. 62
50937 Köln

Telefon: +49 221 478-6853
Telefax: +49 221 478-6851
E-Mail: neuroblastomstudie@uk-koeln.de 

Mitarbeiter

Dr. Maike Reisberg, Studienärztin
Martina Breuer, Studiensekretariat
Monika Schmitz, Studiensekretariat

Schwerpunkte

  • Konzeption und Durchführung von Phase II und Phase III Studien
  • Datenbankpflege
  • prospektive und retrospektive Datenanalyse
  • Publikation von Studienergebnisse
  • internationale Kooperation im Rahmen der INRG-Datenbank
  • klinische Daten werden pseudonymisiert Forschern für die Auswertung ihrer Ergebnisse zur Verfügung gestellt

Aufgaben des Studienbüros

  • Erfassung und Auswertung der Daten von Patienten mit Neuroblastom oder Ganglioneurom
  • Entwicklung neuer Therapieansätze und Studienprotokolle
  • internationale Kooperation
  • Beratung der behandelnden Kliniken auf Wunsch 

Studienprotokoll NB2004 / NB2004-HR

(Studienbeginn Pilotphase: 01.10.2004; Studienstart 01.01.2007)

Das Studienprotokoll kann behandelnden Ärzten auf Anfrage zur Verfügung gestellt werden (neuroblastomstudie@uk-koeln.de).

Rezidivansätze

In Abhängigkeit von der Ausdehnung des Rezidivs, dem Zeitpunkt des Auftretens und der Molekulargenetik stehen unterschiedliche Strategien zur Auswahl. Die Studienzentrale steht hier gerne beratend zur Verfügung.

Randomisierungsbögen NB2004

Telefon: +49 221 478-6853
Telefax: +49 221 478-6851
nach 15.00 Uhr und am Wochenende (08.00 Uhr bis 18.00 Uhr):
Mobil: 0175  3829512

Die Dokumentationsbögen der Stude NB2004/ NB2004-HR finden Sie hier

Enge Zusammenarbeit mit:

  • Kinderkrebsregister Mainz
  • Kinderonkologische Einrichtungen in Deutschland und der Schweiz
  • angeschlossene molekulargenetische Laboratorien
  • nationale und internationale Forschungsgruppen 

