Skip to main content
SpringerLink
Log in

Influence of glioblastoma contact with the subventricular zone on survival and recurrence patterns

  • Research Article
  • Published:
Clinical and Translational Oncology Aims and scope Submit manuscript

Abstract

Background

There is growing evidence that the subventricular zone (SVZ) may be involved in both the initiation and progression of glioblastoma (GB). We aimed to assess tumor proximity to the SVZ as a potential prognostic factor in GB.

Method

Retrospective study of 133 patients diagnosed with primary GB who underwent surgery followed by temozolomide-based chemoradiation between 2010 and 2016. All lesions were classified according to their anatomic relation with the SVZ. We determined the effect of tumor contact with the SVZ on progression-free survival (PFS), overall survival (OS), type, and patterns of recurrence.

Results

At a median follow-up of 18.6 months (95% CI 15.9–21.2), PFS and OS were 7.5 (95% CI 6.7–8.3) and 13.9 (95% CI 10.9–16.9) months, respectively. On the univariate analyses, initial contact with the SVZ was a factor for poor prognosis for both PFS (6.1 vs. 8.7 months; p = 0.006) and OS (10.6 vs. 17.9 months; p = 0.037). On the multivariate analysis, tumor contact with the SVZ remained statistically significant for PFS, but not OS. Patients with SVZ-contacting tumors presented a higher rate of aggressive clinical progression (30.9% vs. 11.3%; p = 0.007) and contralateral relapse patterns (23.4% vs. 9.1%; p = 0.048).

Conclusions

Our results suggest that glioblastoma contact with the SVZ appears to be an independent prognostic factor for poor PFS. The presence of an SVZ-contacting tumor was associated with more aggressive recurrences and a higher rate of contralateral relapses. These findings suggest that this variable may be a new prognostic factor in glioblastoma.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Ostrom QT, Gittleman H, Xu J, Kromer C, Wolinsky Y, Kruchko C, et al. CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2009–2013. Neuro-Oncology. 2016;18(suppl_5):v1–v75.

    Article  Google Scholar 

  2. Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature. 2001;414(6859):105–11.

    Article  CAS  Google Scholar 

  3. Alcantara Llaguno SR, Parada LF. Cell of origin of glioma: biological and clinical implications. Br J Cancer. 2016;115(12):1445–500.

    Article  Google Scholar 

  4. Liu C, Sage JC, Miller MR, Verhaak RGW, Hippenmeyer S, Vogel H, et al. Mosaic analysis with double markers reveals tumor cell of origin in glioma. Cell. 2011;146(2):209–21.

    Article  CAS  Google Scholar 

  5. Sanai N, Tramontin AD, Quiñones-Hinojosa A, Barbaro NM, Gupta N, Kunwar S, et al. Unique astrocyte ribbon in adult human brain contains neural stem cells but lacks chain migration. Nature. 2004;427(6976):740–4.

    Article  CAS  Google Scholar 

  6. Doetsch F, Garcıa-Verdugo JM, Alvarez-Buylla A. Cellular composition and three-dimensional organization of the subventricular germinal zone in the adult mammalian brain. J Neurosci. 1997;17(13):5046–5061. https://doi.org/10.1523/JNEUROSCI.17-13-05046.1997.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Dulken BW, Leeman DS, Boutet SC, Hebestreit K, Brunet A. Single-cell transcriptomic analysis defines heterogeneity and transcriptional dynamics in the adult neural stem cell lineage. Cell Rep. 2017;18(3):777–90.

    Article  CAS  Google Scholar 

  8. Lantos PL. The role of the subependymal plate in the origin of gliomas induced by ethylnitrosourea in the rat brain. Experientia. 1977;33(4):521–2.

    Article  CAS  Google Scholar 

  9. Vick NA, Lin MJ, Bigner DD. The role of the subependymal plate in glial tumorigenesis. Acta Neuropathol (Berl). 1977;40(1):63–71.

    Article  CAS  Google Scholar 

  10. Zhu Y, Guignard F, Zhao D, Liu L, Burns DK, Mason RP, et al. Early inactivation of p53 tumor suppressor gene cooperating with NF1 loss induces malignant astrocytoma. Cancer Cell. 2005;8(2):119–30.

    Article  CAS  Google Scholar 

  11. Alcantara Llaguno S, Chen J, Kwon C-H, Jackson EL, Li Y, Burns DK, et al. Malignant astrocytomas originate from neural stem/progenitor cells in a somatic tumor suppressor mouse model. Cancer Cell. 2009;15(1):45–56.

    Article  Google Scholar 

  12. Piccirillo SG, Spiteri I, Sottoriva A, Touloumis A, Ber S, Price SJ, et al. Contributions to drug resistance in glioblastoma derived from malignant cells in the sub-ependymal zone. Cancer Res. 2015;75(1):194–202.

