Journal of Neuro-Oncology

, Volume 142, Issue 2, pp 253–261 | Cite as

Supratentorial high-grade astrocytoma with leptomeningeal spread to the fourth ventricle: a lethal dissemination with dismal prognosis

  • Mingxiao Li
  • Xiaohui Ren
  • Haihui Jiang
  • Kaiyuan Yang
  • Wei Huang
  • Kefu Yu
  • Hongyan Chen
  • Gehong Dong
  • Yong Cui
  • Song LinEmail author
Clinical Study



Leptomeningeal spread to the fourth ventricle (LSFV) from supratentorial high-grade astrocytoma (HGA) is rarely investigated. The incidence and prognostic merit of LSFV were analyzed in this study.


A consecutive cohort of 175 patients with pathologically diagnosed HGA according to the 2016 WHO classification of brain tumors was enrolled. LSFV was defined as radiological occupation in the fourth ventricle at the moment of initial progression. Clinical, radiological, and pathological data were analyzed to explore the difference between HGA patients with and without LSFV.


There were 18 of 175 (10.3%) HGAs confirmed with LSFV. The difference of survival rate between patients with LSFV or not was significant in both overall survival (OS) (14.5 vs. 24 months, P =  0.0007) and post progression survival (PPS) (6.0 vs. 11.5 months, P = 0.0004), while no significant difference was observed in time to progression (TTP) (8.5 months vs. 9.5 months P = 0.6795). In the Cox multivariate analysis, LSFV was confirmed as an independent prognostic risk factor for OS (HR 2.06, P = 0.010). LSFV was correlated with younger age (P = 0.044), ventricle infringement of primary tumor (P < 0.001) and higher Ki-67 index (P = 0.013) in further analysis, and the latter two have been validated in the Logistic regression analysis (OR 18.16, P = 0.006; OR 4.04, P = 0.012, respectively).


LSFV was indicative of end-stage for supratentorial HGA patients, which shortened patients’ PPS and OS instead of TTP. It’s never too cautious to alert this lethal event when tumor harbored ventricle infringement and higher Ki-67 index in routine clinical course.


High-grade astrocytoma The fourth ventricle Dissemination Prognosis 



It’s extremely precious that the patients rigorously performed every follow-up in our department, which provided us accurate materials for this analysis. The authors sincerely thank the patients and their families for their participation in the present study.


This study was funded by National Natural Science Foundation of China (81571632).

Compliance with ethical standards

Conflict of interest

No potential conflicts of interest were disclosed.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the Capital Medical University and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

11060_2018_3086_MOESM1_ESM.jpg (128 kb)
Supplementary material 1 (JPG 128 KB)
11060_2018_3086_MOESM2_ESM.docx (15 kb)
Supplementary material 2 (DOCX 15 KB)


