Journal of Neuro-Oncology

, Volume 120, Issue 3, pp 451–457 | Cite as

An individual patient data meta-analysis on characteristics, treatments and outcomes of the glioblastoma/gliosarcoma patients with central nervous system metastases reported in literature until 2013

  • Sophie Pietschmann
  • André O. von Bueren
  • Guido Henke
  • Michael Josef Kerber
  • Rolf-Dieter Kortmann
  • Klaus Müller
Topic Review


Dissemination of high-grade gliomas (WHO IV) has been investigated poorly so far. We conducted an extensive analysis of the characteristics, treatments and outcomes of the glioblastoma multiforme (GBM)/gliosarcoma (GS) patients with central nervous system (CNS) metastases reported in literature until April 2013. PubMed and Web of Science searches for peer-reviewed articles pertaining to GBM/GS patients with metastatic disease were conducted using predefined keywords. Additionally, we performed hand search following the references from the selected papers. Cases in which the metastases exclusively occurred outside the CNS were excluded. 110 publications reporting on 189 patients were eligible. There was a significant increase in the number of reported cases over the last decades. We calculated a median overall survival from diagnosis of metastasis (from initial diagnosis of GBM/GS) of 3.0 ± 0.3 (11 ± 0.7) months. On univariate analyses, gender, age, the histological subtype, the time interval between initial diagnosis and the occurrence of metastases and the location of CNS metastasis (intracranial versus spinal and parenchymal versus leptomeningeal, respectively) did not influence survival after diagnosis of metastasis. There was no substantial treatment progress over the recent decades. GBM/GS with CNS metastasis are associated with a dismal prognosis. Crucial treatment progress is not evident. A central registry should be considered to consecutively gain more information about the ideal therapeutic approach.


Glioblastoma Gliosarcoma CNS Metastasis Metastatic Individual patient data meta-analysis 



We are indebted to the authors of articles, who provided the data to this study that otherwise would have not been possible. We would like to thank Mrs. Christiane Hofmann for assisting the literature search.

Conflict of interest

The author(s) indicated no potential conflicts of interest.

Ethical standards

This manuscript is in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its subsequent amendments.

Supplementary material

11060_2014_1596_MOESM1_ESM.pdf (487 kb)
Supplementary material 1 (PDF 486 kb)
11060_2014_1596_MOESM2_ESM.docx (31 kb)
Supplementary material 2 (DOCX 30 kb)


