Journal of Neuro-Oncology

, Volume 131, Issue 1, pp 125–133 | Cite as

Influence of glioblastoma contact with the lateral ventricle on survival: a meta-analysis

  • Akshitkumar M. Mistry
  • Andrew T. Hale
  • Lola B. Chambless
  • Kyle D. Weaver
  • Reid C. Thompson
  • Rebecca A. IhrieEmail author
Clinical Study


The ventricular-subventricular zone (V-SVZ), which lies in the walls of the lateral ventricles (LV), is the largest neurogenic niche within the adult brain. Whether radiographic contact with the LV influences survival in glioblastoma (GBM) patients remains unclear. We assimilated and analyzed published data comparing survival in GBM patients with (LV+GBM) and without (LV-GBM) radiographic LV contact. PubMed, EMBASE, and Cochrane electronic databases were searched. Fifteen studies with survival data on LV+GBM and LV-GBM patients were identified. Their Kaplan–Meier survival curves were digitized and pooled for generation of median overall (OS) and progression free (PFS) survivals and log-rank hazard ratios (HRs). The log-rank and reported multivariate HRs after accounting for the common predictors of GBM survival were analyzed separately by meta-analyses. The calculated median survivals (months) from pooled data were 12.95 and 16.58 (OS), and 4.54 and 6.25 (PFS) for LV+GBMs and LV-GBMs, respectively, with an overall log-rank HRs of 1.335 [1.204–1.513] (OS) and 1.387 [1.225–1.602] (PFS). Meta-analysis of log-rank HRs resulted in summary HRs of 1.58 [1.35–1.85] (OS, 10 studies) and 1.41 [1.22–1.64] (PFS, 5 studies). Meta-analysis of multivariate HRs resulted in summary HRs of 1.35 [1.14–1.58] (OS, 6 studies) and 1.64 [0.88–3.05] (PFS, 3 studies). Patients with GBM contacting the LV have lower survival. This effect may be independent of the common predictors of GBM survival, suggesting a clinical influence of V-SVZ contact on GBM biology.


Ventricular-subventricular zone V-SVZ Subventricular zone SVZ Glioblastoma Glioma Lateral ventricle 



We thank Dr. Tseng for providing unpublished Kaplan–Meier survival curves of LV+GBM and LV-GBM patient data analyzed in the study Liang et al. [22].


This work was by supported a grant from the Institute for Clinical and Translational Research, Vanderbilt University, part of the National Center for Advancing Translational Sciences, CTSA award No. UL1TR000445 (A.M.M.) and Discovery Grants from the Vanderbilt-Ingram Cancer Center (R.A.I.).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

11060_2016_2278_MOESM1_ESM.docx (476 kb)
Supplementary material 1 (DOCX 475 KB)


