Glioblastoma is the commonest primary malignant brain tumour in adults with an incidence of 4-7 per 100,000 population in England. Its outcome is particularly poor with a median survival of just 15 months and there is an urgent need for new treatment strategies. The current treatment pathway comprises maximal safe resection and postoperative chemoradiotherapy, which ultimately fails to prevent tumour progression. The latter can occur rapidly, even in the time interval between surgery and postoperative treatment, referred to as Rapid Early Progression (REP). Other limitations of the current pathway include the fact that unresectable, diffusely infiltrative tumour cells remain untreated for several weeks post-diagnosis, and that adjuvant therapies are delivered to a relatively hypoxic postoperative tumour bed. There is strong rationale to explore intensified upfront treatments for glioblastoma, such as at the preoperative time point, which could overcome these limitations. Preoperative treatments have not been explored due to the potential difficulties of establishing patient diagnosis and perceived disruption to neurosurgical workflow. Radiotherapy is a widely accessible cornerstone of treatment and could be delivered preoperatively. This thesis explores preoperative radiotherapy for newly-diagnosed glioblastoma, from rationale, to setup of a novel clinical trial and preliminary results. Rationale is explored by investigating REP. A meta-analysis of the literature is presented that assimilates current knowledge on REP, followed by a local case- control study that characterises this phenomenon through comparison of REP cases to propensity-score matched controls. The second part of this thesis describes the setup of a novel phase I trial that aims to evaluate the safety and feasibility of preoperative radiotherapy for newly-diagnosed glioblastoma - POBIG (PreOperative Brain Irradiation in Glioblastoma). Clinical outcomes and diffusion/perfusion-based magnetic resonance imaging data are presented from the first three patients treated with 8 Gy preoperative radiotherapy. This thesis presents data that represents a significant milestone in the treatment of glioblastoma patients and provides a framework for POBIG and future preoperative interventional studies.
- Neoadjuvant
- Radiotherapy
- Preoperative
- Glioblastoma
Preoperative Radiotherapy for Glioblastoma
Waqar, M. (Author). 31 Dec 2024
Student thesis: Phd