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

Ermiş, Ekin; Althaus, Alexander; Blatti, Marcela; Uysal, Emre; Leiser, Dominic; Norouzi, Shokoufe; Riggenbach, Elena; Hemmatazad, Hossein; Ahmadli, Uzeyir; Wagner, Franca (2023). Therapy Resistance of Glioblastoma in Relation to the Subventricular Zone: What Is the Role of Radiotherapy? Cancers, 15(6) MDPI AG 10.3390/cancers15061677

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Radiology, Neuroradiology and Nuclear Medicine (DRNN) > Institute of Diagnostic and Interventional Neuroradiology
04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Radiation Oncology

UniBE Contributor:

Ermis, Ekin, Althaus, Alexander Maria Georg, Blatti, Marcela Judith, Riggenbach, Elena, Hemmatazad, Hossein, Ahmadli, Uzeyir, Wagner, Franca

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2072-6694

Publisher:

MDPI AG

Language:

English

Submitter:

Pubmed Import

Date Deposited:

30 Mar 2023 11:28

Last Modified:

31 Mar 2023 07:59

Publisher DOI:

10.3390/cancers15061677

PubMed ID:

36980563

Uncontrolled Keywords:

glioblastoma microenvironment radiotherapy subventricular zone therapeutic resistance

BORIS DOI:

10.48350/181080

URI:

https://boris.unibe.ch/id/eprint/181080

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