Publikationen

  1. Wachowiak, R., H. Till, R. Metzger, U. Bierbach, T. Simon, B. Sattler, T. Aigner, O. Sabri, and R. Kluge, Residual lymph node metastasis in stage 4 neuroblastoma-advantage of radio-guided surgery? Pediatr Hematol Oncol, 2010. 27(6): p. 471-5.
  2. Sudbrock, F., M. Schmidt, T. Simon, W. Eschner, F. Berthold, and H. Schicha, Dosimetry for 131I-MIBG therapies in metastatic neuroblastoma, phaeochromocytoma and paraganglioma. Eur J Nucl Med Mol Imaging, 2010. 37(7): p. 1279-90.
  3. Simon, T., F. Berthold, A. Borkhardt, B. Kremens, B. De Carolis, and B. Hero, Treatment and outcomes of patients with relapsed, high-risk neuroblastoma: Results of German trials. Pediatr Blood Cancer, 2010.
  4. Schmidt, M., R.P. Baum, T. Simon, and R. Howman-Giles, Therapeutic nuclear medicine in pediatric malignancy. Q J Nucl Med Mol Imaging, 2010. 54(4): p. 411-28.
  5. Oberthuer, A., B. Hero, F. Berthold, D. Juraeva, A. Faldum, Y. Kahlert, S. Asgharzadeh, R. Seeger, P. Scaruffi, G.P. Tonini, I. Janoueix-Lerosey, O. Delattre, G. Schleiermacher, J. Vandesompele, J. Vermeulen, F. Speleman, R. Noguera, M. Piqueras, J. Benard, A. Valent, S. Avigad, I. Yaniv, A. Weber, H. Christiansen, R.G. Grundy, K. Schardt, M. Schwab, R. Eils, P. Warnat, L. Kaderali, T. Simon, B. Decarolis, J. Theissen, F. Westermann, B. Brors, and M. Fischer, Prognostic impact of gene expression-based classification for neuroblastoma. J Clin Oncol, 2010. 28(21): p. 3506-15.
  6. De Preter, K., J. Vermeulen, B. Brors, O. Delattre, A. Eggert, M. Fischer, I. Janoueix-Lerosey, C. Lavarino, J.M. Maris, J. Mora, A. Nakagawara, A. Oberthuer, M. Ohira, G. Schleiermacher, A. Schramm, J.H. Schulte, Q. Wang, F. Westermann, F. Speleman, and J. Vandesompele, Accurate outcome prediction in neuroblastoma across independent data sets using a multigene signature. Clin Cancer Res, 2010. 16(5): p. 1532-41.
  7. Ackermann, S., F. Goeser, J.H. Schulte, A. Schramm, V. Ehemann, B. Hero, A. Eggert, F. Berthold, and M. Fischer, Polo-like kinase 1 is a therapeutic target in high-risk neuroblastoma. Clin Cancer Res, 2010.
  8. Voth, H., A. Oberthuer, T. Simon, Y. Kahlert, F. Berthold, and M. Fischer, Co-regulated expression of HAND2 and DEIN by a bidirectional promoter with asymmetrical activity in neuroblastoma. BMC Mol Biol, 2009. 10: p. 28.
  9. Vermeulen, J., K. De Preter, A. Naranjo, L. Vercruysse, N. Van Roy, J. Hellemans, K. Swerts, S. Bravo, P. Scaruffi, G.P. Tonini, B. De Bernardi, R. Noguera, M. Piqueras, A. Canete, V. Castel, I. Janoueix-Lerosey, O. Delattre, G. Schleiermacher, J. Michon, V. Combaret, M. Fischer, A. Oberthuer, P.F. Ambros, K. Beiske, J. Benard, B. Marques, H. Rubie, J. Kohler, U. Potschger, R. Ladenstein, M.D. Hogarty, P. McGrady, W.B. London, G. Laureys, F. Speleman, and J. Vandesompele, Predicting outcomes for children with neuroblastoma using a multigene-expression signature: a retrospective SIOPEN/COG/GPOH study. Lancet Oncol, 2009. 10(7): p. 663-71.
  10. Theissen, J., M. Boensch, R. Spitz, D. Betts, S. Stegmaier, H. Christiansen, F. Niggli, F. Schilling, M. Schwab, T. Simon, F. Westermann, F. Berthold, and B. Hero, Heterogeneity of the MYCN oncogene in neuroblastoma. Clin Cancer Res, 2009. 15(6): p. 2085-90.
  11. Stutterheim, J., A. Gerritsen, L. Zappeij-Kannegieter, B. Yalcin, R. Dee, M.M. van Noesel, F. Berthold, R. Versteeg, H.N. Caron, C.E. van der Schoot, and G.A. Tytgat, Detecting minimal residual disease in neuroblastoma: the superiority of a panel of real-time quantitative PCR markers. Clin Chem, 2009. 55(7): p. 1316-26.