  1. 1.
    Gilbert MR, Dignam JJ, Armstrong TS, Wefel JS, Blumenthal DT, Vogelbaum MA, Colman H, Chakravarti A, Pugh S, Won M, Jeraj R, Brown PD, Jaeckle KA, Schiff D, Stieber VW, Brachman DG, Werner-Wasik M, Tremont-Lukats IW, Sulman EP, Aldape KD, Curran WJ Jr, Mehta MP (2014) A randomized trial of bevacizumab for newly diagnosed glioblastoma. N Engl J Med 370:699–708. doi: 10.1056/NEJMoa1308573 CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Chinot OL, Wick W, Mason W, Henriksson R, Saran F, Nishikawa R, Carpentier AF, Hoang-Xuan K, Kavan P, Cernea D, Brandes AA, Hilton M, Abrey L, Cloughesy T (2014) Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma. N Engl J Med 370:709–722. doi: 10.1056/NEJMoa1308345 CrossRefPubMedGoogle Scholar
  3. 3.
    Bao S, Wu Q, McLendon RE, Hao Y, Shi Q, Hjelmeland AB, Dewhirst MW, Bigner DD, Rich JN (2006) Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature 444:756–760. doi: 10.1038/nature05236 CrossRefPubMedGoogle Scholar
  4. 4.
    Chen J, Li Y, Yu TS, McKay RM, Burns DK, Kernie SG, Parada LF (2012) A restricted cell population propagates glioblastoma growth after chemotherapy. Nature 488:522–526. doi: 10.1038/nature11287 CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Sanai N, Tramontin AD, Quinones-Hinojosa A, Barbaro NM, Gupta N, Kunwar S, Lawton MT, McDermott MW, Parsa AT, Manuel-Garcia Verdugo J, Berger MS, Alvarez-Buylla A (2004) Unique astrocyte ribbon in adult human brain contains neural stem cells but lacks chain migration. Nature 427:740–744. doi: 10.1038/nature02301 CrossRefPubMedGoogle Scholar
  6. 6.
    Sanai N, Nguyen T, Ihrie RA, Mirzadeh Z, Tsai HH, Wong M, Gupta N, Berger MS, Huang E, Garcia-Verdugo JM, Rowitch DH, Alvarez-Buylla A (2011) Corridors of migrating neurons in the human brain and their decline during infancy. Nature 478:382–386. doi: 10.1038/nature10487 CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Curtis MA, Kam M, Nannmark U, Anderson MF, Axell MZ, Wikkelso C, Holtas S, van Roon-Mom WM, Bjork-Eriksson T, Nordborg C, Frisen J, Dragunow M, Faull RL, Eriksson PS (2007) Human neuroblasts migrate to the olfactory bulb via a lateral ventricular extension. Science 315:1243–1249. doi: 10.1126/science.1136281 CrossRefPubMedGoogle Scholar
  8. 8.
    Ernst A, Alkass K, Bernard S, Salehpour M, Perl S, Tisdale J, Possnert G, Druid H, Frisen J (2014) Neurogenesis in the striatum of the adult human brain. Cell 156:1072–1083. doi: 10.1016/j.cell.2014.01.044 CrossRefPubMedGoogle Scholar
  9. 9.
    Lim DA, Cha S, Mayo MC, Chen MH, Keles E, VandenBerg S, Berger MS (2007) Relationship of glioblastoma multiforme to neural stem cell regions predicts invasive and multifocal tumor phenotype. Neuro-oncol 9:424–429. doi: 10.1215/15228517-2007-023 CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Moher D, Liberati A, Tetzlaff J, Altman DG, Group P (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Medicine 6:e1000097. doi: 10.1371/journal.pmed.1000097 CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Chaichana KL, McGirt MJ, Frazier J, Attenello F, Guerrero-Cazares H, Quinones-Hinojosa A (2008) Relationship of glioblastoma multiforme to the lateral ventricles predicts survival following tumor resection. J Neurooncol 89:219–224. doi: 10.1007/s11060-008-9609-2 CrossRefPubMedGoogle Scholar
  12. 12.
    Chaichana K, Parker S, Olivi A, Quinones-Hinojosa A (2010) A proposed classification system that projects outcomes based on preoperative variables for adult patients with glioblastoma multiforme. J Neurosurg 112:997–1004. doi: 10.3171/2009.9.JNS09805 CrossRefPubMedGoogle Scholar
  13. 13.
    Kappadakunnel M, Eskin A, Dong J, Nelson SF, Mischel PS, Liau LM, Ngheimphu P, Lai A, Cloughesy TF, Goldin J, Pope WB (2010) Stem cell associated gene expression in glioblastoma multiforme: relationship to survival and the subventricular zone. J Neurooncol 96:359–367. doi: 10.1007/s11060-009-9983-4 CrossRefPubMedGoogle Scholar
