FUTURE-GB: Functional and ultrasound-guided resection of glioblastoma: assessing the use of additional imaging during surgery to improve outcomes for patients with glioblastoma brain tumours

INTERVENTION: Stage 1 (IDEAL IIB study) of the trial is observational only and all participants will receive all technologies during surgery. Stage 2 will be randomised. Randomisation will be via the web‐based service provided by the Oxford Clinical Trials Research Unit (OCTRU), using the method of minimisation. Participants will be randomised 1:1 to either: 1. Standard care surgery (neuronavigation based on preoperative imaging and intraoperative use of 5‐ALA)(Control arm) 2. Standard care surgery (neuronavigation based on preoperative imaging and intraoperative use of 5‐ALA) AND of DTI neuronavigation and NiUS (Intervention arm) At baseline all participants will undergo a routine preoperative neuronavigation MRI scan. Those participants randomised to the experimental arm, will also have a DTI scan (additional 5 minutes in the MRI). All participants will then undergo the planned resection of their tumour, with the additional technologies if they are in the experimental arm. Following surgery, participants in both arms have the same follow up schedule and undergo standard clinical care for a total of 24 months. CONDITION: Glioblastoma ; Cancer ; Glioblastoma PRIMARY OUTCOME: ; Stage 1:; Feasibility of using DTI and NiUS in addition to standard of care for neurosurgery assessed using:; 1. Operation length measured using patient records, analysed post‐operatively; 2. Successful use of the technology measured using operating surgeon theatre reports completed during surgery and analysed post‐operatively; 3. Tumour resection shown by pre and post‐op MRI scan; 4. Surgical complications measured using number of return visits to theatre, and other medical complications and analysed at discharge; ; Stage 2:; Deterioration Free Survival (Global Health Status) measured using a composite measure obtained from the QLQ‐C30 patient and proxy questionnaire at baseline, 5 days post‐op/discharge, 6 weeks post‐op, 3 month post‐op, then every 3 months subsequently up to 24 months post‐op, Progression‐Free Survival (PFS) and Overall Survival (OS) measured using patient records; INCLUSION CRITERIA: 1. Aged 18 ‐ 75 years 2. Neuro‐oncology Multi‐Disciplinary Team (MDT) decision that the imaging shows a primary GB tumour which is maximally resectable (attempted gross total resection of all enhancing tumour) 3. Patient is suitable for concomitant 6 weeks adjuvant radiotherapy and temozolamide (TMZ) chemotherapy or adjuvant TMZ at the time of MDT decision 4. Willing and able to give informed consent 5. Able to understand written English to enable completion of trial questionnaires 6. Able to provide a proxy who is willing to complete questionnaires as requested SECONDARY OUTCOME: ; Measured at baseline, 5 days post‐op/discharge, 6 weeks post‐op, 3 month post‐op, then every 3 months subsequently up to 24 months post‐op (unless otherwise mentioned):; 1. Physical functioning, social functioning measured using the QLQ‐C30; 2. Motor dysfunction and communication deficit measured using the QLQ‐BN20; 3. Time to deterioration measured using a composite measure obtained from the QLQ‐C30 patient and proxy questionnaire, progression‐free survival (PFS) and overall survival (OS) measured using patient records; 4. Progression Free Survival (PFS) measured as time from randomisation to radiological tumour progression on imaging; 5. Extent of tumour resection measured as % of pre‐operative tumour volume on postoperative contrast enhanced MRI at post‐op review; 6. Incidence of Surgical Complications measured using patient records; 7. Number of patients eligible for adjuvant treatment (for radiotherapy and/or chemotherapy) following surgery measured using patient records; 8. Functional Outcome measured by results from standardised assessments:; 8.1. Activity ability measured using WHO performance status; 8.2. Cognitive function measured using Montreal Cognitive Assessment (MOCA); 8.3. Performance in activities of daily living measured using the Barthel Index; 8.4. Muscle power measured using MRC grading of power in all 4 limbs; 9. Participant classification assessment of quality of life, measured by answers to QoL questions provided by the participant and their proxy; ; Stage 2 tertiary outcome measures:; 1. Location of nerve tracts measured using DTI imaging pre and post‐surgery; 2. Location of nerve tracts measured using intraoperative direct electrical stimulation or motor evoked potential changes during surgery; 3. Location of tumour boundary measured using intraoperative NiUS images; 4. Location of tumour boundary measured using post‐operative MRI scans; 5. Location of tumour boundary measured using intraoperative biopsy samples;