  1. 1.
    Wen PY, Kesari S (2008) Malignant gliomas in adults. N Engl J Med 359(5):492–507CrossRefGoogle Scholar
  2. 2.
    Behin A, Hoang-Xuan K, Carpentier AF, Delattre JY (2003) Primary brain tumours in adults. Lancet 361(9354):323–331. CrossRefGoogle Scholar
  3. 3.
    Rick J, Chandra A, Aghi MK (2018) Tumor treating fields: a new approach to glioblastoma therapy. J Neurooncol. Google Scholar
  4. 4.
    Lim M, Xia Y, Bettegowda C, Weller M (2018) Current state of immunotherapy for glioblastoma. Nat Rev Clin Oncol 15(7):422–442. CrossRefGoogle Scholar
  5. 5.
    Weathers SS, Gilbert MR (2017) Toward personalized targeted therapeutics: an overview. Neurotherapeutics 14(2):256–264. CrossRefGoogle Scholar
  6. 6.
    Pope WB, Xia Q, Paton VE, Das A, Hambleton J, Kim HJ, Huo J, Brown MS, Goldin J, Cloughesy T (2011) Patterns of progression in patients with recurrent glioblastoma treated with bevacizumab. Neurology 76(5):432–437CrossRefGoogle Scholar
  7. 7.
    Fujimura M, Kumabe T, Jokura H, Shirane R, Yoshimoto T, Tominaga T (2004) Intractable vomiting as an early clinical symptom of cerebrospinal fluid seeding to the fourth ventricle in patients with high-grade astrocytoma. J Neuro-Oncol 66(1–2):209–216CrossRefGoogle Scholar
  8. 8.
    Burger MC, Zeiner PS, Jahnke K, Wagner M, Mittelbronn M, Steinbach JP (2016) Addition of anti-angiogenetic therapy with bevacizumab to chemo- and radiotherapy for leptomeningeal metastases in primary brain tumors. PLoS ONE 11(6):e0155315. CrossRefGoogle Scholar
  9. 9.
    Zhang Z, Jiang H, Chen X, Bai J, Cui Y, Ren X, Chen X, Wang J, Zeng W, Lin S (2014) Identifying the survival subtypes of glioblastoma by quantitative volumetric analysis of MRI. J Neurooncol 119(1):207–214. CrossRefGoogle Scholar
  10. 10.
    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(4):424–429CrossRefGoogle Scholar
  11. 11.
    Kuhnt D, Becker A, Ganslandt O, Bauer M, Buchfelder M, Nimsky C (2011) Correlation of the extent of tumor volume resection and patient survival in surgery of glioblastoma multiforme with high-field intraoperative MRI guidance. Neuro Oncol 13(12):1339–1348. CrossRefGoogle Scholar
  12. 12.
    Jiang H, Cui Y, Liu X, Ren X, Lin S (2017) Patient-specific resection strategy of glioblastoma multiforme: choice based on a preoperative scoring scale. Ann Surg Oncol 24(7):2006–2014. CrossRefGoogle Scholar
  13. 13.
    Iwamoto FM, Abrey LE, Beal K, Gutin PH, Rosenblum MK, Reuter VE, Deangelis LM, Lassman AB (2009) Patterns of relapse and prognosis after bevacizumab failure in recurrent glioblastoma. Neurology 73(15):1239–1241CrossRefGoogle Scholar
  14. 14.
    Jiang H, Zhang Z, Ren X, Zeng W, Jia W, Wang J, Lin S (2014) 1p/19q-driven prognostic molecular classification for high-grade oligodendroglial tumors. J Neurooncol 120(3):607–614. CrossRefGoogle Scholar
  15. 15.
    Jiang H, Ren X, Wang J, Zhang Z, Jia W, Lin S (2014) Short-term survivors in glioblastomas with oligodendroglioma component: a clinical study of 186 Chinese patients from a single institution. J Neurooncol 116(2):395–404. CrossRefGoogle Scholar
  16. 16.
    Cai X, Qin JJ, Hao SY, Li H, Zeng C, Sun SJ, Yu LB, Gao ZX, Xie J (2018) Clinical characteristics associated with the intracranial dissemination of gliomas. Clin Neurol Neurosurg 166:141–146. CrossRefGoogle Scholar
  17. 17.
    Wen PY, Macdonald DR, Reardon DA, Cloughesy TF, Sorensen AG, Galanis E, Degroot J, Wick W, Gilbert MR, Lassman AB, Tsien C, Mikkelsen T, Wong ET, Chamberlain MC, Stupp R, Lamborn KR, Vogelbaum MA, van den Bent MJ, Chang SM (2010) Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group. J Clin Oncol 28(11):1963–1972. CrossRefGoogle Scholar
  18. 18.
    Cohen ZR, Hassenbusch SJ, Maor MH, Pfeffer RM, Ram Z (2002) Intractable vomiting from glioblastoma metastatic to the fourth ventricle: three case studies. Neuro-Oncology 4(2):129–133CrossRefGoogle Scholar
  19. 19.
    Khan MN, Poulin A, Essig M (2017) Fourth Ventricular lesions in metastatic gliomas: a rare predilection? Brain Tumor Res Treat 5(1):24–29. CrossRefGoogle Scholar
  20. 20.
    de Groot JF, Fuller G, Kumar AJ, Piao Y, Eterovic K, Ji Y, Conrad CA (2010) Tumor invasion after treatment of glioblastoma with bevacizumab: radiographic and pathologic correlation in humans and mice. Neuro-oncology 12(3):233CrossRefGoogle Scholar
  21. 21.
    Arita N, Taneda M, Hayakawa T (1994) Leptomeningeal dissemination of malignant gliomas. Incidence, diagnosis and outcome. Acta Neurochir (Wien) 126(2–4):84–92CrossRefGoogle Scholar
  22. 22.
    Noh JH, Lee MH, Kim WS, Lim DH, Kim ST, Kong DS, Nam DH, Lee JI, Seol HJ (2015) Optimal treatment of leptomeningeal spread in glioblastoma: analysis of risk factors and outcome. Acta Neurochir (Wien) 157(4):569–576. CrossRefGoogle Scholar
  23. 23.
    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. CrossRefGoogle Scholar
  24. 24.
    Gai X, Li S, Wei Y, Yu S (2018) A case report about oligodendrogliomas of the fourth ventricle. Med (Baltimore) 97(17):e0594. CrossRefGoogle Scholar
