Randomized Controlled Trial

. 2022 Nov 15;12(11):e064823.

doi: 10.1136/bmjopen-2022-064823.

FUTURE-GB: functional and ultrasound-guided resection of glioblastoma - a two-stage randomised control trial

Puneet Plaha^{1

2}, Sophie Camp³, Jonathan Cook⁴, Peter McCulloch², Natalie Voets⁵, Ruichong Ma^{6

2}, Martin J B Taphoorn^{7

8}, Linda Dirven⁷, Matthew Grech-Sollars^{9

10}, Colin Watts^{11

12}, Helen Bulbeck¹³, Michael D Jenkinson^{14

15}, Matthew Williams¹⁶, Adrian Lim^{17

18}, Luke Dixon¹⁹, Stephen John Price²⁰, Keyoumars Ashkan²¹, Vasileios Apostolopoulos⁶, Vicki S Barber⁴, Amy Taylor²; FUTURE-GB collaborators; Dipankar Nandi^{3

17}

Collaborators, Affiliations

Collaborators

Affiliations

¹ Department of Neursurgery, Oxford University Hospitals NHS Foundation Trust, Oxford, UK puneet.plaha@ouh.nhs.uk.
² Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK.
³ Neurosurgery, Imperial College Healthcare NHS Trust, London, UK.
⁴ Oxford Clinical Trials Research Unit & Surgical Intervention Trials Unit, University of Oxford Nuffield Department of Orthopaedics Rheumatology and Musculoskeletal Sciences, Oxford, Oxfordshire, UK.
⁵ Nuffield Department of Clinical Neurosciences, Oxford University, Oxford, Oxfordshire, UK.
⁶ Department of Neursurgery, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
⁷ Department of Neurology, Leiden University Medical Center, Leiden, Zuid-Holland, The Netherlands.
⁸ Department of Neurology, Haaglanden Medical Center Bronovo, Den Haag, Zuid-Holland, The Netherlands.
⁹ Department of Computer Sciences, UCL, London, UK.
¹⁰ Lysholm Department of Neuroradiology, National Hospital for Neurology and Neurosurgery, London, UK.
¹¹ Institute of Cancer and Genomic Studies, University of Birmingham, Birmingham, UK.
¹² Department of Neurosurgery, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
¹³ Brainstrust, Cowes, UK.
¹⁴ Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, Merseyside, UK.
¹⁵ Department of Neurosurgery, Walton Centre for Neurology and Neurosurgery, Liverpool, UK.
¹⁶ Department of Clinical Oncology, Imperial College Healthcare NHS Trust, London, UK.
¹⁷ Department of Surgery and Cancer, Imperial College London, London, UK.
¹⁸ Department of Imaging, Imperial College Healthcare NHS Trust, London, UK.
¹⁹ Neuroradiology, Imperial College Healthcare NHS Trust, London, UK.
²⁰ Neurosurgery Division, Department of Clinical Neurosciences, Cambridge University, Cambridge, UK.
²¹ Department of Neurosurgery, King's College Hospital, London, UK.

PMID: 36379652
PMCID: PMC9668053
DOI: 10.1136/bmjopen-2022-064823

Randomized Controlled Trial

FUTURE-GB: functional and ultrasound-guided resection of glioblastoma - a two-stage randomised control trial

Puneet Plaha et al. BMJ Open. 2022.

. 2022 Nov 15;12(11):e064823.

doi: 10.1136/bmjopen-2022-064823.

