Thomas C Booth1,2, Gerard Thompson3, Helen Bulbeck4, Florien Boele5,6, Craig Buckley7, Jorge Cardoso1, Liane Dos Santos Canas1, David Jenkinson8, Keyoumars Ashkan9, Jack Kreindler10, Nicky Huskens11, Aysha Luis1,12, Catherine McBain13, Samantha J Mills14, Marc Modat1, Nick Morley15, Caroline Murphy16, Sebastian Ourselin1, Mark Pennington17, James Powell18, David Summers19, Adam D Waldman3, Colin Watts20,21, Matthew Williams22, Robin Grant3, Michael D Jenkinson23,24. 1. School of Biomedical Engineering & Imaging Sciences, King's College London, London, United Kingdom. 2. Department of Neuroradiology, King's College Hospital NHS Foundation Trust, London, United Kingdom. 3. Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom. 4. Brainstrust, Cowes, United Kingdom. 5. Leeds Institute of Medical Research at St James's, St James's University Hospital, Leeds, United Kingdom. 6. Faculty of Medicine and Health, Leeds Institute of Health Sciences, University of Leeds, Leeds, United Kingdom. 7. Siemens Healthineers, Frimley, United Kingdom. 8. The Brain Tumour Charity, Fleet, United Kingdom. 9. Department of Neurosurgery, King's College Hospital NHS Foundation Trust, London, United Kingdom. 10. ACT for Cancer, London, United Kingdom. 11. The Tessa Jowell Brain Cancer Mission, London, United Kingdom. 12. Lysholm Department of Neuroradiology, National Hospital for Neurology and Neurosurgery, London, United Kingdom. 13. Department of Oncology, Christie Hospital NHS Foundation Trust, Manchester, United Kingdom. 14. Department of Neuroradiology, The Walton Centre NHS Foundation Trust, Liverpool, United Kingdom. 15. Department of Radiology, Wales Research and Diagnostic PET Imaging Centre, Cardiff University School of Medicine, Cardiff, United Kingdom. 16. King's College Trials Unit, King's College London, London, United Kingdom. 17. King's Health Economics, King's College London, London, United Kingdom. 18. Department of Oncology, Velindre Cancer Centre, Cardiff, United Kingdom. 19. Department of Neuroradiology, Western General Hospital, Edinburgh, United Kingdom. 20. Birmingham Brain Cancer Program, University of Birmingham, Birmingham, United Kingdom. 21. University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom. 22. Department of Neuro-oncology, Imperial College Healthcare NHS Trust, London, United Kingdom. 23. Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom. 24. Department of Neurosurgery, The Walton Centre NHS Foundation Trust, Liverpool, United Kingdom.
Abstract
OBJECTIV E: To summarise current evidence for the utility of interval imaging in monitoring disease in adult brain tumours, and to develop a position for future evidence gathering while incorporating the application of data science and health economics. METHODS: Experts in 'interval imaging' (imaging at pre-planned time-points to assess tumour status); data science; health economics, trial management of adult brain tumours, and patient representatives convened in London, UK. The current evidence on the use of interval imaging for monitoring brain tumours was reviewed. To improve the evidence that interval imaging has a role in disease management, we discussed specific themes of data science, health economics, statistical considerations, patient and carer perspectives, and multi-centre study design. Suggestions for future studies aimed at filling knowledge gaps were discussed. RESULTS: Meningioma and glioma were identified as priorities for interval imaging utility analysis. The "monitoring biomarkers" most commonly used in adult brain tumour patients were standard structural MRI features. Interval imaging was commonly scheduled to provide reported imaging prior to planned, regular clinic visits. There is limited evidence relating interval imaging in the absence of clinical deterioration to management change that alters morbidity, mortality, quality of life, or resource use. Progression-free survival is confounded as an outcome measure when using structural MRI in glioma. Uncertainty from imaging causes distress for some patients and their caregivers, while for others it provides an important indicator of disease activity. Any study design that changes imaging regimens should consider the potential for influencing current or planned therapeutic trials, ensure that opportunity costs are measured, and capture indirect benefits and added value. CONCLUSION: Evidence for the value, and therefore utility, of regular interval imaging is currently lacking. Ongoing collaborative efforts will improve trial design and generate the evidence to optimise monitoring imaging biomarkers in standard of care brain tumour management.
OBJECTIV E: To summarise current evidence for the utility of interval imaging in monitoring disease in adult brain tumours, and to develop a position for future evidence gathering while incorporating the application of data science and health economics. METHODS: Experts in 'interval imaging' (imaging at pre-planned time-points to assess tumour status); data science; health economics, trial management of adult brain tumours, and patient representatives convened in London, UK. The current evidence on the use of interval imaging for monitoring brain tumours was reviewed. To improve the evidence that interval imaging has a role in disease management, we discussed specific themes of data science, health economics, statistical considerations, patient and carer perspectives, and multi-centre study design. Suggestions for future studies aimed at filling knowledge gaps were discussed. RESULTS: Meningioma and glioma were identified as priorities for interval imaging utility analysis. The "monitoring biomarkers" most commonly used in adult brain tumour patients were standard structural MRI features. Interval imaging was commonly scheduled to provide reported imaging prior to planned, regular clinic visits. There is limited evidence relating interval imaging in the absence of clinical deterioration to management change that alters morbidity, mortality, quality of life, or resource use. Progression-free survival is confounded as an outcome measure when using structural MRI in glioma. Uncertainty from imaging causes distress for some patients and their caregivers, while for others it provides an important indicator of disease activity. Any study design that changes imaging regimens should consider the potential for influencing current or planned therapeutic trials, ensure that opportunity costs are measured, and capture indirect benefits and added value. CONCLUSION: Evidence for the value, and therefore utility, of regular interval imaging is currently lacking. Ongoing collaborative efforts will improve trial design and generate the evidence to optimise monitoring imaging biomarkers in standard of care brain tumour management.
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