  14. 14.
    Young GS, Macklin EA, Setayesh K, Lawson JD, Wen PY, Norden AD, Drappatz J, Kesari S (2011) Longitudinal MRI evidence for decreased survival among periventricular glioblastoma. J Neurooncol 104:261–269. doi: 10.1007/s11060-010-0477-1 CrossRefPubMedGoogle Scholar
  15. 15.
    Tejada-Solis S, Aldave-Orzaiz G, Pay-Valverde E, Marigil-Sanchez M, Idoate-Gastearena MA, Diez-Valle R (2012) Prognostic value of ventricular wall fluorescence during 5-aminolevulinic-guided surgery for glioblastoma. Acta neurochirurgica 154: 1997–2002. doi: 10.1007/s00701-012-1475-1 (discussion 2002)CrossRefPubMedGoogle Scholar
  16. 16.
    Chaichana KL, Pendleton C, Chambless L, Camara-Quintana J, Nathan JK, Hassam-Malani L, Li G, Harsh GRt, Thompson RC, Lim M, Quinones-Hinojosa A (2013) Multi-institutional validation of a preoperative scoring system which predicts survival for patients with glioblastoma. J Clin Neurosci 20:1422–1426. doi: 10.1016/j.jocn.2013.02.007 CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Ho J, Ondos J, Ning H, Smith S, Kreisl T, Iwamoto F, Sul J, Kim L, McNeil K, Krauze A, Shankavaram U, Fine HA, Camphausen K (2013) Chemoirradiation for glioblastoma multiforme: the national cancer institute experience. PloS One 8:e70745. doi: 10.1371/journal.pone.0070745 CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Jafri NF, Clarke JL, Weinberg V, Barani IJ, Cha S (2013) Relationship of glioblastoma multiforme to the subventricular zone is associated with survival. Neuro-oncol 15:91–96. doi: 10.1093/neuonc/nos268 CrossRefPubMedGoogle Scholar
  19. 19.
    Adeberg S, Konig L, Bostel T, Harrabi S, Welzel T, Debus J, Combs SE (2014) Glioblastoma recurrence patterns after radiation therapy with regard to the subventricular zone. Int J Radiat Oncol Biol Phys 90:886–893. doi: 10.1016/j.ijrobp.2014.07.027 CrossRefPubMedGoogle Scholar
  20. 20.
    Sonoda Y, Saito R, Kanamori M, Kumabe T, Uenohara H, Tominaga T (2014) The association of subventricular zone involvement at recurrence with survival after repeat surgery in patients with recurrent glioblastoma. Neurologia Medico-Chirurgica 54: 302–309CrossRefPubMedGoogle Scholar
  21. 21.
    Tomita T, Akimoto J, Haraoka J, Kudo M (2014) Clinicopathological significance of expression of nestin, a neural stem/progenitor cell marker, in human glioma tissue. Brain Tumor Pathol 31:162–171. doi: 10.1007/s10014-013-0169-6 CrossRefPubMedGoogle Scholar
  22. 22.
    Han S, Li X, Qiu B, Jiang T, Wu A (2015) Can lateral ventricle contact predict the ontogeny and prognosis of glioblastoma? J Neurooncol 124:45–55. doi: 10.1007/s11060-015-1818-x CrossRefPubMedGoogle Scholar
  23. 23.
    Liang TH, Kuo SH, Wang CW, Chen WY, Hsu CY, Lai SF, Tseng HM, You SL, Chen CM, Tseng WI (2015) Adverse prognosis and distinct progression patterns after concurrent chemoradiotherapy for glioblastoma with synchronous subventricular zone and corpus callosum invasion. Radiother Oncol: J Eur Soc Ther Radiol Int Soc Cell. doi: 10.1016/j.radonc.2015.11.017 Google Scholar
  24. 24.
    Nestler U, Lutz K, Pichlmeier U, Stummer W, Franz K, Reulen HJ, Bink A, Group ALAGS (2015) Anatomic features of glioblastoma and their potential impact on survival. Acta neurochirurgica 157: 179–186. doi: 10.1007/s00701-014-2271-x CrossRefPubMedGoogle Scholar
  25. 25.
    Pina Batista KM, Vega IF, de Eulate-Beramendi SA, Morales J, Kurbanov A, Asnel D, Meilan A, Astudillo A (2015) Prognostic significance of the markers IDH1 and YKL40 related to the subventricular zone. Folia Neuropathol 53:52–59CrossRefPubMedGoogle Scholar
  26. 26.