  1. 1.
    Gebhardt BJ, Dobelbower MC, Ennis WH, Bag AK, Markert JM, Fiveash JB (2014) Patterns of failure for glioblastoma multiforme following limited-margin radiation and concurrent temozolomide. Radiat Oncol 9:130. doi: 10.1186/1748-717X-9-130 PubMedCentralPubMedCrossRefGoogle Scholar
  2. 2.
    Vertosick FT Jr, Selker RG (1990) Brain stem and spinal metastases of supratentorial glioblastoma multiforme: a clinical series. Neurosurgery 27 (4):516–521; discussion 521–512Google Scholar
  3. 3.
    Tendulkar RD, Pai Panandiker AS, Wu S, Kun LE, Broniscer A, Sanford RA, Merchant TE (2010) Irradiation of pediatric high-grade spinal cord tumors. Int J Radiat Oncol Biol Phys 78(5):1451–1456. doi: 10.1016/j.ijrobp.2009.09.071 PubMedCrossRefGoogle Scholar
  4. 4.
    Müller K, Schlamann A, Guckenberger M, Warmuth-Metz M, Gluck A, Pietschmann S, Wawer A, Kortmann RD, Kramm C, von Bueren AO (2014) Craniospinal irradiation with concurrent temozolomide for primary metastatic pediatric high-grade or diffuse intrinsic pontine gliomas. A first report from the GPOH-HIT-HGG Study Group. Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft [et al] 190 (4):377–381. doi: 10.1007/s00066-013-0513-0
  5. 5.
    Moher D, Liberati A, Tetzlaff J, Altman DG, Group P (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. J Clin Epidemiol 62(10):1006–1012. doi: 10.1016/j.jclinepi.2009.06.005 CrossRefGoogle Scholar
  6. 6.
    Chang CH, Housepian EM, Herbert C Jr (1969) An operative staging system and a megavoltage radiotherapeutic technic for cerebellar medulloblastomas. Radiology 93(6):1351–1359PubMedCrossRefGoogle Scholar
  7. 7.
    Stupp R, Mason WP, van Den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO, European Organisation for R, Treatment of Cancer Brain T, Radiotherapy G, National Cancer Institute of Canada Clinical Trials G (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. New Engl J Med 352(10):987–996. doi: 10.1056/NEJMoa043330 PubMedCrossRefGoogle Scholar
  8. 8.
    Kalokhe G, Grimm SA, Chandler JP, Helenowski I, Rademaker A, Raizer JJ (2012) Metastatic glioblastoma: case presentations and a review of the literature. J Neuro Oncol 107(1):21–27. doi: 10.1007/s11060-011-0731-1 CrossRefGoogle Scholar
  9. 9.
    Shahideh M, Fallah A, Munoz DG, Loch Macdonald R (2012) Systematic review of primary intracranial glioblastoma multiforme with symptomatic spinal metastases, with two illustrative patients. J Clin Neurosci 19(8):1080–1086. doi: 10.1016/j.jocn.2011.09.024 PubMedCrossRefGoogle Scholar
  10. 10.
    Lawton CD, Nagasawa DT, Yang I, Fessler RG, Smith ZA (2012) Leptomeningeal spinal metastases from glioblastoma multiforme: treatment and management of an uncommon manifestation of disease. J Neurosurg Spine 17(5):438–448. doi: 10.3171/2012.7.SPINE12212 PubMedCrossRefGoogle Scholar
  11. 11.
    Maslehaty H, Cordovi S, Hefti M (2011) Symptomatic spinal metastases of intracranial glioblastoma: clinical characteristics and pathomechanism relating to GFAP expression. J Neuro Oncol 101(2):329–333. doi: 10.1007/s11060-010-0257-y CrossRefGoogle Scholar
  12. 12.
    Lindsay A, Holthouse D, Robbins P, Knuckey N (2002) Spinal leptomeningeal metastases following glioblastoma multiforme treated with radiotherapy. J Clin Neurosci 9(6):725–728PubMedCrossRefGoogle Scholar
  13. 13.
    MacDonald TJ, Aguilera D, Kramm CM (2011) Treatment of high-grade glioma in children and adolescents. Neuro Oncol 13(10):1049–1058. doi: 10.1093/neuonc/nor092 PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Galanis E, Buckner JC, Dinapoli RP, Scheithauer BW, Jenkins RB, Wang CH, O’Fallon JR, Farr G Jr (1998) Clinical outcome of gliosarcoma compared with glioblastoma multiforme: North Central Cancer Treatment Group results. J Neurosurg 89(3):425–430. doi: 10.3171/jns.1998.89.3.0425 PubMedCrossRefGoogle Scholar
  15. 15.
    Jenkin D, Shabanah MA, Shail EA, Gray A, Hassounah M, Khafaga Y, Kofide A, Mustafa M, Schultz H (2000) Prognostic factors for medulloblastoma. Int J Radiat Oncol Biol Phys 47(3):573–584PubMedCrossRefGoogle Scholar
  16. 16.
    Zwiener I, Blettner M, Hommel G (2011) Survival analysis: part 15 of a series on evaluation of scientific publications. Deutsches Arzteblatt Int 108(10):163–169. doi: 10.3238/arztebl.2010.0163 Google Scholar