  12. Oehme, I., H.E. Deubzer, D. Wegener, D. Pickert, J.P. Linke, B. Hero, A. Kopp-Schneider, F. Westermann, S.M. Ulrich, A. von Deimling, M. Fischer, and O. Witt, Histone deacetylase 8 in neuroblastoma tumorigenesis. Clin Cancer Res, 2009. 15(1): p. 91-9.
  13. Oberthuer, A., J. Theissen, F. Westermann, B. Hero, and M. Fischer, Molecular characterization and classification of neuroblastoma. Future Oncol, 2009. 5(5): p. 625-39.
  14. Nevo, I., A. Oberthuer, E. Botzer, O. Sagi-Assif, S. Maman, M. Pasmanik-Chor, N. Kariv, M. Fischer, I. Yron, and I.P. Witz, Gene-expression-based analysis of local and metastatic neuroblastoma variants reveals a set of genes associated with tumor progression in neuroblastoma patients. Int J Cancer, 2009. 126(7): p. 1570-81.
  15. Monclair, T., G.M. Brodeur, P.F. Ambros, H.J. Brisse, G. Cecchetto, K. Holmes, M. Kaneko, W.B. London, K.K. Matthay, J.G. Nuchtern, D. von Schweinitz, T. Simon, S.L. Cohn, and A.D. Pearson, The International Neuroblastoma Risk Group (INRG) staging system: an INRG Task Force report. J Clin Oncol, 2009. 27(2): p. 298-303.
  16. Kaatsch, P., I. Reinisch, C. Spix, F. Berthold, G. Janka-Schaub, A. Mergenthaler, . Michaelis, and M. Blettner, Case-control study on the therapy of childhood cancer and the occurrence of second malignant neoplasms in Germany. Cancer Causes Control, 2009. 20(6): p. 965-80.
  17. Fischer, M., T. Bauer, A. Oberthur, B. Hero, J. Theissen, M. Ehrich, R. Spitz, R. Eils, F. Westermann, B. Brors, R. Konig, and F. Berthold, Integrated genomic profiling identifies two distinct molecular subtypes with divergent outcome in neuroblastoma with loss of chromosome 11q. Oncogene, 2009. 29(6): p. 865-75.
  18. Cohn, S.L., A.D. Pearson, W.B. London, T. Monclair, P.F. Ambros, G.M. Brodeur, A. Faldum, B. Hero, T. Iehara, D. Machin, V. Mosseri, T. Simon, A. Garaventa, V. Castel, and K.K. Matthay, The International Neuroblastoma Risk Group (INRG) classification system: an INRG Task Force report. J Clin Oncol, 2009. 27(2): p. 289-97.
  19. Benz-Bohm, G., B. Hero, A. Gossmann, T. Simon, F. Korber, and F. Berthold, Focal nodular hyperplasia of the liver in longterm survivors of neuroblastoma: how much diagnostic imaging is necessary? Eur J Radiol, 2009. 74(3): p. e1-5.
  20. Wilken, B., M. Baumann, C.G. Bien, B. Hero, K. Rostasy, and F. Hanefeld, Chronic relapsing opsoclonus-myoclonus syndrome: combination of cyclophosphamide and dexamethasone pulses. Eur J Paediatr Neurol, 2008. 12(1): p. 51-5.
  21. Westermann, F., D. Muth, A. Benner, T. Bauer, K.O. Henrich, A. Oberthuer, B. Brors, T. Beissbarth, J. Vandesompele, F. Pattyn, B. Hero, R. Konig, M. Fischer, and M. Schwab, Distinct transcriptional MYCN/c-MYC activities are associated with spontaneous regression or malignant progression in neuroblastomas. Genome Biol, 2008. 9(10): p. R150.
  22. Stutterheim, J., A. Gerritsen, L. Zappeij-Kannegieter, I. Kleijn, R. Dee, L. Hooft, M.M. van Noesel, M. Bierings, F. Berthold, R. Versteeg, H.N. Caron, C.E. van der Schoot, and G.A. Tytgat, PHOX2B is a novel and specific marker for minimal residual disease testing in neuroblastoma. J Clin Oncol, 2008. 26(33): p. 5443-9.
  23. Simon, T., B. Hero, G. Benz-Bohm, D. von Schweinitz, and F. Berthold, Review of image defined risk factors in localized neuroblastoma patients: Results of the GPOH NB97 trial. Pediatr Blood Cancer, 2008. 50(5): p. 965-9.
