The MANGO study: a prospective investigation of oxygen enhanced and blood-oxygen level dependent MRI as imaging biomarkers of hypoxia in glioblastoma

Caterina Brighi; David E J Waddington; Paul J Keall; Jeremy Booth; Kieran O'Brien; Shona Silvester; Jonathon Parkinson; Marco Mueller; Jackie Yim; Dale L Bailey; Michael Back; James Drummond

doi:10.3389/fonc.2023.1306164

The MANGO study: a prospective investigation of oxygen enhanced and blood-oxygen level dependent MRI as imaging biomarkers of hypoxia in glioblastoma

Front Oncol. 2023 Dec 19:13:1306164. doi: 10.3389/fonc.2023.1306164. eCollection 2023.

Authors

Caterina Brighi¹, David E J Waddington¹, Paul J Keall¹, Jeremy Booth^{2

3}, Kieran O'Brien⁴, Shona Silvester¹, Jonathon Parkinson^{5

6}, Marco Mueller⁴, Jackie Yim^{2

6

7}, Dale L Bailey⁸, Michael Back^{2

6}, James Drummond^{2

6

9}

Affiliations

¹ Image X Institute, Sydney School of Health Sciences, The University of Sydney, Sydney, NSW, Australia.
² Department of Radiation Oncology, Northern Sydney Cancer Centre, Royal North Shore Hospital, Sydney, NSW, Australia.
³ Institute of Medical Physics, School of Physics, The University of Sydney, Sydney, NSW, Australia.
⁴ Siemens Healthcare Pty Ltd, Brisbane, QLD, Australia.
⁵ Department of Neurosurgery, Royal North Shore Hospital, Sydney, NSW, Australia.
⁶ The Brain Cancer Group Sydney, St Leonards, NSW, Australia.
⁷ Centre for Health Economics Research and Evaluation, University of Technology Sydney, Sydney, NSW, Australia.
⁸ Department of Nuclear Medicine, Royal North Shore Hospital, Sydney, NSW, Australia.
⁹ Department of Neuroradiology, Royal North Shore Hospital, Sydney, NSW, Australia.

Abstract

Background: Glioblastoma (GBM) is the most aggressive type of brain cancer, with a 5-year survival rate of ~5% and most tumours recurring locally within months of first-line treatment. Hypoxia is associated with worse clinical outcomes in GBM, as it leads to localized resistance to radiotherapy and subsequent tumour recurrence. Current standard of care treatment does not account for tumour hypoxia, due to the challenges of mapping tumour hypoxia in routine clinical practice. In this clinical study, we aim to investigate the role of oxygen enhanced (OE) and blood-oxygen level dependent (BOLD) MRI as non-invasive imaging biomarkers of hypoxia in GBM, and to evaluate their potential role in dose-painting radiotherapy planning and treatment response assessment.

Methods: The primary endpoint is to evaluate the quantitative and spatial correlation between OE and BOLD MRI measurements and [¹⁸F]MISO values of uptake in the tumour. The secondary endpoints are to evaluate the repeatability of MRI biomarkers of hypoxia in a test-retest study, to estimate the potential clinical benefits of using MRI biomarkers of hypoxia to guide dose-painting radiotherapy, and to evaluate the ability of MRI biomarkers of hypoxia to assess treatment response. Twenty newly diagnosed GBM patients will be enrolled in this study. Patients will undergo standard of care treatment while receiving additional OE/BOLD MRI and [¹⁸F]MISO PET scans at several timepoints during treatment. The ability of OE/BOLD MRI to map hypoxic tumour regions will be evaluated by assessing spatial and quantitative correlations with areas of hypoxic tumour identified via [¹⁸F]MISO PET imaging.

Discussion: MANGO (Magnetic resonance imaging of hypoxia for radiation treatment guidance in glioblastoma multiforme) is a diagnostic/prognostic study investigating the role of imaging biomarkers of hypoxia in GBM management. The study will generate a large amount of longitudinal multimodal MRI and PET imaging data that could be used to unveil dynamic changes in tumour physiology that currently limit treatment efficacy, thereby providing a means to develop more effective and personalised treatments.

Keywords: dose painting; glioblastoma; hypoxia imaging; magnetic resonance imaging; radiotherapy; treatment response assessment.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This trial is funded by The Brain Cancer Group, St Leonards, Australia. DW is supported by a Cancer Institute NSW Early Career Fellowship 2019/ECF1015. CB received salary support for this work from the Australian National Health and Medical Research Council Program Grant APP1132471.