Aktuelle Neurologie 2010; 37(9): 454-460
DOI: 10.1055/s-0030-1265968
Neues in der Neurologie

© Georg Thieme Verlag KG Stuttgart · New York

Was gibt es Neues in der Neuroonkologie

What is New in Neurooncology?W.  Wick1 , P.  Roth2 , A.  Wick1 , M.  Weller2
  • 1Neurologische Klinik & Nationales Zentrum für Tumorerkrankungen, Abteilung Neuroonkologie, Universitätsklinikum Heidelberg
  • 2Klinik für Neurologie, UniversitätsSpital Zürich, Schweiz
Further Information

Publication History

Publication Date:
21 December 2010 (online)

Zusammenfassung

Wegweisende, häufig von Neurologen koordinierte Studien erlauben einen vorsichtig optimistischen Ausblick auf die Entwicklung der Neuroonkologie. Erkenntnisse wurden dabei im Bereich der anaplastischen Gliome, der primären ZNS-Lymphome sowie der Hirnmetastasen durch die Beantwortung von Therapieoptimierungsfragen zur Rolle der Radiotherapie gewonnen. Weitere Neuerungen betreffen die gemeinsam mit den Neuropathologen verfolgte Einführung molekularer Faktoren in die Entwicklung von Studien bei anaplastischen Gliomen und Glioblastomen und in die Klassifikation der Hirntumoren. Diese Fortschritte wurde durch die Durchführung kontrollierter Studien und die konsequente molekulare Auswertung von Tumorgeweben erzielt. Im Gegensatz dazu hinterlassen viele vermeintlich innovative, aber unkontrollierte und wegen fehlenden Biobankings auch nicht nachhaltig angelegte Studien mehr Fragen als Antworten, sowie ein Strohfeuer anstelle rationaler akademischer Therapieentwicklung. Zusammenfassend wurde dadurch Fortschritt erzielt, dass grundsätzliche Studienfragen gestellt und nicht nur Substanzen getestet wurden. Die relevanten Studien sind kontrolliert und beinhalten verpflichtende zentrale Strukturen wie eine Referenzpathologie, -radiologie und Gewebebanken.

Abstract

Several clinical trials that were mainly coordinated by neurologists allow a careful but optimistic view on the future of neurooncology. New insights have been gained particularly in anaplastic glioma, primary CNS lymphoma as well as brain metastases by answering the basic question about the optimal place for radiotherapy in the treatment of these diseases. Another important development concerns the introduction of molecular factors into the inclusion criteria of clinical trials as well as possibly into the so far merely histopathological WHO classification of brain tumours. These advances are attributed to the conduct of controlled trials and systematic evaluation of tumour tissue for molecular parameters. In contrast, many seemingly innovative but uncontrolled trials produce more questions than answers and are regarded as short-lived opportunities rather than a rational academic drug development. The lack of biobanking in most of these trials will also not allow future insights with increasing knowledge about the molecular pathology of the disease. Hence, important lessons learned in neurooncology are to dare to pose real questions rather than to merely test compounds, to appreciate the value of controls and the to accept the necessity of central structures, including, but not limited to central pathology, radiology and biobanking.