  17. 17.
    Brat DJ, Ryken TC, Kalkanis SN, Olson JJ, Committee ACJG (2014) The role of neuropathology in the management of progressive glioblastoma : a systematic review and evidence-based clinical practice guideline. J Neuro Oncol 118(3):461–478. doi: 10.1007/s11060-013-1331-z CrossRefGoogle Scholar
  18. 18.
    Olson JJ, Nayak L, Ormond DR, Wen PY, Kalkanis SN, Committee ACJG (2014) The role of cytotoxic chemotherapy in the management of progressive glioblastoma : a systematic review and evidence-based clinical practice guideline. J Neuro Oncol 118(3):501–555. doi: 10.1007/s11060-013-1338-5 CrossRefGoogle Scholar
  19. 19.
    Olson JJ, Nayak L, Ormond DR, Wen PY, Kalkanis SN, Ryken TC, Committee ACJG (2014) The role of targeted therapies in the management of progressive glioblastoma : a systematic review and evidence-based clinical practice guideline. J Neuro Oncol 118(3):557–599. doi: 10.1007/s11060-013-1339-4 CrossRefGoogle Scholar
  20. 20.
    Ryken TC, Aygun N, Morris J, Schweizer M, Nair R, Spracklen C, Kalkanis SN, Olson JJ, Committee ACJG (2014) The role of imaging in the management of progressive glioblastoma : a systematic review and evidence-based clinical practice guideline. J Neuro Oncol 118(3):435–460. doi: 10.1007/s11060-013-1330-0 CrossRefGoogle Scholar
  21. 21.
    Ryken TC, Kalkanis SN, Buatti JM, Olson JJ, Committee ACJG (2014) The role of cytoreductive surgery in the management of progressive glioblastoma : a systematic review and evidence-based clinical practice guideline. J Neuro Oncol 118(3):479–488. doi: 10.1007/s11060-013-1336-7 CrossRefGoogle Scholar
  22. 22.
    Ryu S, Buatti JM, Morris A, Kalkanis SN, Ryken TC, Olson JJ, Committee ACJG (2014) The role of radiotherapy in the management of progressive glioblastoma : a systematic review and evidence-based clinical practice guideline. J Neuro Oncol 118(3):489–499. doi: 10.1007/s11060-013-1337-6 CrossRefGoogle Scholar
  23. 23.
    Blettner M, Schlehofer B, Sauerbrei W (1997) Limitations of meta-analysis from published data in epidemiological research. Soz Praventivmed 42(2):95–104PubMedCrossRefGoogle Scholar
  24. 24.
    Mazloom A, Hodges JC, Teh BS, Chintagumpala M, Paulino AC (2012) Outcome of patients with pilocytic astrocytoma and leptomeningeal dissemination. Int J Radiat Oncol Biol Phys 84(2):350–354. doi: 10.1016/j.ijrobp.2011.12.044 PubMedCrossRefGoogle Scholar
  25. 25.
    Müller K, Diez B, Muggeri A, Pietsch T, Friedrich C, Rutkowski S, von Hoff K, von Bueren AO, Zwiener I, Bruns F (2013) What’s in a name? Intracranial peripheral primitive neuroectodermal tumors and CNS primitive neuroectodermal tumors are not the same. Strahlenther Onkol 189(5):372–379. doi: 10.1007/s00066-013-0315-4 PubMedCrossRefGoogle Scholar
  26. 26.
    Moergel M, Meurer P, Ingel K, Wendt TG, Al-Nawas B (2011) Effectiveness of postoperative radiotherapy in patients with small oral and oropharyngeal squamous cell carcinoma and concomitant ipsilateral singular cervical lymph node metastasis (pN1): a meta-analysis. Strahlenther Onkol 187(6):337–343. doi: 10.1007/s00066-011-2206-x PubMedCrossRefGoogle Scholar
  27. 27.
    Erpolat OP, Gocun PU, Akmansu M, Ozgun G, Akyol G (2013) Hypoxia-related molecules HIF-1alpha, CA9, and osteopontin : predictors of survival in patients with high-grade glioma. Strahlenther Onkol 189(2):147–154. doi: 10.1007/s00066-012-0262-5 PubMedCrossRefGoogle Scholar
  28. 28.
    Murphy M, Parney IF (2014) Clinical trials in neurosurgical oncology. J Neuro Oncol. doi: 10.1007/s11060-014-1569-0 Google Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Sophie Pietschmann
    • 1
  • André O. von Bueren
    • 2
  • Guido Henke
    • 3
  • Michael Josef Kerber
    • 1
  • Rolf-Dieter Kortmann
    • 1
  • Klaus Müller
    • 1
    • 4
  1. 1.Department for Radiation OncologyUniversity of Leipzig Medical CenterLeipzigGermany
  2. 2.Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent MedicineUniversity Medical Center GoettingenGoettingenGermany
  3. 3.Department of Radiation OncologyKantonsspital St. GallenSt. GallenSwitzerland
  4. 4.Strahlentherapie Uniklinik LeipzigLeipzigGermany

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