Stem cell niche irradiation in glioblastoma: providing a ray of hope?

Abstract

Glioblastomas are organized hierarchically with a small number of glioblastoma stem cells that have unique self-renewal capacity and multilineage potency. The subventricular zone (SVZ) constitutes the largest neural stem cell niche in the adult human brain; it may also act as a reservoir of glioblastoma stem cells that can initiate, promote or repopulate a tumor. Incidental irradiation of SVZ has been shown to potentially influence outcomes suggesting that aggressively targeting the stem cell niche may offer a ray of hope in glioblastoma. The following review provides a summary of the experimental evidence supporting the origin and location of the putative glioblastoma stem cell in the SVZ, and offers a critical appraisal of the growing body of clinical evidence correlating SVZ dosimetry with outcomes in glioblastoma.

Keywords: glioblastoma; invasion; migration; radiotherapy; stem cell niche; subventricular zone.

Figure 1.. Migratory patterns in glioblastoma.

(A) Axial MRI with left subventricular zone (in pink) showing the various embryonal neuronal migration pathways. (B) Coronal and (C) sagittal sections showing ‘ventricle-directed’ migration of cortical tumors (in yellow) and ‘tangential, multi-polar’ migration of tumors (in green) arising in close proximity to the subventricular zone.

Figure 2.. 3D dose distribution.

Dose-wash in (A) axial, (B) coronal and (C) sagittal sections with (D) 3D dose reconstruction on a planning CT scan. Note that coverage of the planning target volume (in red) by 95% isodose (in green) results in high-dose irradiation of the ipsilateral SVZ (in blue) while sparing most of the contralateral SVZ (in brown).