Therapy Resistance of Glioblastoma in Relation to the Subventricular Zone: What Is the Role of Radiotherapy?

SIMPLE SUMMARY: Glioblastoma is a highly aggressive form of brain tumors characterized by rapid growth. The subventricular zone (SVZ) is an important region in the brain for processes such as neurogenesis, learning and memory, and brain repair after injury. Some studies have shown that glioblastoma stem cells can originate from the SVZ and have been reported to be responsible for the recurrent nature of the disease and for the failure of conventional treatments. Irradiation of these regions could improve patient outcomes. In our study, we investigated the impact of targeting the ipsilateral SVZ and preserving the contralateral SVZ during radiation treatment on patient outcomes. ABSTRACT: Glioblastoma is a highly heterogeneous primary malignant brain tumor with marked inter-/intratumoral diversity and a poor prognosis. It may contain a population of neural stem cells (NSC) and glioblastoma stem cells that have the capacity for migration, self-renewal and differentiation. While both may contribute to resistance to therapy, NSCs may also play a role in brain tissue repair. The subventricular zone (SVZ) is the main reservoir of NSCs. This study investigated the impact of bilateral SVZ radiation doses on patient outcomes. We included 147 patients. SVZs were delineated and the dose administered was extracted from dose–volume histograms. Tumors were classified based on their spatial relationship to the SVZ. The dose and outcome correlations were analyzed using the Kaplan–Meier and Cox proportional hazards regression methods. Median progression-free survival (PFS) was 7 months (range: 4–11 months) and median overall survival (OS) was 14 months (range: 9–23 months). Patients with an ipsilateral SVZ who received ≥50 Gy showed significantly better PFS (8 versus 6 months; p < 0.001) and OS (16 versus 11 months; p < 0.001). Furthermore, lower doses (<32 Gy) to the contralateral SVZ were associated with improved PFS (8 versus 6 months; p = 0.030) and OS (15 versus 11 months; p = 0.001). Targeting the potential tumorigenic cells in the ipsilateral SVZ while sparing contralateral NSCs correlated with an improved outcome. Further studies should address the optimization of dose distribution with modern radiotherapy techniques for the areas surrounding infiltrated and healthy SVZs.