  24. Schmidt, M., T. Simon, B. Hero, H. Schicha, and F. Berthold, The prognostic impact of functional imaging with (123)I-mIBG in patients with stage 4 neuroblastoma >1 year of age on a high-risk treatment protocol: results of the German Neuroblastoma Trial NB97. Eur J Cancer, 2008. 44(11): p. 1552-8.
  25. Hero, B., Berthold, F., Neuroblastoma. Leitlinien Kinderheilkunde und Jugendmedizin, ed. D. Reinhardt. 2008: Urban & Fischer. L5 1-5.
  26. Hero, B., Simon, T., Spitz, R., Ernestus, K., Gnekow, A., Scheel-Walter, HG., Schwabe, D., Schilling, FH., Benz-Bohm, G., Berthold, F., Localized infant neuroblastomas often show spontaneous regression: Results of the prospective trials NB95-S and NB97. J Clin Oncol, 2008. 26(9): p. 1504-1509.
  27. Franzius, C., M. Schmidt, B. Hero, T. Pfluger, and K. Hahn, [Procedure guidelines for MIBG-scintigraphy in children]. Nuklearmedizin, 2008. 47(3): p. 132-8.
  28. Ertle, F., W. Behnisch, N.A. Al Mulla, M. Bessisso, D. Rating, G. Mechtersheimer, B. Hero, and A.E. Kulozik, Treatment of neuroblastoma-related opsoclonus-myoclonus-ataxia syndrome with high-dose dexamethasone pulses. Pediatr Blood Cancer, 2008. 50(3): p. 683-7.
  29. Voth, H., A. Oberthuer, T. Simon, Y. Kahlert, F. Berthold, and M. Fischer, Identification of DEIN, a novel gene with high expression levels in stage IVS neuroblastoma. Mol Cancer Res, 2007. 5(12): p. 1276-84.
  30. Simon, T., A. Langler, U. Harnischmacher, M.C. Fruhwald, N. Jorch, A. Claviez, F. Berthold, and B. Hero, Topotecan, cyclophosphamide, and etoposide (TCE) in the treatment of high-risk neuroblastoma. Results of a phase-II trial. J Cancer Res Clin Oncol, 2007.
  31. Simon, T., A. Langler, F. Berthold, T. Klingebiel, and B. Hero, Topotecan and etoposide in the treatment of relapsed high-risk neuroblastoma: results of a phase 2 trial. J Pediatr Hematol Oncol, 2007. 29(2): p. 101-6.
  32. Opel, D., C. Poremba, T. Simon, K.M. Debatin, and S. Fulda, Activation of Akt predicts poor outcome in neuroblastoma. Cancer Res, 2007. 67(2): p. 735-45.
  33. Oberthuer, A., P. Warnat, Y. Kahlert, F. Westermann, R. Spitz, B. Brors, B. Hero, R. Eils, M. Schwab, F. Berthold, and M. Fischer, Classification of neuroblastoma patients by published gene-expression markers reveals a low sensitivity for unfavorable courses of MYCN non-amplified disease. Cancer Lett, 2007. 250(2): p. 250-267.
  34. Jensen, M. and F. Berthold, Targeting the neural cell adhesion molecule in cancer. Cancer Lett, 2007. 258(1): p. 9-21.
  35. Jensen, M., Klehr, M., Vogel, A., Schmitz, S., Tawadros, S., Mühlenhoff, M., Plück, A., Fischer, T., Schomäcker, K., Schultze, JL., Berthold, F., One step generation of fully chimeric antibodies using Cy1-and Ck mutant mice. J Immunother, 2007. 30: p. 338-349.
  36. Berthold, F., Neuroblastoma, in Therapiekonzepte Onkologie, S. Seeber, Schütte, J., Editor. 2007, Springer: Heidelberg. p. 1023-1030.
  37. Sudbrock, F., W. Eschner, M. Schmidt, T. Simon, B. Hero, and H. Schicha, [Dosimetry for therapeutic treatment of neuroblastoma by 131I-mIBG]. Nuklearmedizin, 2006. 45(6): p. 254-61.
  38. Spitz, R., A. Oberthuer, M. Zapatka, B. Brors, B. Hero, K. Ernestus, J. Oestreich, M. Fischer, T. Simon, and F. Berthold, Oligonucleotide array-based comparative genomic hybridization (aCGH) of 90 neuroblastomas reveals aberration patterns closely associated with relapse pattern and outcome. Genes Chromosomes Cancer, 2006. 45(12): p. 1130-42.
