Influence of wide opening of the lateral ventricle on survival for supratentorial glioblastoma patients with radiotherapy and concomitant temozolomide-based chemotherapy

  • Taiichi SaitoEmail author
  • Yoshihiro Muragaki
  • Takashi Maruyama
  • Takashi Komori
  • Masayuki Nitta
  • Shunsuke Tsuzuki
  • Atsushi Fukui
  • Takakazu Kawamata
Original Article


The prognosis for glioblastoma (GBM) varies among patients. Ventricular opening during surgery has been reported as a prognostic factor for GBM patients, but the influence of ventricular opening itself on patient prognosis remains controversial. We presumed that the degree of ventricular opening would correlate with the degree of subventricular zone (SVZ) resection and with prognosis in GBM patients. This study therefore investigated whether the degree of ventricular opening correlates with prognosis in GBM patients treated with the standard protocol of chemo-radiotherapy. Participants comprised 111 patients with newly diagnosed GBM who underwent surgery and received postoperative radiotherapy and temozolomide-based chemotherapy from 2005 to 2018. We classified 111 patients into “No ventricular opening (NVO)”, “Ventricular opening, small (VOS; distance < 23.2 mm)”, and “Ventricular opening, wide (VOW; distance ≥ 23.2 mm)” groups. We evaluated the relationship between degree of ventricular opening and prognosis using survival analyses that included other clinicopathological factors. Log-rank testing revealed age, Karnofsky performance status (KPS), extent of resection, O6-methylguanine-DNA methyltransferase (MGMT) status, isocitrate dehydrogenase (IDH)1 mutation, and degree of ventricular opening correlated significantly with overall survival. Multivariate analysis identified the degree of ventricular opening (small vs. wide) as the most significant prognostic factor (hazard ratio = 3.674; p < 0.0001). We demonstrated that wide opening of the lateral ventricle (LV) contributes to longer survival compared with small opening among GBM patients. Our results indicate that wide opening of the LV may correlate with the removal of a larger proportion of tumor stem cells from the SVZ.


Lateral ventricle Glioblastoma Subventricular zone Prognosis Temozolomide 



We thank Takashi Sakayori and Asuka Komori, Department of Pathology, Tokyo Women’s Medical University, Tokyo, Japan, for the immunohistochemical staining and the molecular genetic analyses, and Soko Ikuta, Faculty of Advanced Techno-Surgery, Institute of Advanced Biomedical Engineering and Science, Tokyo Women’s Medical University, for the data analyses of patients’ clinical characteristics.

Funding information

This study was supported by the Japan Society for the Promotion of Science (JSPS) KAKENHI Grant No. 18 K09006.

Compliance with ethical standards

Ethical approval

Ethical approval was obtained from the ethics committee at Tokyo Women’s Medical University (No. 3540).

Statement of informed consent

Given the retrospective design, the institutional review board waived the requirement for informed consent. We took the opt-out method. To protect patient privacy, we removed all identifiers from our records upon completion of our analyses.

