Survival impact of incidental subventricular zone irradiation in IDH-wildtype glioblastoma

Abstract

Background and purpose

The subventricular zone (SVZ) is an important niche for neural stem cells but probably also for brain tumor propagating cells, including the glioblastoma stem cell. The SVZ may become a target for radiation therapy in glioblastoma patients. However, reports studying the effect of irradiation of the SVZ on glioblastoma patient survival show conflicting results. We studied the correlation between incidental SVZ radiation dose and survival in a cohort of isocitrate dehydrogenase-wildtype (IDHwt) glioblastoma patients with inclusion of important survival prognosticators.

Patients and methods

In this retrospective analysis, only adult patients with supratentorial IDHwt glioblastoma were included who were treated with temozolomide-based chemoradiotherapy after surgery. The SVZ was contoured on the radiotherapy planning imaging. Cox proportional regression overall survival (OS) analysis was used to study the correlation between SVZ dose and survival. Age, Karnofsky Performance Score, extent of resection and O⁶-methylguanine-methyl-DNA-transferase gene promoter (MGMTp) methylation were used as covariates in multivariate analysis.

Results

In total, 137 patients were included. Median OS was 13.3 months. The MGMTp methylation was present in 40% of cases. Ipsilateral SVZ (iSVZ) mean dose was 44.4 Gy and 27.2 Gy for the contralateral SVZ (cSVZ). Univariate survival analysis showed an inverse relationship between cSVZ mean dose and OS (HR 1.029 (1.003–1.057); p= .032). However, there was no correlation between cSVZ mean dose and OS in multivariate analysis. iSVZ dose did not correlate with survival.

Conclusion

In this cohort of 137 IDHwt glioblastoma patients, iSVZ did not correlate with OS. Higher cSVZ dose was inversely correlated with OS in univariate survival analysis but lost its significance in multivariate analysis, including MGMTp-methylation. Hence, the correlation between SVZ radiation and glioblastoma patient survival remains unclear. Carefully designed prospective studies are needed to provide unequivocal results on this controversial topic.

Keywords:

• Glioblastoma
• IDH-wildtype
• subventricular zone
• radiation therapy survival
• MGMT-methylation

Acknowledgements

The authors gratefully acknowledge the help of Prof. em. Dr. M. Mareel with the study. We are in debt to the radiophysicists of AZ Delta and Ghent University Hospital for their help in retrieving and restoring the dosimetric data. We would like to specifically acknowledge the efforts made by F. Vanhoutte, PhD, H. Vanhauwaert, T. Vercauteren, and W. De Gersem, PhD.

Ethics approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This study was approved by the ethics committee of each hospital (Belgian registration number B670201730765; UZG 2016/1594; AZD 17004).

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

Research data are available on request.

Additional information

Funding

This work was financially supported by grants from the following nonprofit organizations: Ghent University Hospital, Centre for Oncology; Lux Luka Foundation and Fonds Arne Lannoy AKA Zorro.