Influence of glioblastoma contact with the lateral ventricle on survival: a meta-analysis

Abstract

The ventricular-subventricular zone (V-SVZ), which lies in the walls of the lateral ventricles (LV), is the largest neurogenic niche within the adult brain. Whether radiographic contact with the LV influences survival in glioblastoma (GBM) patients remains unclear. We assimilated and analyzed published data comparing survival in GBM patients with (LV+GBM) and without (LV−GBM) radiographic LV contact. PubMed, EMBASE, and Cochrane electronic databases were searched. Fifteen studies with survival data on LV+GBM and LV−GBM patients were identified. Their Kaplan–Meier survival curves were digitized and pooled for generation of median overall (OS) and progression free (PFS) survivals and log-rank hazard ratios (HRs). The log-rank and reported multivariate HRs after accounting for the common predictors of GBM survival were analyzed separately by meta-analyses. The calculated median survivals (months) from pooled data were 12.95 and 16.58 (OS), and 4.54 and 6.25 (PFS) for LV+GBMs and LV−GBMs, respectively, with an overall log-rank HRs of 1.335 [1.204–1.513] (OS) and 1.387 [1.225–1.602] (PFS). Meta-analysis of log-rank HRs resulted in summary HRs of 1.58 [1.35–1.85] (OS, 10 studies) and 1.41 [1.22–1.64] (PFS, 5 studies). Meta-analysis of multivariate HRs resulted in summary HRs of 1.35 [1.14–1.58] (OS, 6 studies) and 1.64 [0.88–3.05] (PFS, 3 studies). Patients with GBM contacting the LV have lower survival. This effect may be independent of the common predictors of GBM survival, suggesting a clinical influence of V-SVZ contact on GBM biology.

Neural Precursor-Derived Pleiotrophin Mediates Subventricular Zone Invasion by Glioma

“…The SVZ is a site of frequent spread in HGG, and glioma spread to the SVZ is associated with decreased survival (Chaichana et al, 2008; Jafri et al, 2013; Mistry et al, 2017a, 2017b) and increased tumor recurrence (Adeberg et al, 2014; Chen et al, 2015). Notably, decreased survival and increased early recurrence in adult GBM are associated specifically with glioma contact of the lateral ventricle SVZ (Mistry et al, 2017b), for reasons that have yet to be fully elucidated.…”

“…The lateral ventricle subventricular zone (SVZ) stem cell niche is thought to be a tumor reservoir for a range of HGGs including adult glioblastoma (GBM). Glioma contact of neural stem cell niches, particularly the SVZ, has been closely associated with decreased survival (Chaichana et al, 2008; Jafri et al, 2013; Mistry et al, 2017a, 2017b) and increased tumor recurrence (Adeberg et al, 2014; Chen et al, 2015). Diffuse intrinsic pontine glioma (DIPG; recently re-classified as diffuse midline glioma, H3K27M mutant (Louis et al, 2016)) is the most common HGG of childhood and the leading cause of pediatric brain tumor-related death, with a median survival of only 9 months and a 5-year survival of less than 1% (Donaldson et al, 2006).…”

Decreased survival in glioblastomas is specific to contact with the ventricular-subventricular zone, not subgranular zone or corpus callosum

“…Patients with GBMs spreading along the CC have been shown to have decreased survival, [8–11] although the basis of this effect remains unclear. While some studies suggest a greater malignant potential of GBMs with VSVZ contact (VSVZ+ GBMs), the majority of these studies were conducted on small cohorts (<100 total patients) [12]. Further, the cumulative clinical data is limited by heterogeneous accounting of common, well-known survival confounders and other clinical variables such as extent of resection and tumor volume [12–18].…”

“…While some studies suggest a greater malignant potential of GBMs with VSVZ contact (VSVZ+ GBMs), the majority of these studies were conducted on small cohorts (<100 total patients) [12]. Further, the cumulative clinical data is limited by heterogeneous accounting of common, well-known survival confounders and other clinical variables such as extent of resection and tumor volume [12–18]. On the other hand, the clinical impact of GBM contact with SGZ is relatively unexplored.…”

The Crossroads of Neural Stem Cell Development and Tumorigenesis

“…BTSCs possess properties that are highly characteristic of NSCs such as the ability to self-renew, divide, and differentiate into distinct cell lineages. Indeed, tumor invasiveness, recurrence, or overall poor survival of patients with glioblastoma multiforme (GBM) can be predicted based on the proximity of the tumors to the SVZ (Jafri et al, 2013; Lim et al, 2007), or whether tumors are in contact with the lateral ventricle (Mistry et al, 2016). Similar to the neurogenic niche, a characteristic signature of brain tumors are their highly vascular nature (Calabrese et al, 2007; Wesseling et al, 1993) and increased vascular density has long been considered a prognostic indicator of malignant tumor progression (Calabrese et al, 2007; Leon et al, 1996) (Figure 2).…”