Brain tumours are the leading cause of cancer deaths in children, men under the age of 45 and women under the age of 25. Glioblastoma is the most common and most malignant primary tumour. The predominant treatment is surgical removal of the tumour followed by radiotherapy. Sadly the majority of patients given this treatment develop recurrent and progressive disease.

Better understanding of the invasive margin might improve outcomes by facilitating more complete surgical resection beyond the traditional contrast enhancing margins. Diffusion tensor MRI (DTI) is an imaging technique which may be able to predict the site of tumour recurrence. DTI has previously been shown to identify regions, which have been confirmed with biopsies, to be areas of invasive tumours and are present before progression is seen with an MRI.

The primary aim of this study is to qualify an imaging biomarker that can be applied at initial presentation, that can accurately predict the site of where glioblastomas will progress after treatment and allow personalisation of both radiotherapy and surgical targets.

This is a multicentre, prospective longitudinal observational cohort study in patients with high grade glioma, who have surgery planned to remove >90% of the tumour, and subsequent radical radiotherapy with concomitant tomozolomide. The purpose of this study is to establish a model using DTI that can accurately predict the site of where glioblastomas will progress after treatment. This study aims to validate the use of DTI as a biomarker across multiple centres to develop analysis methods that could be used in the future to personalise radiotherapy treatment volumes, and potentially surgical targets.

Patients will be given a DTI-MRI both prior to the operation and prior to radiotherapy. Clinical MRIs will take place according to standard guidelines. Whilst the study is open patients will participate in the study until death. Once a total of 70 patients from the first 90 have shown true progression patients will participate in the study for a minimum of 6 months from the beginning of radiotherapy.

This study will be conducted in 6-10 NHS centres, where 120 patients will be recruited, patients who are withdrawn will be replaced.

Inclusion Criteria:

• Have given written informed consent to participate
• Assessed by a neuroscience MDT to have a high grade glioma on imaging, OR if in the opinion of the CI, with guidance from the local PI that all relevant and appropriate members of a multidisciplinary team agree a high grade glioma diagnosis;
• Considered suitable for radical radiotherapy (60 Gy) with concomitant chemotherapy (Stupp Regime);
• WHO PS 0 or 1 (see Appendix 3);
• Age ≥16;
• Patient suitable for tumour resection where the treating neurosurgeon feels that >90% of the enhancing tumour will be resected;

Exclusion Criteria:

• Patients who are participating in trials involving investigational treatments
• Patients who are unsuitable for a contrast-enhanced MRI will be excluded. Such clinical problems include, but are not limited to:
• MR unsafe metallic implants;
• Claustrophobia;
• Allergy to gadolinium contrast agent;
• History of severe renal impairment.
• Patients unable to provide written informed consent
• PET sub-study only: Pregnant women

Male and female patients aged 16 and over with newly diagnosed glioblastomas