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Adeberg S, Bostel T, Konig L, Welzel T, Debus J, Combs SE (2014) A comparison of long-term survivors and short-term survivors with glioblastoma, subventricular zone involvement: a predictive factor for survival? Radiat Oncol 9:95. CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Ahmadipour Y, Jabbarli R, Gembruch O, Pierscianek D, Darkwah Oppong M, Dammann P, Wrede K, Ozkan N, Muller O, Sure U, El Hindy N (2019) Impact of multifocality and molecular markers on survival of glioblastoma. World Neurosurg 122:e461–e466. 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. CrossRefGoogle Scholar
  4. 4.
    Behling F, Kaltenstadler M, Noell S, Schittenhelm J, Bender B, Eckert F, Tabatabai G, Tatagiba M, Skardelly M (2017) The prognostic impact of ventricular opening in glioblastoma surgery: a retrospective single center analysis. World Neurosurg 106:615–624. CrossRefPubMedGoogle Scholar
  5. 5.
    Fukui A, Muragaki Y, Saito T, Maruyama T, Nitta M, Ikuta S, Kawamata T (2017) Volumetric analysis using low-field intraoperative magnetic resonance imaging for 168 newly diagnosed supratentorial glioblastomas: effects of extent of resection and residual tumor volume on survival and recurrence. World Neurosurg 98:73–80. CrossRefPubMedGoogle Scholar
  6. 6.
    Gong X, Schwartz PH, Linskey ME, Bota DA (2011) Neural stem/progenitors and glioma stem-like cells have differential sensitivity to chemotherapy. Neurology 76:1126–1134. CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Han S, Li X, Qiu B, Jiang T, Wu A (2015) Can lateral ventricle contact predict the ontogeny and prognosis of glioblastoma? J Neuro-Oncol 124:45–55. CrossRefGoogle Scholar
  8. 8.
    Hegi ME, Diserens AC, Gorlia T, Hamou MF, de Tribolet N, Weller M, Kros JM, Hainfellner JA, Mason W, Mariani L, Bromberg JE, Hau P, Mirimanoff RO, Cairncross JG, Janzer RC, Stupp R (2005) MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 352:997–1003. CrossRefPubMedGoogle Scholar
  9. 9.
    Jafri NF, Clarke JL, Weinberg V, Barani IJ, Cha S (2013) Relationship of glioblastoma multiforme to the subventricular zone is associated with survival. Neuro-Oncology 15:91–96. CrossRefPubMedGoogle Scholar
  10. 10.
    Jeremic B, Milicic B, Grujicic D, Dagovic A, Aleksandrovic J (2003) Multivariate analysis of clinical prognostic factors in patients with glioblastoma multiforme treated with a combined modality approach. J Cancer Res Clin Oncol 129:477–484. CrossRefPubMedGoogle Scholar
  11. 11.
    John JK, Robin AM, Pabaney AH, Rammo RA, Schultz LR, Sadry NS, Lee IY (2017) Complications of ventricular entry during craniotomy for brain tumor resection. J Neurosurg 127:426–432. CrossRefPubMedGoogle Scholar
  12. 12.
    Jungk C, Warta R, Mock A, Friauf S, Hug B, Capper D, Abdollahi A, Debus J, Bendszus M, von Deimling A, Unterberg A, Herold-Mende C (2019) Location-dependent patient outcome and recurrence patterns in IDH1-wildtype glioblastoma. Cancers (Basel) 11. CrossRefGoogle Scholar
  13. 13.
    Lacroix M, Abi-Said D, Fourney DR, Gokaslan ZL, Shi W, DeMonte F, Lang FF, McCutcheon IE, Hassenbusch SJ, Holland E, Hess K, Michael C, Miller D, Sawaya R (2001) A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival. J Neurosurg 95:190–198. CrossRefPubMedGoogle Scholar
  14. 14.
    Lam N, Chambers CR (2012) Temozolomide plus radiotherapy for glioblastoma in a Canadian province: efficacy versus effectiveness and the impact of O6-methylguanine-DNA-methyltransferase promoter methylation. J Oncol Pharm Pract 18:229–238. CrossRefPubMedGoogle Scholar
  15. 15.
    Lee JH, Lee JE, Kahng JY, Kim SH, Park JS, Yoon SJ, Um JY, Kim WK, Lee JK, Park J, Kim EH, Lee JH, Lee JH, Chung WS, Ju YS, Park SH, Chang JH, Kang SG, Lee JH (2018) Human glioblastoma arises from subventricular zone cells with low-level driver mutations. Nature 560:243–247. CrossRefPubMedGoogle Scholar
