Ventricle contact is associated with lower survival and increased peritumoral perfusion in glioblastoma

Restricted access


The purpose of this study was to prospectively investigate outcome and differences in peritumoral MRI characteristics of glioblastomas (GBMs) that were in contact with the ventricles (ventricle-contacting tumors) and those that were not (noncontacting tumors). GBMs are heterogeneous tumors with variable survival. Lower survival is suggested for patients with ventricle-contacting tumors than for those with noncontacting tumors. This might be supported by aggressive peritumoral MRI features. However, differences in MRI characteristics of the peritumoral environment between ventricle-contacting and noncontacting GBMs have not yet been investigated.


Patients with newly diagnosed GBM underwent preoperative MRI with contrast-enhanced T1-weighted, FLAIR, diffusion-weighted, and perfusion-weighted sequences. Tumors were categorized into ventricle-contacting or noncontacting based on contrast enhancement. Survival analysis was performed using log-rank for univariate analysis and Cox regression for multivariate analysis. Normalized perfusion (relative cerebral blood volume [rCBV]) and diffusion (apparent diffusion coefficient [ADC]) values were calculated in 2 regions: the peritumoral nonenhancing FLAIR region overlapping the subventricular zone and the remaining peritumoral nonenhancing FLAIR region.


Overall survival was significantly lower for patients with contacting tumors than for those with noncontacting tumors (434 vs 747 days, p < 0.001). Progression-free survival showed a comparable trend (260 vs 375 days, p = 0.094). Multivariate analysis confirmed a survival difference for both overall survival (HR 3.930, 95% CI 1.740–8.875, p = 0.001) and progression-free survival (HR 2.506, 95% CI 1.254–5.007, p = 0.009). Peritumoral perfusion was higher in contacting than in noncontacting tumors for both FLAIR regions (p = 0.04). There was no difference in peritumoral ADC values between the 2 groups.


Patients with ventricle-contacting tumors had poorer outcomes than patients with noncontacting tumors. This disadvantage of ventricle contact might be explained by higher peritumoral perfusion leading to more aggressive behavior.

ABBREVIATIONS 5-ALA = 5-aminolevulinic acid; ADC = apparent diffusion coefficient; DWI = diffusion-weighted imaging; FLAIR = fluid-attenuated inversion recovery; FOV = field of view; GBM = glioblastoma; IDH = isocitrate dehydrogenase; MGMT = O6-methylguanine-DNA-methyltransferase; PWI = perfusion-weighted imaging; RANO = Response Assessment in Neuro-Oncology; rCBV = relative cerebral blood volume; SVZ = subventricular zone; TE = echo time; TI = inversion time; TR = repetition time.

Article Information

Correspondence Bart Roelf Jan van Dijken: University Medical Center Groningen, The Netherlands.

INCLUDE WHEN CITING Published online October 19, 2018; DOI: 10.3171/2018.5.JNS18340.

Disclosures The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

© AANS, except where prohibited by US copyright law.



  • View in gallery

    Regions of interest. Representative MR images obtained in a patient with a ventricle-contacting glioblastoma (upper row) and a patient with a noncontacting glioblastoma (lower row). A and D: Contrast-enhanced T1 weighted images with a 5-mm SVZ surrounding the ventricles (blue). B and E: FLAIR images. The overlap between the high FLAIR signal and the SVZ was included as the first region of interest (yellow). C and F: The remaining high FLAIR signal outside the T1 contrast-enhancing lesion without SVZ overlap was included as the peritumoral region of interest (red).

  • View in gallery

    Kaplan-Meier survival curves for patients with ventricle-contacting and noncontacting GBMs. Survival curves for patients with ventricle-contacting tumors (solid line) and noncontacting tumors (dashed line). A: Overall survival. B: Progression-free survival. C: Survival after progression. Survival in days is displayed on the x-axis, with cumulative survival shown on the y-axis.



