Investigating the effect of radiotherapy to the SubVentricular Zone (SVZ) in high-grade glioma patients

  • Thomas Hague

Student thesis: Unknown

Abstract

Glioblastoma multiforme (GBM) is the most aggressive type of malignant brain tumour. Despite treatments including surgery, chemotherapy and radiotherapy, GBM recurrence rates are high and patient prognosis remains poor. The SubVentricular Zone (SVZ) may have a role in tumour recurrence as it is theorised to provide a sanctuary or ‘niche’ for migrating glioma stem cells, whose escape and survival from therapeutic intervention are thought to drive future disease relapse. On this basis, inclusion of the SVZ within the radiotherapy target volume has been proposed by several authors, however there is conflicting current evidence on the benefits of SVZ irradiation and the subject remains controversial. Amidst calls for randomised prospective clinical trials on SVZ radiotherapy, the potential role of the SVZ in GBM still requires some clarification. This thesis describes the investigation into the effect of radiotherapy to the SVZ for patients in the author’s centre. A retrospective study of 57 patients examined the prognostic impact on patient Overall Survival of the mean incidental dose delivered to the SVZ during radiotherapy, analysed alongside other prognostic covariables such as age and tumour genetic factors. SVZ dose appeared to have no significant impact on survival as only increasing patient age, unmethylated O6-methylguanine-DNA-methyltransferase (MGMT) gene status and absence of chemotherapy proved to be detrimental to Overall Survival in this cohort. A subsequent radiological study further categorised patients using a novel classification methodology based on tumour proximity to and invasion of the SVZ, finding also that this had no significant impact on Overall Survival. This study also investigated inter-observer variability when contouring the SVZ and the considerable discordance seen in the results highlights the importance of clear delineation protocols, though reported dosimetric findings were not affected. Though the results of this investigation are currently inconclusive on the potential role of SVZ radiotherapy in improving survival in GBM, a potential area of renewed research focus has been identified through the novel classification methodology introduced in this work. Future studies should perhaps aim to investigate the potential role of radiotherapy in improving survival for a subset of patients with SVZ-invasive tumours, where complete surgical resection is often not possible.
Date of Award1 Aug 2023
Original languageEnglish
Awarding Institution
  • The University of Manchester
SupervisorKaren Kirkby (Supervisor)

Keywords

  • subventricular zone
  • brain tumour
  • SVZ
  • GBM
  • radiotherapy
  • glioblastoma multiforme

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