  16. 16.
    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-Oncology 9:424–429. CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Matsuda M, Kohzuki H, Ishikawa E, Yamamoto T, Akutsu H, Takano S, Mizumoto M, Tsuboi K, Matsumura A (2018) Prognostic analysis of patients who underwent gross total resection of newly diagnosed glioblastoma. J Clin Neurosci 50:172–176. CrossRefPubMedGoogle Scholar
  18. 18.
    Mistry AM, Dewan MC, White-Dzuro GA, Brinson PR, Weaver KD, Thompson RC, Ihrie RA, Chambless LB (2017) Decreased survival in glioblastomas is specific to contact with the ventricular-subventricular zone, not subgranular zone or corpus callosum. J Neuro-Oncol 132:341–349. CrossRefGoogle Scholar
  19. 19.
    Mistry AM, Hale AT, Chambless LB, Weaver KD, Thompson RC, Ihrie RA (2017) Influence of glioblastoma contact with the lateral ventricle on survival: a meta-analysis. J Neuro-Oncol 131:125–133. CrossRefGoogle Scholar
  20. 20.
    Muragaki Y, Iseki H, Maruyama T, Kawamata T, Yamane F, Nakamura R, Kubo O, Takakura K, Hori T (2006) Usefulness of intraoperative magnetic resonance imaging for glioma surgery. Acta Neurochir Suppl 98:67–75CrossRefGoogle Scholar
  21. 21.
    Muragaki Y, Iseki H, Maruyama T, Tanaka M, Shinohara C, Suzuki T, Yoshimitsu K, Ikuta S, Hayashi M, Chernov M, Hori T, Okada Y, Takakura K (2011) Information-guided surgical management of gliomas using low-field-strength intraoperative MRI. Acta Neurochir Suppl 109:67–72. CrossRefPubMedGoogle Scholar
  22. 22.
    Nitta M, Muragaki Y, Maruyama T, Iseki H, Komori T, Ikuta S, Saito T, Yasuda T, Hosono J, Okamoto S, Koriyama S, Kawamata T (2018) Role of photodynamic therapy using talaporfin sodium and a semiconductor laser in patients with newly diagnosed glioblastoma. J Neurosurg:1–8. CrossRefGoogle Scholar
  23. 23.
    Nourallah B, Digpal R, Jena R, Watts C (2017) Irradiating the subventricular zone in glioblastoma patients: is there a case for a clinical trial? Clin Oncol (R Coll Radiol) 29:26–33. CrossRefGoogle Scholar
  24. 24.
    Parsons DW, Jones S, Zhang X, Lin JC, Leary RJ, Angenendt P, Mankoo P, Carter H, Siu IM, Gallia GL, Olivi A, McLendon R, Rasheed BA, Keir S, Nikolskaya T, Nikolsky Y, Busam DA, Tekleab H, Diaz LA Jr, Hartigan J, Smith DR, Strausberg RL, Marie SK, Shinjo SM, Yan H, Riggins GJ, Bigner DD, Karchin R, Papadopoulos N, Parmigiani G, Vogelstein B, Velculescu VE, Kinzler KW (2008) An integrated genomic analysis of human glioblastoma multiforme. Science 321:1807–1812. CrossRefPubMedPubMedCentralGoogle 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 53:52–59CrossRefGoogle Scholar
  26. 26.
    Quillien V, Lavenu A, Karayan-Tapon L, Carpentier C, Labussiere M, Lesimple T, Chinot O, Wager M, Honnorat J, Saikali S, Fina F, Sanson M, Figarella-Branger D (2012) Comparative assessment of 5 methods (methylation-specific polymerase chain reaction, MethyLight, pyrosequencing, methylation-sensitive high-resolution melting, and immunohistochemistry) to analyze O6-methylguanine-DNA-methyltranferase in a series of 100 glioblastoma patients. Cancer 118:4201–4211. CrossRefPubMedGoogle Scholar
  27. 27.
    Roh TH, Kang SG, Moon JH, Sung KS, Park HH, Kim SH, Kim EH, Hong CK, Suh CO, Chang JH (2019) Survival benefit of lobectomy over gross-total resection without lobectomy in cases of glioblastoma in the noneloquent area: a retrospective study. J Neurosurg:1–7.
  28. 28.
    Saito T, Sugiyama K, Takeshima Y, Amatya VJ, Yamasaki F, Takayasu T, Nosaka R, Muragaki Y, Kawamata T, Kurisu K (2018) Prognostic implications of the subcellular localization of survivin in glioblastomas treated with radiotherapy plus concomitant and adjuvant temozolomide. J Neurosurg 128:679–684. CrossRefPubMedGoogle Scholar
  29. 29.