Literatur

  • 1 Louis D N, Ohgaki H, Wiestler O D. et al . The 2007 WHO classification of tumours of the central nervous system.  Acta Neuropathol. 2007;  114 97-109
  • 2 Kouwenhoven M CM, Gorlia T, Kros J M. et al . Molecular analysis of anaplastic oligodendroglial tumors in a prospective randomized study: A report from EORTC study 26951.  Neuro-oncol. 2009;  11 737-746
  • 3 Van den Bent M J, Carpentier A F, Brandes A A. et al . Adjuvant procarbazine, lomustine, and vincristine improves progression-free survival but not overall survival in newly diagnosed anaplastic oligodendrogliomas and oligoastrocytomas: a randomized European Organisation for Research and Treatment of Cancer phase III trial.  J Clin Oncol. 2006;  24 2715-2722
  • 4 Van den Bent M J, Dubbink H J, Sanson M. et al . MGMT promoter methylation is prognostic but not predictive for outcome to adjuvant PCV chemotherapy in anaplastic oligodendroglial tumors: a report from EORTC Brain Tumor Group study 26951.  J Clin Oncol. 2009;  27 5881-5886
  • 5 Cairncross G, Berkey B, Shaw E. et al . Phase III trial of chemotherapy plus radiotherapy compared with radiotherapy alone for pure and mixed anaplastic oligodendroglioma: Intergroup Radiation Therapy Oncology Group Trial 9402.  J Clin Oncol. 2006;  24 2707-2714
  • 6 Wick W, Hartmann C, Engel C. et al., for the Neurooncology Working Group (NOA) of the German Cancer Society . NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with PCV or temozolomide.  J Clin Oncol. 2009;  27 5874-5880
  • 7 Keime-Guibert F, Chinot O, Taillandier L. et al . Radiotherapy for glioblastoma in the elderly.  N Engl J Med. 2007;  356 1527-1535
  • 8 Meckling S, Dold O, Forsyth P AJ. et al . Malignant supratentorial glioma in the elderly: is radiotherapy useful?.  Neurology. 1996;  47 901-905
  • 9 Glantz M, Chamberlain M, Liu Q. et al . Temozolomide as an alternative to irradiation for elderly patients with newly diagnosed malignant glioma.  Cancer. 2003;  97 2262-2266
  • 10 Wick W, Steinbach J P, Küker W M. et al . One week on / one week off: a novel active regimen of temozolomide for recurrent glioblastoma.  Neurology. 2004;  62 2113-2115
  • 11 Wick A, Felsberg J, Steinbach J P. et al . Efficacy and tolerability of Temozolomide in an one week on / one week off regimen in patients with recurrent glioma.  J Clin Oncol. 2007;  25 3357-3361
  • 12 Wick W, Engel C, Combs S E. et al . NOA-08 randomized phase III trial of 1-week-on / 1-week-off temozolomide versus involved field radiotherapy in elderly (older than age 65) patients with newly diagnosed anaplastic astrocytoma or glioblastoma (Methusalem).  J Clin Oncol. 2010;  28 7 s (suppl abstr. LBA2001)
  • 13 Roa W, Brasher P M, Bauman G. et al . Abbreviated course of radiation therapy in older patients with glioblastoma multiforme: a prospective randomized clinical trial.  J Clin Oncol. 2004;  22 1583-1588
  • 14 Malmstrom A, Grønberg B H, Stupp R. et al . Glioblastoma (GBM) in elderly patients: A randomized phase III trial comparing survival in patients treated with 6-week radiotherapy (RT) versus hypofractionated RT over 2 weeks versus temozolomide single-agent chemotherapy (TMZ).  J Clin Oncol. 2010;  28 7s (suppl abstr. LBA2002)
  • 15 Nelson D F, Martz K L, Bonner H. et al . Non-Hodgkin’s lymphoma of the brain: can high dose, large volume radiation therapy improve survival? Report on a prospective trial by the Radiation Therapy Oncology Group (RTOG): RTOG 8315.  Int J Radiat Oncol Biol Phys. 1992;  23 9-17
  • 16 Shibamoto Y, Ogino H, Hasegawa M. et al . Results of radiation monotherapy for primary central nervous system lymphoma in the 1990s.  Int J Radiat Oncol Biol Phys. 2005;  62 809-813
  • 17 DeAngelis L M, Seiferheld W, Schold S C. et al . Radiation Therapy Oncology Group Study 93-10. Combination chemotherapy and radiotherapy for primary central nervous system lymphoma: Radiation Therapy Oncology Group Study 93–10.  J Clin Oncol. 2002;  20 4643-4648