  25. 25.
    Perry JR, Laperriere N, Mason WP (2017) Radiation plus temozolomide in patients with glioblastoma. N Engl J Med 376(22):2197. CrossRefGoogle Scholar
  26. 26.
    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(8):699–708. CrossRefGoogle Scholar
  27. 27.
    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(8):765–773. CrossRefGoogle Scholar
  28. 28.
    Baker H (2015) Radiotherapy in the elderly and frail with glioblastoma. Lancet Oncol 16(15):e530. CrossRefGoogle Scholar
  29. 29.
    VandenDriessche T, Chuah MK (2013) Glioblastoma: bridging the gap with gene therapy. Lancet Oncol 14(9):789–790. CrossRefGoogle Scholar
  30. 30.
    Okawa S, Gagrica S, Blin C, Ender C, Pollard SM, Krijgsveld J (2017) Proteome and secretome characterization of glioblastoma-derived neural stem cells. Stem cells (Dayton Ohio) 35(4):967–980. CrossRefGoogle Scholar
  31. 31.
    Qin EY, Cooper DD, Abbott KL, Lennon J, Nagaraja S, Mackay A, Jones C, Vogel H, Jackson PK, Monje M (2017) Neural precursor-derived pleiotrophin mediates subventricular zone invasion by glioma. Cell 170(5):845–859 e819. CrossRefGoogle Scholar
  32. 32.
    Goffart N, Lombard A, Lallemand F, Kroonen J, Nassen J, Di Valentin E, Berendsen S, Dedobbeleer M, Willems E, Robe P, Bours V, Martin D, Martinive P, Maquet P, Rogister B (2017) CXCL12 mediates glioblastoma resistance to radiotherapy in the subventricular zone. Neuro-Oncology 19(1):66–77. CrossRefGoogle Scholar
  33. 33.
    Roelz R, Reinacher P, Jabbarli R, Kraeutle R, Hippchen B, Egger K, Weyerbrock A, Machein M (2015) Surgical Ventricular entry is a key risk factor for leptomeningeal metastasis of high grade gliomas. Sci Rep 5:17758. CrossRefGoogle Scholar
  34. 34.
    Mistry AM, Kelly PD, Thompson RC, Chambless LB (2018) Cancer dissemination, hydrocephalus, and survival after cerebral ventricular entry during high-grade glioma surgery: a meta-analysis. Neurosurgery. Google Scholar
  35. 35.
    Li Y, Qian Z, Xu K, Wang K, Fan X, Li S, Liu X, Wang Y, Jiang T (2017) Radiomic features predict Ki-67 expression level and survival in lower grade gliomas. J Neurooncol 135(2):317–324. CrossRefGoogle Scholar
  36. 36.
    Rezai AR, Woo HH, Lee M, Cohen H, Zagzag D, Epstein FJ (1996) Disseminated ependymomas of the central nervous system. J Neurosurg 85(4):618–624. CrossRefGoogle Scholar
  37. 37.
    Kato H, Fujimura M, Kumabe T, Ishioka C, Kanamaru R, Yoshimoto T (2004) PTEN gene mutation and high MIB-1 labeling index may contribute to dissemination in patients with glioblastoma. J Clin Neurosci 11(1):37–41. CrossRefGoogle Scholar
  38. 38.
    Pasquale DB, Carmelo A, Angelo P, Alba F, Mario B, Silvia C, Libero L, Giulio M, Annunziato MJCN (2013) The influence of surgery on recurrence pattern of glioblastoma. Neurosurgery 115(1):37–43Google Scholar
  39. 39.
    Rapp M, Baernreuther J, Turowski B, Steiger HJ, Sabel M, Kamp MA (2017) Recurrence pattern analysis of primary glioblastoma. World Neurosurg 103:733–740. CrossRefGoogle Scholar
  40. 40.
    Burger MC, Ronellenfitsch MW, Lorenz NI, Wagner M, Voss M, Capper D, Tzaridis T, Herrlinger U, Steinbach JP, Stoffels G, Langen KJ, Brandts C, Senft C, Harter PN, Bahr O (2017) Dabrafenib in patients with recurrent, BRAF V600E mutated malignant glioma and leptomeningeal disease. Oncol Rep 38(6):3291–3296. Google Scholar
  41. 41.
    Nandipati S, Demopoulos A (2011) Leptomeningeal dissemination of anaplastic glioma: prolonged survival in two patients treated with temozolomide. J Neurooncol 105(3):663–665. CrossRefGoogle Scholar
  42. 42.
    Smith JS, Parney IF, Lamborn KR, Mcdermott MW, Sneed PK, Chang SM (2007) Treatment for posterior fossa dissemination of primary supratentorial glioma. J Neurosurg 106(4):567–574CrossRefGoogle Scholar
  43. 43.
    Okita Y, Nonaka M, Umehara T, Kanemura Y, Kodama Y, Mano M, Nakajima S (2015) Efficacy of temozolomide and bevacizumab for the treatment of leptomeningeal dissemination of recurrent glioblastoma: a case report. Oncol Lett 9(4):1885–1888. CrossRefGoogle Scholar
  44. 44.
    Linsenmann T, Monoranu CM, Vince GH, Westermaier T, Hagemann C, Kessler AF, Ernestus RI, Lohr M (2014) Long-term tumor control of spinal dissemination of cerebellar glioblastoma multiforme by combined adjuvant bevacizumab antibody therapy: a case report. BMC Res Notes 7:496. CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Neurosurgery, Beijing Tiantan HospitalCapital Medical UniversityBeijingChina
  2. 2.Department of Pharmacy, Beijing Tiantan HospitalCapital Medical UniversityBeijingChina
  3. 3.Department of Radiology, Beijing Tiantan HospitalCapital Medical UniversityBeijingChina
  4. 4.Department of Pathology, Beijing Tiantan HospitalCapital Medical UniversityBeijingChina
  5. 5.National Clinical Research Center for Neurological Diseases, Center of Brain Tumor, Beijing Institute for Brain Disorders and Beijing Key Laboratory of Brian TumorBeijingChina

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