Subventricular zones: new key targets for glioblastoma treatment

Khalifa, J.; Tensaouti, F.; Lusque, Amélie; Plas, Benjamin; Lotterie, Jean-Albert; Benouaich‐Amiel, Alexandra; Uro‐Coste, Emmanuelle; Lubrano, V.; Moyal, E. Cohen-Jonathan

doi:10.1186/s13014-017-0791-2

Cited by 37 publications

(21 citation statements)

References 56 publications

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“…10,15,25 There are data suggesting that inclusion of the SVZ in radiotherapy planning has a positive effect on outcome. 9,16,22 Furthermore, the increased peritumoral perfusion of ventricle-contacting GBMs could be targeted with neurosurgery. Using rCBV maps in neurosurgical planning of ventricle-contacting GBMs could possibly change the extent of resection, thereby improving outcome for patients with these tumors.…”

Section: Discussionmentioning

confidence: 99%

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

Dijken

Laar

et al. 2019

Journal of Neurosurgery

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OBJECTIVEThe 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.METHODSPatients 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.RESULTSOverall 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.CONCLUSIONSPatients 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.

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Section: Discussionmentioning

confidence: 99%

“…We identified the SVZ as a 5-mm margin surrounding the ventricles corresponding to earlier definitions of the SVZ used by others. 9,16,22 Ventricle masks were created in GeoS (Springer-Verlag) from the preoperative contrast-enhanced T1-weighted images. Further processing was done in MATLAB (MathWorks Inc.).…”

Section: Regions Of Interestmentioning

confidence: 99%

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

Dijken

Laar

et al. 2019

Journal of Neurosurgery

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“…As loss of RND1 is involved in GSCs migration from PVZ+ tumors, known to be more aggressive than PVZ– tumors [ 19 – 21 ], we tested whether RND1 gene expression could be correlated with glioblastoma prognosis. First, we analyzed RND1 expression by RT-qPCR in normal brain tissues, in several glioblastoma cell lines and in GSCs established in our laboratory.…”

Section: Resultsmentioning

confidence: 99%

“…In relation with tumor heterogeneity, clinical data, including ours, demonstrates that relapses in glioblastoma after radio-chemotherapy are more aggressive in tumors contacting the PVZ (PVZ+) than in PVZ– tumors. PVZ+ patients progress quicker and have a decreased overall survival compared to those with tumors not contacting the PVZ (PVZ–) [ 19 – 21 ]. Moreover, we have also recently shown that contact of glioblastoma with PVZ was an independent prognosis factor of shorter progressive free survival after re-irradiation [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

RND1 regulates migration of human glioblastoma stem-like cells according to their anatomical localization and defines a prognostic signature in glioblastoma

et al. 2018

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Despite post-operative radio-chemotherapy, glioblastoma systematically locally recurs. Tumors contacting the periventricular zone (PVZ) show earlier and more distant relapses than tumors not contacting the PVZ. Since glioblastoma stem-like cells (GSCs) have been proposed to play a major role in glioblastoma recurrence, we decided to test whether GSC migration properties could be different according to their anatomical location (PVZ+/PVZ–). For that purpose, we established paired cultures of GSCs from the cortical area (CT) and the PVZ of glioblastoma patient tumors. We demonstrated that PVZ GSCs possess higher migration and invasion capacities than CT GSCs. We highlighted specific transcriptomic profiles in PVZ versus CT populations and identified a down-regulation of the RhoGTPase, RND1 in PVZ GSCs compared to CT GSCs. Overexpression of RND1, dramatically inhibited PVZ GSC migration and conversely, downregulation of RND1 increased CT GSC migration. Additionally, transcriptomic analyses also revealed a down-regulation of RND1 in glioblastoma compared to normal brain. Using the glioblastoma TCGA database, low levels of RND1 were also shown to correlate with a decreased overall survival of patients. Finally, based on signaling pathways activated in patients with low levels of RND1, we identified an RND1low signature of six genes (MET, LAMC1, ITGA5, COL5A1, COL3A1, COL1A2) that is an independent prognostic factor in glioblastoma. These findings contribute to explain the shorter time to progression of patients with PVZ involvement and, point out genes that establish the RND1low signature as key targets genes to impede tumor relapse after treatment.

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“…Another retrospective study of 43 patients with glioblastoma [24] was conducted to identify SVZ related prognostic factors for survival and recurrence patterns. Results on multivariate analysis showed contact to SVZ, as well as reduced bSVZ radiation dose coverage (V20Gy <84%), might be independent poor prognostic factors for time to progression (7 months versus 5.2 months, p = 0.017).…”

Section: Evidence Supporting Improved Survival With Higher Svz and Pvmentioning

confidence: 99%

Prospective study to assess the survival outcomes of planned irradiation of ipsilateral subventricular and periventricular zones in glioblastoma

Valiyaveettil¹,

Malik²,

Akram³

et al. 2020

ecancer

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Purpose/objective(s): Retrospective evidence suggests that the irradiation of stem cells in the periventricular zone (PVZ), specifically the subventricular zone (SVZ), to higher doses may be associated with improved outcomes. Materials/methods: This was a prospective study, done from 2012 to 2017 in glioblastoma patients to assess the efficacy of planned irradiation of ipsilateral PVZ and SVZ on survival outcomes. The clinical target volume included the tumour bed with a 1.5-2 cm margin, perilesional oedema and was expanded to encompass the ipsilateral PVZ (5 mm lateral expansion adjacent to the ventricles, including the SVZ, which was a 5 mm expansion lateral to lateral ventricle). The ipsilateral PVZ was planned to receive a dose of ≥50 Gy. Results: 89 patients were recruited of which 74 patients were available for the analysis. Median age was 48 years. Mean doses to ipsilateral PVZ and SVZ were 56.2 and 55.1Gy, respectively. Median overall survival in the entire group was 13 months. There was no significant correlation between survival and doses to ipsilateral, contralateral, or bilateral PVZ and SVZ. Median survival was 16, 12 and 6 months for Eastern Cooperative Oncology Group (ECOG) PS 1, 2 and 3, respectively (p = 0.05). Conclusion: Planned irradiation of potential stem cell niches in the ipsilateral cerebral hemisphere did not result in improved survival as suggested by retrospective studies. Doses to contralateral or bilateral PVZ or SVZ also did not influence survival.

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Subventricular zones: new key targets for glioblastoma treatment

Cited by 37 publications

References 56 publications

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

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

RND1 regulates migration of human glioblastoma stem-like cells according to their anatomical localization and defines a prognostic signature in glioblastoma

Prospective study to assess the survival outcomes of planned irradiation of ipsilateral subventricular and periventricular zones in glioblastoma

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