  39. Spitz, R., B. Hero, T. Simon, and F. Berthold, Loss in chromosome 11q identifies tumors with increased risk for metastatic relapses in localized and 4S neuroblastoma. Clin Cancer Res, 2006. 12(11 Pt 1): p. 3368-73.
  40. Spitz, R., D.R. Betts, T. Simon, M. Boensch, J. Oestreich, F.K. Niggli, K. Ernestus, F. Berthold, and B. Hero, Favorable outcome of triploid neuroblastomas: a contribution to the special oncogenesis of neuroblastoma. Cancer Genet Cytogenet, 2006. 167(1): p. 51-6.
  41. Simon, T., R. Spitz, B. Hero, F. Berthold, and A. Faldum, Risk estimation in localized unresectable single copy MYCN neuroblastoma by the status of chromosomes 1p and 11q. Cancer Lett, 2006. 237(2): p. 215-22.
  42. Simon, T., B. Hero, R. Bongartz, M. Schmidt, R.P. Muller, and F. Berthold, Intensified external-beam radiation therapy improves the outcome of stage 4 neuroblastoma in children > 1 year with residual local disease. Strahlenther Onkol, 2006. 182(7): p. 389-94.
  43. Schmidt, M., T. Simon, B. Hero, W. Eschner, M. Dietlein, F. Sudbrock, R. Bongartz, F. Berthold, and H. Schicha, Is there a benefit of 131 I-MIBG therapy in the treatment of children with stage 4 neuroblastoma? A retrospective evaluation of The German Neuroblastoma Trial NB97 and implications for The German Neuroblastoma Trial NB2004. Nuklearmedizin, 2006. 45(4): p. 145-51; quiz N39-40.
  44. Rostasy, K., B. Wilken, M. Baumann, K. Muller-Deile, I. Bieber, J. Gartner, P. Moller, P. Angelini, and B. Hero, High dose pulsatile dexamethasone therapy in children with opsoclonus-myoclonus syndrome. Neuropediatrics, 2006. 37(5): p. 291-5.
  45. Otto, C., M. Jensen, M. Dietlein, T. Fischer, M. Schmidt, S. Tawadros, S.M. Borner, S.A. Weber, R. Spitz, W. Bloch, F. Berthold, H. Schicha, and K. Schomacker, Localization of 131I-labelled monoclonal antibody ERIC1 in a subcutaneous xenograft model of neuroblastoma in SCID mice. Nucl Med Commun, 2006. 27(2): p. 171-8.
  46. Oberthuer, A., F. Berthold, P. Warnat, B. Hero, Y. Kahlert, R. Spitz, K. Ernestus, R. Konig, S. Haas, R. Eils, M. Schwab, B. Brors, F. Westermann, and M. Fischer, Customized oligonucleotide microarray gene expression-based classification of neuroblastoma patients outperforms current clinical risk stratification. J Clin Oncol, 2006. 24(31): p. 5070-8.
  47. Hufnagel, M., A. Claviez, N. Czech, M. Schmidt, and B. Hero, Neuroblastoma stage 4S with 123I-MIBG-positive bone marrow involvement. Pediatr Blood Cancer, 2006. 46(2): p. 264-5.
  48. Hero, B., Berthold, F., Neuroblastom, in Kurzgefasste interdisziplinäre Leitlinien 2006, A. Garbe, Beckmann, Editor. 2006, Zuckschwerdt Verlag. p. 508-511.
  49. Fulda, S., C. Poremba, B. Berwanger, S. Hacker, M. Eilers, H. Christiansen, B. Hero, and K.M. Debatin, Loss of caspase-8 expression does not correlate with MYCN amplification, aggressive disease, or prognosis in neuroblastoma. Cancer Res, 2006. 66(20): p. 10016-23.
  50. Fischer, M., A. Oberthuer, B. Brors, Y. Kahlert, M. Skowron, H. Voth, P. Warnat, K. Ernestus, B. Hero, and F. Berthold, Differential expression of neuronal genes defines subtypes of disseminated neuroblastoma with favorable and unfavorable outcome. Clin Cancer Res, 2006. 12(17): p. 5118-28.
