Abstract
ObjectiveTo determine the relationship between survival and glioblastoma distance from the ventricular-subventricular neural stem cell niche (VSVZ).Methods502 pre-operative gadolinium-enhanced, T1-weighted MRIs with glioblastoma retrieved from an institutional dataset (n = 252) and The Cancer Imaging Atlas (n=250) were independently reviewed. The shortest distance from the tumor contrast enhancement to the nearest lateral ventricular wall, the location of the VSVZ, was measured (GBM-VSVZDist). The relationship of GBM-VSVZDist with the proportion of glioblastomas at each distance point and overall survival was explored with a Pearson’s correlation and Cox regression model, respectively, adjusting for the well-established glioblastoma prognosticators.Results244/502 glioblastomas had VSVZ contact. The proportion of non-VSVZ-contacting glioblastomas correlated inversely with GBM-VSVZDist (partial Pearson’s correlation adjusted for tumor volume R=-0.79, p=7.11x10-7). A fit of the Cox regression model adjusted for age at diagnosis, Karnofsky performance status score, post-operative treatment with temozolomide and/or radiotherapy, IDH1/2 mutation status, MGMT promoter methylation status, tumor volume, and extent of resection demonstrated a significantly decreased overall survival only when glioblastoma contacted the VSVZ. Overall survival did not correlate with GBM-VSVZDist.ConclusionsIn the two independent cohorts analyzed, glioblastomas at diagnosis were found in close proximity or in contact with the VSVZ with a proportion that decreased linearly with GBM-VSVZDist. Patient survival was only influenced by the presence or absence of a gadolinium-enhanced glioblastoma contact with the VSVZ. These results may guide analyses to test differential effectiveness of VSVZ radiation in VSVZ-contacting and non-contacting glioblastomas and/or inform patient selection criteria in clinical trials of glioblastoma radiation.
Highlights
The median survival of patients with glioblastoma is 16 months [1, 2]
The microenvironment is especially attractive to glioblastoma cells [11, 12], and factors released by the VSVZ can mediate resistance to radiation therapy in glioblastoma cells [13]
The number of non-VSVZcontacting glioblastomas correlated inversely with GBMVSVZDist (R=-0.85, p=3.8x10-9; Figure 2A). This correlation was partly confounded by the inverse correlation of tumor volume with GBM-VSVZDist (R=-0.44, p=2.2x10-16; Figure 2B); it was adjusted for the median tumor volume at each GBM-VSVZDist value and remained significant
Summary
Survival is even lower in those patients in whom the glioblastoma has invaded or contacted the ventricular-subventricular zone (VSVZ) at diagnosis [3, 4]. The microenvironment is especially attractive to glioblastoma cells [11, 12], and factors released by the VSVZ can mediate resistance to radiation therapy in glioblastoma cells [13]. Consistent with these reports, recurrence is earlier in those patients in whom the initial glioblastoma invaded or contacted the VSVZ [3, 4]
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