Abdullah KGRamayya AThawani JPMacyszyn LMartinez-Lage MO’Rourke DM: Factors associated with increased survival after surgical resection of glioblastoma in octogenarians. PLoS One 10:e01272022015


Adeberg SKönig LBostel THarrabi SWelzel TDebus J: Glioblastoma recurrence patterns after radiation therapy with regard to the subventricular zone. Int J Radiat Oncol Biol Phys 90:8868932014


Babu RKomisarow JMAgarwal VJRahimpour SIyer ABritt D: Glioblastoma in the elderly: the effect of aggressive and modern therapies on survival. J Neurosurg 124:99810072016


Bao SWu QSathornsumetee SHao YLi ZHjelmeland AB: Stem cell-like glioma cells promote tumor angiogenesis through vascular endothelial growth factor. Cancer Res 66:784378482006


Bohman LESwanson KRMoore JLRockne RMandigo CHankinson T: Magnetic resonance imaging characteristics of glioblastoma multiforme: implications for understanding glioma ontogeny. Neurosurgery 67:131913282010


Boonzaier NRLarkin TJMatys Tvan der Hoorn AYan JLPrice SJ: Multiparametric MR imaging of diffusion and perfusion in contrast-enhancing and nonenhancing components in patients with glioblastoma. Radiology 284:1801902017


Chaichana KParker SOlivi AQuiñones-Hinojosa A: A proposed classification system that projects outcomes based on preoperative variables for adult patients with glioblastoma multiforme. J Neurosurg 112:99710042010


Chen JLi YYu TSMcKay RMBurns DKKernie SG: A restricted cell population propagates glioblastoma growth after chemotherapy. Nature 488:5225262012


Chen LGuerrero-Cazares HYe XFord EMcNutt TKleinberg L: Increased subventricular zone radiation dose correlates with survival in glioblastoma patients after gross total resection. Int J Radiat Oncol Biol Phys 86:6166222013


Cordova JSShu HKGLiang ZGurbani SSCooper LADHolder CA: Whole-brain spectroscopic MRI biomarkers identify infiltrating margins in glioblastoma patients. Neuro Oncol 18:118011892016


Crawford FWKhayal ISMcGue CSaraswathy SPirzkall ACha S: Relationship of pre-surgery metabolic and physiological MR imaging parameters to survival for patients with untreated GBM. J Neurooncol 91:3373512009


D’Alessio AProietti GLama GBiamonte FLauriola LMoscato U: Analysis of angiogenesis related factors in glioblastoma, peritumoral tissue and their derived cancer stem cells. Oncotarget 7:78541785562016


Dhermain FGHau PLanfermann HJacobs AHvan den Bent MJ: Advanced MRI and PET imaging for assessment of treatment response in patients with gliomas. Lancet Neurol 9:9069202010


Doetsch FCaillé ILim DAGarcía-Verdugo JMAlvarez-Buylla A: Subventricular zone astrocytes are neural stem cells in the adult mammalian brain. Cell 97:7037161999


Eidel OBurth SNeumann JOKieslich PJSahm FJungk C: Tumor infiltration in enhancing and non-enhancing parts of glioblastoma: a correlation with histopathology. PLoS One 12:e01692922017


Evers PLee PPDeMarco JAgazaryan NSayre JWSelch M: Irradiation of the potential cancer stem cell niches in the adult brain improves progression-free survival of patients with malignant glioma. BMC Cancer 10:3842010


Galli RBinda EOrfanelli UCipelletti BGritti ADe Vitis S: Isolation and characterization of tumorigenic, stem-like neural precursors from human glioblastoma. Cancer Res 64:701170212004


Han SLi XQiu BJiang TWu A: Can lateral ventricle contact predict the ontogeny and prognosis of glioblastoma? J Neurooncol 124:45552015


Jafri NFClarke JLWeinberg VBarani IJCha S: Relationship of glioblastoma multiforme to the subventricular zone is associated with survival. Neuro Oncol 15:91962013


Jain RPoisson LNarang JGutman DScarpace LHwang SN: Genomic mapping and survival prediction in glioblastoma: molecular subclassification strengthened by hemodynamic imaging biomarkers. Radiology 267:2122202013


Jain RPoisson LMGutman DScarpace LHwang SNHolder CA: Outcome prediction in patients with glioblastoma by using imaging, clinical, and genomic biomarkers: focus on the nonenhancing component of the tumor. Radiology 272:4844932014


Khalifa JTensaouti FLusque APlas BLotterie JABenouaich-Amiel A: Subventricular zones: new key targets for glioblastoma treatment. Radiat Oncol 12:672017


Kuhnt DBecker AGanslandt OBauer MBuchfelder MNimsky C: Correlation of the extent of tumor volume resection and patient survival in surgery of glioblastoma multiforme with high-field intraoperative MRI guidance. Neuro Oncol 13:133913482011


Lacroix MAbi-Said DFourney DRGokaslan ZLShi WDeMonte F: A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival. J Neurosurg 95:1901982001