    Article  CAS  Google Scholar 

  13. Chaichana KL, McGirt MJ, Frazier J, Attenello F, Guerrero-Cazares H, Quinones-Hinojosa A. Relationship of glioblastoma multiforme to the lateral ventricles predicts survival following tumor resection. J Neurooncol. 2008;89(2):219–24.

    Article  Google Scholar 

  14. Jafri NF, Clarke JL, Weinberg V, Barani IJ, Cha S. Relationship of glioblastoma multiforme to the subventricular zone is associated with survival. Neuro-Oncology. 2013;15(1):91–6.

    Article  CAS  Google Scholar 

  15. Lim DA, Cha S, Mayo MC, Chen M-H, Keles E, VandenBerg S, et al. Relationship of glioblastoma multiforme to neural stem cell regions predicts invasive and multifocal tumor phenotype. Neuro-Oncology. 2007;9(4):424–9.

    Article  Google Scholar 

  16. Young GS, Macklin EA, Setayesh K, Lawson JD, Wen PY, Norden AD, et al. Longitudinal MRI evidence for decreased survival among periventricular glioblastoma. J Neurooncol. 2011;104(1):261–9.

    Article  Google Scholar 

  17. Adeberg S, König L, Bostel T, Harrabi S, Welzel T, Debus J, et al. Glioblastoma recurrence patterns after radiation therapy with regard to the subventricular zone. Int J Radiat Oncol. 2014;90(4):886–93.

    Article  Google Scholar 

  18. Chen L, Chaichana KL, Kleinberg L, Ye X, Quinones-Hinojosa A, Redmond K. Glioblastoma recurrence patterns near neural stem cell regions. Radiother Oncol. 2015;116(2):294–300.

    Article  Google Scholar 

  19. Adeberg S, Bostel T, König L, Welzel T, Debus J, Combs SE. A comparison of long-term survivors and short-term survivors with glioblastoma, subventricular zone involvement: a predictive factor for survival? Radiat Oncol. 2014;9(1):95.

    Article  Google Scholar 

  20. Khalifa J, Tensaouti F, Lusque A, Plas B, Lotterie J-A, Benouaich-Amiel A, et al. Subventricular zones: new key targets for glioblastoma treatment. Radiat Oncol [Internet]. 2017. https://doi.org/10.1186/s13014-017-0791-2(cited 2017 Sep 15).

    Article  PubMed  PubMed Central  Google Scholar 

  21. Barani IJ, Cuttino LW, Benedict SH, Todor D, Bump EA, Wu Y, et al. Neural stem cell-preserving external-beam radiotherapy of central nervous system malignancies. Int J Radiat Oncol. 2007;68(4):978–85.

    Article  Google Scholar 

  22. Stupp R, Mason WP, Van Den Bent MJ, Weller M, Fisher B, Taphoorn MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352(10):987–96.

    Article  CAS  Google Scholar 

  23. Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJ, Janzer RC, 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(5):459–66.

    Article  CAS  Google Scholar 

  24. Roa W, Brasher PMA, Bauman G, Anthes M, Bruera E, Chan A, et al. Abbreviated course of radiation therapy in older patients with glioblastoma multiforme: a prospective randomized clinical trial. J Clin Oncol. 2004;22(9):1583–8.

    Article  CAS  Google Scholar 

  25. Kusumawidjaja G, Gan PZ, Ong WS, Teyateeti A, Dankulchai P, Tan YD, Chua ET, Chua KL, Tham CK, Wong FY, Chua M. Dose-escalated intensity-modulated radiotherapy and irradiation of subventricular zones in relation to tumor control outcomes of patients with glioblastoma multiforme. Onco Targets Ther. 2016;9:1115–1122. https://doi.org/10.2147/OTT.S96509.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Mistry AM, Hale AT, Chambless LB, Weaver KD, Thompson RC, Ihrie RA. Influence of glioblastoma contact with the lateral ventricle on survival: a meta-analysis. J Neurooncol. 2017;131(1):125–33.

    Article  CAS  Google Scholar 

  27. Mistry AM, Dewan MC, White-Dzuro GA, Brinson PR, Weaver KD, Thompson RC, et al. Decreased survival in glioblastomas is specific to contact with the ventricular–subventricular zone, not subgranular zone or corpus callosum. J Neurooncol. 2017;132(2):341–9.

    Article  Google Scholar 

  28. Kappadakunnel M, Eskin A, Dong J, Nelson SF, Mischel PS, Liau LM, et al. Stem cell associated gene expression in glioblastoma multiforme: relationship to survival and the subventricular zone. J Neurooncol. 2010;96(3):359–67.