    Wan X, Peng L, Li Y (2015) A review and comparison of methods for recreating individual patient data from published Kaplan–Meier survival curves for economic evaluations: a simulation study. PloS One 10:e0121353. doi: 10.1371/journal.pone.0121353 CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Guyot P, Ades AE, Ouwens MJ, Welton NJ (2012) Enhanced secondary analysis of survival data: reconstructing the data from published Kaplan–Meier survival curves. BMC Med Res Methodol 12:9. doi: 10.1186/1471-2288-12-9 CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Higgins J, Green S (2011) Cochrane handbook for systematic reviews of interventions. The Cochrane Collaboration. Wiley-Blackwell: ChichesterGoogle Scholar
  29. 29.
    Machin D, Cheung YB, Parmar M (2006) Survival analysis: A practical approach. WileyGoogle Scholar
  30. 30.
    Galvao RP, Kasina A, McNeill RS, Harbin JE, Foreman O, Verhaak RG, Nishiyama A, Miller CR, Zong H (2014) Transformation of quiescent adult oligodendrocyte precursor cells into malignant glioma through a multistep reactivation process. Proc Natl Acad Sci USA 111:E4214–E4223. doi: 10.1073/pnas.1414389111 CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Alcantara Llaguno SR, Wang Z, Sun D, Chen J, Xu J, Kim E, Hatanpaa KJ, Raisanen JM, Burns DK, Johnson JE, Parada LF (2015) Adult lineage-restricted CNS progenitors specify distinct glioblastoma subtypes. Cancer Cell 28:429–440. doi: 10.1016/j.ccell.2015.09.007 CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Liu C, Sage JC, Miller MR, Verhaak RG, Hippenmeyer S, Vogel H, Foreman O, Bronson RT, Nishiyama A, Luo L, Zong H (2011) Mosaic analysis with double markers reveals tumor cell of origin in glioma. Cell 146:209–221. doi: 10.1016/j.cell.2011.06.014 CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Zong H, Parada LF, Baker SJ (2015) Cell of origin for malignant gliomas and its implication in therapeutic development. Cold Spring Harbor Perspectives Biol 7. doi: 10.1101/cshperspect.a020610
  34. 34.
    Kusne Y, Sanai N (2015) The SVZ and its relationship to stem cell based neuro-oncogenesis. Adv Exp Med Biol 853:23–32. doi: 10.1007/978-3-319-16537-0_2 CrossRefPubMedGoogle Scholar
  35. 35.
    Marumoto T, Tashiro A, Friedmann-Morvinski D, Scadeng M, Soda Y, Gage FH, Verma IM (2009) Development of a novel mouse glioma model using lentiviral vectors. Nat Med 15:110–116. doi: 10.1038/nm.1863 CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Friedmann-Morvinski D, Bushong EA, Ke E, Soda Y, Marumoto T, Singer O, Ellisman MH, Verma IM (2012) Dedifferentiation of neurons and astrocytes by oncogenes can induce gliomas in mice. Science 338:1080–1084. doi: 10.1126/science.1226929 CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Bohman LE, Swanson KR, Moore JL, Rockne R, Mandigo C, Hankinson T, Assanah M, Canoll P, Bruce JN (2010) Magnetic resonance imaging characteristics of glioblastoma multiforme: implications for understanding glioma ontogeny. Neurosurgery 67:1319–1327. doi: 10.1227/NEU.0b013e3181f556ab (discussion 1327–1318)CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Haskins WE, Zablotsky BL, Foret MR, Ihrie RA, Alvarez-Buylla A, Eisenman RN, Berger MS, Lin CH (2013) Molecular Characteristics in MRI-Classified Group 1 Glioblastoma Multiforme. Front Oncol 3:182. doi: 10.3389/fonc.2013.00182 CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Kroonen J, Nassen J, Boulanger YG, Provenzano F, Capraro V, Bours V, Martin D, Deprez M, Robe P, Rogister B (2011) Human glioblastoma-initiating cells invade specifically the subventricular zones and olfactory bulbs of mice after striatal injection. Int J Cancer 129:574–585. doi: 10.1002/ijc.25709 CrossRefPubMedGoogle Scholar
  40. 40.