    Saito T, Muragaki Y, Shioyama T, Komori T, Maruyama T, Nitta M, Yasuda T, Hosono J, Okamoto S, Kawamata T (2019) Malignancy index using intraoperative flow cytometry is a valuable prognostic factor for glioblastoma treated with radiotherapy and concomitant temozolomide. Neurosurgery 84:662–672. CrossRefPubMedGoogle Scholar
  30. 30.
    Sanai N, Alvarez-Buylla A, Berger MS (2005) Neural stem cells and the origin of gliomas. N Engl J Med 353:811–822. CrossRefPubMedGoogle Scholar
  31. 31.
    Sanai N, Polley MY, McDermott MW, Parsa AT, Berger MS (2011) An extent of resection threshold for newly diagnosed glioblastomas. J Neurosurg 115:3-8. Doi:
  32. 32.
    Senft C, Bink A, Franz K, Vatter H, Gasser T, Seifert V (2011) Intraoperative MRI guidance and extent of resection in glioma surgery: a randomised, controlled trial. Lancet Oncol 12:997–1003. CrossRefPubMedGoogle Scholar
  33. 33.
    Sonoda Y, Shibahara I, Matsuda KI, Saito R, Kawataki T, Oda M, Sato Y, Sadahiro H, Nomura S, Sasajima T, Beppu T, Kanamori M, Sakurada K, Kumabe T, Tominaga T, Kinouchi H, Shimizu H, Ogasawara K, Suzuki M (2017) Opening the ventricle during surgery diminishes survival among patients with newly diagnosed glioblastoma treated with carmustine wafers: a multi-center retrospective study. J Neuro-Oncol 134:83–88. CrossRefGoogle Scholar
  34. 34.
    Stummer W, Pichlmeier U, Meinel T, Wiestler OD, Zanella F, Reulen HJ, Group AL-GS (2006) Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial. Lancet Oncol 7:392–401. CrossRefPubMedGoogle Scholar
  35. 35.
    Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, 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. N Engl J Med 352:987–996. CrossRefGoogle Scholar
  36. 36.
    van Dijken BRJ, Jan van Laar P, Li C, Yan JL, Boonzaier NR, Price SJ, van der Hoorn A (2018) Ventricle contact is associated with lower survival and increased peritumoral perfusion in glioblastoma. J Neurosurg:1–7. CrossRefGoogle Scholar
  37. 37.
    Weller M, Felsberg J, Hartmann C, Berger H, Steinbach JP, Schramm J, Westphal M, Schackert G, Simon M, Tonn JC, Heese O, Krex D, Nikkhah G, Pietsch T, Wiestler O, Reifenberger G, von Deimling A, Loeffler M (2009) Molecular predictors of progression-free and overall survival in patients with newly diagnosed glioblastoma: a prospective translational study of the German Glioma Network. J Clin Oncol 27:5743–5750. CrossRefPubMedGoogle Scholar
  38. 38.
    Woo P, Ho J, Lam S, Ma E, Chan D, Wong WK, Mak C, Lee M, Wong ST, Chan KY, Poon WS (2018) A comparative analysis of the usefulness of survival prediction models for patients with glioblastoma in the temozolomide era: the importance of methylguanine methyltransferase promoter methylation, extent of resection, and subventricular zone location. World Neurosurg 115:e375–e385. CrossRefPubMedGoogle Scholar
  39. 39.
    Yan H, Parsons DW, Jin G, McLendon R, Rasheed BA, Yuan W, Kos I, Batinic-Haberle I, Jones S, Riggins GJ, Friedman H, Friedman A, Reardon D, Herndon J, Kinzler KW, Velculescu VE, Vogelstein B, Bigner DD (2009) IDH1 and IDH2 mutations in gliomas. N Engl J Med 360:765–773. CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    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 Neuro-Oncol 104:261–269. CrossRefGoogle Scholar
  41. 41.
    Zou P, Xu H, Chen P, Yan Q, Zhao L, Zhao P, Gu A (2013) IDH1/IDH2 mutations define the prognosis and molecular profiles of patients with gliomas: a meta-analysis. PLoS One 8:e68782. CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of NeurosurgeryTokyo Women’s Medical UniversityTokyoJapan
  2. 2.Faculty of Advanced Techno-SurgeryTokyo Women’s Medical UniversityTokyoJapan
  3. 3.Department of Laboratory Medicine and Pathology (Neuropathology)Tokyo Metropolitan Neurological HospitalTokyoJapan

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