  51. Wolfl, M., A.A. Jungbluth, F. Garrido, T. Cabrera, S. Meyen-Southard, R. Spitz, K. Ernestus, and F. Berthold, Expression of MHC class I, MHC class II, and cancer germline antigens in neuroblastoma. Cancer Immunol Immunother, 2005. 54(4): p. 400-6.
  52. Simon, T., B. Hero, A. Faldum, R. Handgretinger, M. Schrappe, D. Niethammer, and F. Berthold, Infants with stage 4 neuroblastoma: the impact of the chimeric anti-GD2-antibody ch14.18 consolidation therapy. Klin Padiatr, 2005. 217(3): p. 147-52.
  53. Simon, T., [Neuroblastoma]. Urologe A, 2005. 44(5): p. 543-54; 555.
  54. Oberthuer, A., M. Skowron, R. Spitz, Y. Kahlert, F. Westermann, K. Mehler, F. Berthold, and M. Fischer, Characterization of a complex genomic alteration on chromosome 2p that leads to four alternatively spliced fusion transcripts in the neuroblastoma cell lines IMR-5, IMR-5/75 and IMR-32. Gene, 2005. 363: p. 41-50.
  55. Matthay, K.K., F. Blaes, B. Hero, D. Plantaz, P. De Alarcon, W.G. Mitchell, M. Pike, and V. Pistoia, Opsoclonus myoclonus syndrome in neuroblastoma a report from a workshop on the dancing eyes syndrome at the advances in neuroblastoma meeting in Genoa, Italy, 2004. Cancer Lett, 2005. 228(1-2): p. 275-82.
  56. London, W.B., L. Boni, T. Simon, F. Berthold, C. Twist, M.L. Schmidt, R.P. Castleberry, K.K. Matthay, S.L. Cohn, and B. De Bernardi, The role of age in neuroblastoma risk stratification: the German, Italian, and children's oncology group perspectives. Cancer Lett, 2005. 228(1-2): p. 257-66.
  57. Ladenstein, R., Berthold, F., Ambros, I., Ambros, P., Neuroblastome, in Pädiatrische Hämatologie und Onkologie, H. Gadner, Gaedicke, G., Niemeyer, R., Ritter, J., Editor. 2005, Springer Verlag. p. 829-846.
  58. Hero, B., Berthold, F., Neuroblastoma, in Leitlinien Kinderheilkunde und Jugendmedizin, D. Reinhardt, Editor. 2005, Urban & Fischer. p. L5 1-5.
  59. Fischer, M., Oberthuer, A., von Schweinitz, D., Simon, T., Das Neuroblastom. Der Onkologe, 2005. 11: p. 1054-1064.
  60. Eich, H.T., R.P. Muller, O. Micke, M. Kocher, F. Berthold, and B. Hero, Esthesioneuroblastoma in childhood and adolescence. Better prognosis with multimodal treatment? Strahlenther Onkol, 2005. 181(6): p. 378-84.
  61. De Bernardi, B., W. Balwierz, J. Bejent, S.L. Cohn, M.L. Garre, T. Iehara, D. Plantaz, T. Simon, P. Angelini, A. Cama, W.B. London, K. Kramer, H.M. Katzenstein, P. Tortori-Donati, A. Rossi, G.J. D'Angio, and A.E. Evans, Epidural compression in neuroblastoma: Diagnostic and therapeutic aspects. Cancer Lett, 2005. 228(1-2): p. 283-99.
  62. Blaes, F., V. Fuhlhuber, M. Korfei, M. Tschernatsch, W. Behnisch, K. Rostasy, B. Hero, M. Kaps, and K.T. Preissner, Surface-binding autoantibodies to cerebellar neurons in opsoclonus syndrome. Ann Neurol, 2005. 58(2): p. 313-7.
  63. Berthold, F., J. Boos, S. Burdach, R. Erttmann, G. Henze, J. Hermann, T. Klingebiel, B. Kremens, F.H. Schilling, M. Schrappe, T. Simon, and B. Hero, Myeloablative megatherapy with autologous stem-cell rescue versus oral maintenance chemotherapy as consolidation treatment in patients with high-risk neuroblastoma: a randomised controlled trial. Lancet Oncol, 2005. 6(9): p. 649-58.
  64. Berthold, F., Neuroblastom, in Kompendium Internistische Onkologie, H. Schmoll, Possinger, Editor. 2005, Springer Verlag. p. 843-846.
  65. Berthold, F., Simon, T., Clinical Presentation, in Neuroblastoma, N.K. Cheung, Cohn, S.L., Editor. 2005, Springer Verlag. p. 63-85.

 

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