Subventricular zone contacting glioblastoma: tumor size, molecular biological factors and patient survival

Acta Oncol. 2020 Dec;59(12):1474-1479. doi: 10.1080/0284186X.2020.1794032. Epub 2020 Jul 16.

Abstract

Background: Several studies show that subventricular zone (SVZ) contact of glioblastoma at diagnosis is a negative prognosticator of survival. In this report, we study glioblastoma patient survival, molecular biological and MRI-based volumetric findings according to SVZ contact.

Patients and methods: We conducted a retrospective study of adult patients diagnosed with supratentorial glioblastoma and uniformly treated with temozolomide-based chemoradiotherapy after surgery. The patient cohort was dichotomized according to tumor contact with the SVZ at diagnosis as determined on preoperative MR imaging. Tumor volume was measured using semi-automated segmentation technique. MGMT-gene promoter methylation and IDH mutation status were determined on stored tumor tissue. Kaplan-Meier survival curves were constructed. Cox regression analysis was used to adjust for known confounding factors of glioblastoma patient survival.

Results: A total of 214 patients were included in the study of whom 68% belonged to the SVZpos group. Median tumor volume was significantly larger in the SVZpos group (33,8 mL vs 15,6 mL; p < .001). MGMT-unmethylated glioblastoma was more frequent in the SVZpos group (61.4% vs 44.9%; p = .028). The overall survival and progression-free survival were 12.2 months and 5.9 months for the SVZpos patient group but 16.9 months and 10.3 months for the SVZneg group (log-rank p = .016 and .007 respectively). In multivariate Cox survival analysis, SVZ contact proved a negative prognostic parameter, independent from age, KPS, extent of resection, MGMT-methylation and IDH mutation status.

Conclusions: This study confirms SVZ contact at diagnosis as an independent negative prognostic factor for glioblastoma patient survival. SVZpos glioblastoma had larger tumor size and a larger proportion of unmethylated tumors than SVZneg glioblastoma. Further research is needed to establish whether the observed differences are solely explained by a different molecular profile of SVZpos glioblastoma or by interaction of glioblastoma with the unique SVZ microenvironment.

MeSH terms

  • Adult
  • Antineoplastic Agents, Alkylating / therapeutic use
  • Biological Factors / therapeutic use
  • Brain Neoplasms* / drug therapy
  • Brain Neoplasms* / therapy
  • DNA Modification Methylases / genetics
  • DNA Repair Enzymes / genetics
  • Glioblastoma* / drug therapy
  • Glioblastoma* / therapy
  • Humans
  • Lateral Ventricles
  • Prognosis
  • Retrospective Studies
  • Tumor Microenvironment

Substances

  • Antineoplastic Agents, Alkylating
  • Biological Factors
  • DNA Modification Methylases
  • DNA Repair Enzymes