    Sadahiro H, Yoshikawa K, Ideguchi M, Kajiwara K, Ishii A, Ikeda E, Owada Y, Yasumoto Y, Suzuki M (2014) Pathological features of highly invasive glioma stem cells in a mouse xenograft model. Brain Tumor Pathol 31:77–84. doi: 10.1007/s10014-013-0149-x CrossRefPubMedGoogle Scholar
  41. 41.
    Goffart N, Kroonen J, Di Valentin E, Dedobbeleer M, Denne A, Martinive P, Rogister B (2015) Adult mouse subventricular zones stimulate glioblastoma stem cells specific invasion through CXCL12/CXCR4 signaling. Neuro-Oncol 17:81–94. doi: 10.1093/neuonc/nou144 CrossRefPubMedGoogle Scholar
  42. 42.
    Aboody KS, Brown A, Rainov NG, Bower KA, Liu S, Yang W, Small JE, Herrlinger U, Ourednik V, Black PM, Breakefield XO, Snyder EY (2000) Neural stem cells display extensive tropism for pathology in adult brain: evidence from intracranial gliomas. Proc Natl Acad Sci USA 97:12846–12851. doi: 10.1073/pnas.97.23.12846 CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Ziu M, Schmidt NO, Cargioli TG, Aboody KS, Black PM, Carroll RS (2006) Glioma-produced extracellular matrix influences brain tumor tropism of human neural stem cells. J Neurooncol 79:125–133. doi: 10.1007/s11060-006-9121-5 CrossRefPubMedGoogle Scholar
  44. 44.
    Zhao D, Najbauer J, Garcia E, Metz MZ, Gutova M, Glackin CA, Kim SU, Aboody KS (2008) Neural stem cell tropism to glioma: critical role of tumor hypoxia. Mol Cancer Res: MCR 6:1819–1829. doi: 10.1158/1541-7786.mcr-08-0146 CrossRefPubMedGoogle Scholar
  45. 45.
    Capilla-Gonzalez V, Lavell E, Quinones-Hinojosa A, Guerrero-Cazares H (2015) Regulation of subventricular zone-derived cells migration in the adult brain. Adv Exp Med Biol 853:1–21. doi: 10.1007/978-3-319-16537-0_1 CrossRefPubMedGoogle Scholar
  46. 46.
    Berendsen S, Schoysman L, Kroonen J, Hendrikse J, Seute T, Spliet WGM, Poulet C, Bours V, Robe PA (2015) Glioblastoma involving the subventricular zone: correlations to patient survival and tumor biology. Abstracts from the 20th Annual Scientific Meeting of the Society for Neuro-Oncology. Oxford University Press, San Antonio, p v79Google Scholar
  47. 47.
    Fahrendorf D, Hesselmann V, Schwindt W, Wolfer J, Jeibmann A, Kooijman H, Kugel H, Heindel W, Bink A (2015) Variations of ITSS-morphology and their relationship to location and tumor volume in patients with Glioblastoma. J Neuroimaging. doi: 10.1111/jon.12228 PubMedGoogle Scholar
  48. 48.
    Chen L, Guerrero-Cazares H, Ye X, Ford E, McNutt T, Kleinberg L, Lim M, Chaichana K, Quinones-Hinojosa A, Redmond K (2013) Increased subventricular zone radiation dose correlates with survival in glioblastoma patients after gross total resection. Int J Radiat Oncol Biol Phys 86:616–622. doi: 10.1016/j.ijrobp.2013.02.014 CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Lee P, Eppinga W, Lagerwaard F, Cloughesy T, Slotman B, Nghiemphu PL, Wang PC, Kupelian P, Agazaryan N, Demarco J, Selch MT, Steinberg M, Kang JJ (2013) Evaluation of high ipsilateral subventricular zone radiation therapy dose in glioblastoma: a pooled analysis. Int J Radiat Oncol Biol Phys 86:609–615. doi: 10.1016/j.ijrobp.2013.01.009 CrossRefPubMedGoogle Scholar
  50. 50.
    Elicin O, Inac E, Uzel EK, Karacam S, Uzel OE (2014) Relationship between survival and increased radiation dose to subventricular zone in glioblastoma is controversial. J Neurooncol 118:413–419. doi: 10.1007/s11060-014-1424-3 CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Akshitkumar M. Mistry
    • 1
  • Andrew T. Hale
    • 3
  • Lola B. Chambless
    • 1
  • Kyle D. Weaver
    • 1
  • Reid C. Thompson
    • 1
  • Rebecca A. Ihrie
    • 1
    • 2
    Email author
  1. 1.Department of NeurosurgeryVanderbilt University Medical CenterNashvilleUSA
  2. 2.Department of Cancer BiologyVanderbilt UniversityNashvilleUSA
  3. 3.Medical Scientist Training ProgramVanderbilt University Medical CenterNashvilleUSA

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