Can irradiation of potential cancer stem-cell niche in the subventricular zone influence survival in patients with newly diagnosed glioblastoma?

Abstract

Glioblastoma progenitor or stem cells residing in the stem-cell niche in the subventricular zones (SVZ) can initiate or promote tumorigenesis. They can also migrate throughout the brain, resulting in disease progression. Irradiation of potential cancer stem-cell niche in the SVZ may influence survival. To analyze radiotherapy dose-volume parameters to the SVZ that correlate with survival in adequately treated patients with newly diagnosed glioblastoma, 40 adults with histopathologically proven supratentorial glioblastoma with available baseline imaging treated with postoperative conventionally fractionated focal conformal radiotherapy plus chemotherapy, available radiotherapy planning dataset, and documented event of progression or death or minimum 6-month follow-up were included in this retrospective study. Dose-volume parameters to the SVZ were extracted from treatment planning system and analyzed in relation to survival outcomes. Mean ipsilateral and contralateral SVZ volumes were 5.6 and 6.4 cc, respectively. With median follow-up of 15 months (interquartile range 12-18 months), median [95 % confidence interval (CI)] progression-free survival (PFS) and overall survival (OAS) was 11 months (95 % CI 8.9-13.0 months) and 17 months (95 % CI 11.6-22.4 months), respectively. Older age (>50 years), poor recursive partitioning analysis (RPA) class, and higher than median of mean contralateral SVZ dose were associated with significantly worse PFS and OAS. Multivariate analysis identified RPA class, Karnofsky performance status, and mean ipsilateral SVZ dose as independent predictors of survival. Increasing mean dose to the ipsilateral SVZ was associated with significantly improved OAS. Irradiation of potential cancer stem-cell niche influences survival outcomes in patients with newly diagnosed glioblastoma.

The SVZ and Its Relationship to Stem Cell Based Neuro-oncogenesis

“…In a pooled analysis of 173 GBM patients from two academic centers, these results were confi rmed as high radiation therapy doses to the ipsilateral SVZ led to significantly longer progression free survival. An analysis of 40 GBM patients found statically signifi cant improved overall survival in patients who received high dose of ipsilateral SVZ radiation [ 43 ]. In a recent investigation of 100 GBM patients-50 long term survivors (>3 years) and 50 short term survivors (<1 year), SVZ tumor contact was found to be a signifi cant predictor of prolonged survival, in addition to age and total resection status [ 40 ].…”

Subventricular Zone Involvement Characterized by Diffusion Tensor Imaging in Glioblastoma

“…[15][16][17] Ventricle masks were created in GeoS (Microsoft Corporation, Redmond, Washington, USA) from the preoperative T1-weighted post-contrast images. 18 Non-enhancing FLAIR maps were generated from coregistered T2-FLAIR sequences in 3D slicer (http://www.slicer.org).…”

La niche des cellules souches tumorales dans le glioblastome : des aspects fondamentaux au ciblage thérapeutique

“…Un autre aspect, après le ciblage médicamenteux, est l'irradiation spécifique des niches de CSG permise par une meilleure définition des volumes anatomiques pouvant se rapporter à la niche périvasculaire. Une étude rétrospective de Gupta et al sur 40 patients atteints de GB démontre que la radiothérapie ciblant les zones périventriculaires homolatérales à la tumeur augmente la survie globale [54]. Cette étude, avec les limites inhérentes au caractère rétrospectif et au faible nombre de patients inclus, met en évidence l'importance de l'amélioration des techniques d'imagerie dans la définition de volumes anatomiques afin de cibler la niche.…”