    Article  CAS  Google Scholar 

  29. Liang TH-K, Kuo S-H, Wang C-W, Chen W-Y, Hsu C-Y, Lai S-F, et al. Adverse prognosis and distinct progression patterns after concurrent chemoradiotherapy for glioblastoma with synchronous subventricular zone and corpus callosum invasion. Radiother Oncol. 2016;118(1):16–23.

    Article  Google Scholar 

  30. Lee SW, Fraass BA, Marsh LH, Herbort K, Gebarski SS, Martel MK, et al. Patterns of failure following high-dose 3-D conformal radiotherapy for high-grade astrocytomas: a quantitative dosimetric study. Int J Radiat Oncol Biol Phys. 1999;43(1):79–88.

    Article  CAS  Google Scholar 

  31. Brandes AA, Tosoni A, Franceschi E, Sotti G, Frezza G, Amistà P, et al. Recurrence pattern after temozolomide concomitant with and adjuvant to radiotherapy in newly diagnosed patients with glioblastoma: correlation with MGMT promoter methylation status. J Clin Oncol. 2009;27(8):1275–9.

    Article  CAS  Google Scholar 

  32. Macdonald DR, Cascino TL, Schold SC, Cairncross JG. Response criteria for phase II studies of supratentorial malignant glioma. J Clin Oncol. 1990;8(7):1277–80.

    Article  CAS  Google Scholar 

  33. Sherriff J, Tamangani J, Senthil L, Cruickshank G, Spooner D, Jones B, et al. Patterns of relapse in glioblastoma multiforme following concomitant chemoradiotherapy with temozolomide. Br J Radiol. 2013;86(1022):20120414.

    Article  CAS  Google Scholar 

  34. Oh J, Sahgal A, Sanghera P, Tsao MN, Davey P, Lam K, et al. Glioblastoma: patterns of recurrence and efficacy of salvage treatments. Can J Neurol Sci. 2011;38(4):621–5.

    Article  Google Scholar 

  35. Chamberlain MC. Radiographic patterns of relapse in glioblastoma. J Neurooncol. 2011;101(2):319–23.

    Article  Google Scholar 

  36. Baldock AL, Rockne RC, Boone AD, et al. From patient-specific mathematical neuro-oncology to precision medicine. Front Oncol. 2013;3:62. https://doi.org/10.3389/fonc.2013.00062(published 2013 Apr 2).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Wick W, Stupp R, Beule AC, et al. A novel tool to analyze MRI recurrence patterns in glioblastoma. Neuro Oncol. 2008;10(6):1019–24. https://doi.org/10.1215/15228517-2008-058.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Han S, Li X, Qiu B, Jiang T, Wu A. Can lateral ventricle contact predict the ontogeny and prognosis of glioblastoma? J Neurooncol. 2015;124(1):45–55.

    Article  CAS  Google Scholar 

  39. Batista KMP, Vega IF, de Eulate-Beramendi SA, Morales JCG, Kurbanov A, Asnel D, et al. Original article prognostic significance of the markers IDH1 and YKL40 related to the subventricular zone. Folia Neuropathol. 2015;1:52–9.

    Article  Google Scholar 

Download references

Acknowledgements

The authors wish to thank Bradley Londres for professional English language editing.

Author information

Authors and Affiliations

  1. Radiation Oncology, Institut Català D’Oncologia, c/ del Canyet SN, 08916, Badalona, Catalonia, Spain

    S. Comas & S. Villà

  2. Physics, Institut Català D’Oncologia, Badalona, Catalonia, Spain

    E. Luguera & J. Molero

  3. Medical Oncology, Institut Català D’Oncologia, Badalona, Catalonia, Spain

    C. Balaña & A. Estival

  4. Neuroradiology, Institut de Diagnòstic Per La Imatge, Badalona, Catalonia, Spain

    S. Castañer

  5. Pathology. Hospital Universitari Germans Trias I Pujol, Badalona, Catalonia, Spain

    C. Carrato

  6. Neurosurgery. Hospital Universitari Germans Trias I Pujol, Badalona, Catalonia, Spain

    C. Hostalot & P. Teixidor

  7. Universitat Autònoma de Barcelona, Badalona, Catalonia, Spain

    S. Villà

Authors
  1. S. Comas
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. E. Luguera
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J. Molero
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. C. Balaña
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A. Estival
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. S. Castañer
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. C. Carrato
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. C. Hostalot
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. P. Teixidor
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. S. Villà
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to S. Villà.

Ethics declarations

Conflict of interest

The authors declare no competing interests related to the present study or manuscript.

Availability of data and materials

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Comas, S., Luguera, E., Molero, J. et al. Influence of glioblastoma contact with the subventricular zone on survival and recurrence patterns. Clin Transl Oncol 23, 554–564 (2021). https://doi.org/10.1007/s12094-020-02448-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12094-020-02448-x

Keywords

Search

Navigation