Magnetic resonance hypoxia imaging for radiation treatment guidance in glioblastoma multiforme - a diagnostic/prognostic clinical imaging study

Abstract Local recurrence in glioblastoma (GBM) patients is caused by the ability of tumour cells to develop treatment resistance mechanisms. Hypoxia, which is present in subregions of GBM tumours, is the leading cause of resistance to radiotherapy and is associated with worse clinical outcomes in GBM. Current standard of care treatment does not account for tumour hypoxia. The ability to image tumour hypoxia at various stages of treatment offers opportunities to personalise and improve treatment for GBM patients. Preoperative imaging of tumour hypoxia offers the opportunity for supramarginal resections in surgical planning beyond current neurosurgical standard of care guidelines. Imaging hypoxia prior to radiotherapy enables selective dose escalation strategies to radioresistant tumour regions, increasing the likelihood of local control. Identifying hypoxic tumour regions harbouring progression at follow up is key to intervening at an early stage of tumour recurrence and personalising therapy tailored to the tumour response to treatment. Imaging of tumour hypoxia in routine clinical practice is challenging, as it requires 18FMISO PET, which is not available in most clinical centres. In this clinical imaging study, we aim to investigate the role of oxygen enhanced (OE) and blood-oxygen level dependent (BOLD) MRI as imaging biomarkers of hypoxia in GBM. Aiming to recruit 20 GBM patients, this study involves the addition of OE/BOLD MRI and 18FMISO PET imaging at several timepoints during the course of treatment. The primary objective is to investigate the ability of OE/BOLD MRI to map tumour hypoxia on preoperative scans using 18FMISO PET as the ground truth. Secondary objectives include evaluating the role of hypoxia imaging biomarkers for dose-painting radiotherapy planning and treatment response assessment in GBM. Overall, by validating the role of MRI biomarkers of hypoxia we ought to provide a non-invasive and more accessible means to more effective, personalised treatment to GBM patients.