  • 18 Poortmans P M, Kluin-Nelemans H C, Haaxma-Reiche H. et al . High-dose methotrexate-based chemotherapy followed by consolidating radiotherapy in non-AIDS-related primary central nervous system lymphoma: European Organization for Research and Treatment of Cancer Lymphoma Group Phase II Trial20962.  J Clin Oncol. 2003;  21 4483-4488
  • 19 Thiel E, Korfel A, Martus P. et al . High-dose methotrexate with or without whole brain radiotherapy for primary CNS lymphoma (G-PCNSL-SG-1): a phase 3, randomised, non-inferiority trial.  Lancet Oncol . 2010 Oct 20 [Epub ahead of print]; 
  • 20 Kocher M, Soffietti R, Abacioglu U. for the EORTC Radiation Oncology and Brain Tumor Groups . Adjuvant Whole Brain Radiotherapy versus Observation after Radiosurgery or Surgical Resection of 1–3 Cerebral Metastases – Results of the EORTC 22952-26001 Study.  J Clin Oncol akzeptiert.
  • 21 Griffin C A, Burger P, Morsberger L. et al . Identification of der(1;19)(q10;p10) in five oligodendrogliomas suggests mechanism of concurrent 1p and 19q loss.  J Neuropathol Exp Neurol. 2006;  65 988-994
  • 22 Jenkins R B, Blair H, Ballman K V. et al . A t(1;19)(q10;p10) mediates the combined deletions of 1p and 19q and predicts a better prognosis of patients with oligodendroglioma.  Cancer Res. 2006;  66 9852-9861
  • 23 Weller M, Berger H, Hartmann C. et al . for the German Glioma Network Combined 1p / 19q loss in oligodendroglial tumors: predictive or prognostic biomarker?.  Clin Cancer Res. 2007;  13 6933-6937
  • 24 Noushmehr H, Weisenberger D J, Diefes K. et al . Identification of a CpG island methylator phenotype that defines a distinct subgroup of glioma.  Cancer Cell. 2010;  17 510-522
  • 25 Hartmann C, Hentschel B, Wick W. et al . Patients with IDH1 wild type anaplastic astrocytomas exhibit worse prognosis than IDH1-mutated glioblastomas, and IDH1 mutation status accounts for the unfavorable prognostic effect of higher age: implications for classification of gliomas.  Acta Neuropathol. 2010;  120 707-718
  • 26 Stupp R, Mason W P, van den Bent M J. et al . on behalf of the European Organisation for Research and Treatment of Cancer (EORTC) Brain Tumor and Radiotherapy Groups and National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma.  N Engl J Med. 2005;  352 987-996
  • 27 Stupp R, Hegi M E, Mason W P. et al . Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial.  Lancet Oncol. 2009;  10 459-466
  • 28 Hegi M E, Diserens A-C, Gorlia T. et al . MGMT gene silencing and benefit from temozolomide in glioblastoma.  N Engl J Med. 2005;  352 997-1003
  • 29 Herrlinger U, Rieger J, Koch D. et al . UKT-03 phase II trial of CCNU plus temozolomide chemotherapy in addition to radiotherapy in newly diagnosed glioblastoma.  J Clin Oncol. 2006;  24 4412-4417
  • 30 Glas M, Happold C, Rieger J. et al . Long-term survival of glioblastoma patients treated with radiotherapy and lomustine plus temozolomide.  J Clin Oncol. 2009;  27 1257-61
  • 31 Weiler M, Hartmann C, Wiewrodt D. et al . Phase II trial of radiochemotherapy with daily concomitant and adjuvant intensified (one week on / one week off) temozolomide plus indomethacin in newly diagnosed glioblastoma: UKT-05.  Int J Rad Biol Phys. 2010;  77 670-676
  • 32 Illerhaus G, Marks R, Ihorst G. et al . High-dose chemotherapy with autologous stem-cell transplantation and hyperfractionated radiotherapy as first-line treatment of primary CNS lymphoma.  J Clin Oncol. 2006;  24 3865-3870
  • 33 Pels H, Schmidt-Wolf I G, Glasmacher A. et al . Primary central nervous system lymphoma: results of a pilot and phase II study of systemic and intraventricular chemotherapy with deferred radiotherapy.  J Clin Oncol. 2003;  21 4489-4495
  • 34 Jürgens A, Pels H, Rogowski S. et al . Long-term survival with favorable cognitive outcome after chemotherapy in primary central nervous system lymphoma.  Ann Neurol. 2010;  67 182-189

Prof. Dr. med. Wolfgang Wick

Abteilung Neuroonkologie, Neurologische Klinik & Nationales Zentrum für Tumorerkrankungen, Universitätsklinik Heidelberg

Im Neuenheimer Feld 400

69120 Heidelberg

Email: wolfgang.wick@med.uni-heidelberg.de

    >