Lemée JMClavreul AMenei P: Intratumoral heterogeneity in glioblastoma: don’t forget the peritumoral brain zone. Neuro Oncol 17:132213322015


Liang HKTChen WYLai SFSu MYYou SLChen LH: The extent of edema and tumor synchronous invasion into the subventricular zone and corpus callosum classify outcomes and radiation therapy strategies of glioblastomas. Int J Radiat Oncol Biol Phys 99:S187S1882017


Lim DACha SMayo MCChen MHKeles EVandenBerg S: Relationship of glioblastoma multiforme to neural stem cell regions predicts invasive and multifocal tumor phenotype. Neuro Oncol 9:4244292007


Mazaris PHong XAltshuler DSchultz LPoisson LMJain R: Key determinants of short-term and long-term glioblastoma survival: a 14-year retrospective study of patients from the Hermelin Brain Tumor Center at Henry Ford Hospital. Clin Neurol Neurosurg 120:1031122014


Mistry AMDewan MCWhite-Dzuro GABrinson PRWeaver KDThompson RC: Decreased survival in glioblastomas is specific to contact with the ventricular-subventricular zone, not subgranular zone or corpus callosum. J Neurooncol 132:3413492017


Mistry AMHale ATChambless LBWeaver KDThompson RCIhrie RA: Influence of glioblastoma contact with the lateral ventricle on survival: a meta-analysis. J Neurooncol 131:1251332017


Nestler ULutz KPichlmeier UStummer WFranz KReulen HJ: Anatomic features of glioblastoma and their potential impact on survival. Acta Neurochir (Wien) 157:1791862015


Nourallah BDigpal RJena RWatts C: Irradiating the subventricular zone in glioblastoma patients: is there a case for a clinical trial? Clin Oncol (R Coll Radiol) 29:26332017


Piccirillo SGMSpiteri ISottoriva ATouloumis ABer SPrice SJ: Contributions to drug resistance in glioblastoma derived from malignant cells in the sub-ependymal zone. Cancer Res 75:1942022015


Pina Batista KMVega IFde Eulate-Beramendi SAMorales JKurbanov AAsnel D: Prognostic significance of the markers IDH1 and YKL40 related to the subventricular zone. Folia Neuropathol 53:52592015


Price SJYoung AMHScotton WJChing JMohsen LABoonzaier NR: Multimodal MRI can identify perfusion and metabolic changes in the invasive margin of glioblastomas. J Magn Reson Imaging 43:4874942016


Roos ADing ZLoftus JCTran NL: Molecular and microenvironmental determinants of glioma stem-like cell survival and invasion. Front Oncol 7:1202017


Sanai NAlvarez-Buylla ABerger MS: Neural stem cells and the origin of gliomas. N Engl J Med 353:8118222005


Sanai NPolley MYMcDermott MWParsa ATBerger MS: An extent of resection threshold for newly diagnosed glioblastomas. J Neurosurg 115:382011


Schmainda KMZhang ZPrah MSnyder BSGilbert MRSorensen AG: Dynamic susceptibility contrast MRI measures of relative cerebral blood volume as a prognostic marker for overall survival in recurrent glioblastoma: results from the ACRIN 6677/RTOG 0625 multicenter trial. Neuro Oncol 17:114811562015


Sottoriva ASpiteri IPiccirillo SGMTouloumis ACollins VPMarioni JC: Intratumor heterogeneity in human glioblastoma reflects cancer evolutionary dynamics. Proc Natl Acad Sci U S A 110:400940142013


Stupp RMason WPvan den Bent MJWeller MFisher BTaphoorn MJB: Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:9879962005


van der Hoorn AYan JLLarkin TJBoonzaier NRMatys TPrice SJ: Posttreatment apparent diffusion coefficient changes in the periresectional area in patients with glioblastoma. World Neurosurg 92:1591652016


van Dijken BRJvan Laar PJHoltman GAvan der Hoorn A: Diagnostic accuracy of magnetic resonance imaging techniques for treatment response evaluation in patients with high-grade glioma, a systematic review and meta-analysis. Eur Radiol 27:412941442017


von Elm EAltman DGEgger MPocock SJGøtzsche PCVandenbroucke JP: The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. J Clin Epidemiol 61:3443492008


Wen PYMacdonald DRReardon DACloughesy TFSorensen AGGalanis E: Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group. J Clin Oncol 28:196319722010




All Time Past Year Past 30 Days
Abstract Views 166 166 102
Full Text Views 171 171 34
PDF Downloads 88 88 21
EPUB Downloads 0 0 0


Google Scholar