Authors

Collaborators

Affiliations

¹ Department of Neursurgery, Oxford University Hospitals NHS Foundation Trust, Oxford, UK puneet.plaha@ouh.nhs.uk.
² Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK.
³ Neurosurgery, Imperial College Healthcare NHS Trust, London, UK.
⁴ Oxford Clinical Trials Research Unit & Surgical Intervention Trials Unit, University of Oxford Nuffield Department of Orthopaedics Rheumatology and Musculoskeletal Sciences, Oxford, Oxfordshire, UK.
⁵ Nuffield Department of Clinical Neurosciences, Oxford University, Oxford, Oxfordshire, UK.
⁶ Department of Neursurgery, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
⁷ Department of Neurology, Leiden University Medical Center, Leiden, Zuid-Holland, The Netherlands.
⁸ Department of Neurology, Haaglanden Medical Center Bronovo, Den Haag, Zuid-Holland, The Netherlands.
⁹ Department of Computer Sciences, UCL, London, UK.
¹⁰ Lysholm Department of Neuroradiology, National Hospital for Neurology and Neurosurgery, London, UK.
¹¹ Institute of Cancer and Genomic Studies, University of Birmingham, Birmingham, UK.
¹² Department of Neurosurgery, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
¹³ Brainstrust, Cowes, UK.
¹⁴ Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, Merseyside, UK.
¹⁵ Department of Neurosurgery, Walton Centre for Neurology and Neurosurgery, Liverpool, UK.
¹⁶ Department of Clinical Oncology, Imperial College Healthcare NHS Trust, London, UK.
¹⁷ Department of Surgery and Cancer, Imperial College London, London, UK.
¹⁸ Department of Imaging, Imperial College Healthcare NHS Trust, London, UK.
¹⁹ Neuroradiology, Imperial College Healthcare NHS Trust, London, UK.
²⁰ Neurosurgery Division, Department of Clinical Neurosciences, Cambridge University, Cambridge, UK.
²¹ Department of Neurosurgery, King's College Hospital, London, UK.

PMID: 36379652
PMCID: PMC9668053
DOI: 10.1136/bmjopen-2022-064823

Abstract

Introduction: Surgery remains the mainstay for treatment of primary glioblastoma, followed by radiotherapy and chemotherapy. Current standard of care during surgery involves the intraoperative use of image-guidance and 5-aminolevulinic acid (5-ALA). There are multiple other surgical adjuncts available to the neuro-oncology surgeon. However, access to, and usage of these varies widely in UK practice, with limited evidence of their use. The aim of this trial is to investigate whether the addition of diffusion tensor imaging (DTI) and intraoperative ultrasound (iUS) to the standard of care surgery (intraoperative neuronavigation and 5-ALA) impacts on deterioration free survival (DFS).

Methods and analysis: This is a two-stage, randomised control trial (RCT) consisting of an initial non-randomised cohort study based on the principles of the IDEAL (Idea, Development, Exploration, Assessment and Long-term follow-up) stage-IIb format, followed by a statistically powered randomised trial comparing the addition of DTI and iUS to the standard of care surgery. A total of 357 patients will be recruited for the RCT. The primary outcome is DFS, defined as the time to either 10-point deterioration in health-related quality of life scores from baseline, without subsequent reversal, progressive disease or death.

Ethics and dissemination: The trial was registered in the Integrated Research Application System (Ref: 264482) and approved by a UK research and ethics committee (Ref: 20/LO/0840). Results will be published in a peer-reviewed journal. Further dissemination to participants, patient groups and the wider medical community will use a range of approaches to maximise impact.

Trial registration number: ISRCTN38834571.

Keywords: Clinical trials; Neurosurgery; SURGERY.

PubMed Disclaimer

Conflict of interest statement

Competing interests: None declared.

Figures

**Figure 1**
Trial flowchart. DTI, diffusion tensor imaging; intraop, intraoperative; iUS, intraoperative ultrasound; HRQoL, health-related quality of life; 5-ALA, 5-aminolevulinic acid; IDEAL, Idea, Development, Exploration, Assessment and Long-term follow-up; MOCA, Montreal Cognitive Assessment; MRC, Medical Research Council

See this image and copyright information in PMC

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FUTURE-GB: functional and ultrasound-guided resection of glioblastoma - a two-stage randomised control trial

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FUTURE-GB: functional and ultrasound-guided resection of glioblastoma - a two-stage randomised control trial

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