About this trial
This study is designed to evaluate the role of Oxygen Enhanced (OE) Magnetic resonance imaging (MRI) and Blood Oxygenation Level Dependent (BOLD) MRI in detecting regions of hypoxic tumour and to evaluate their use as imaging methods to selectively deliver targeted radiotherapy to regions of aggressive disease.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Suspected high-grade glioma (HGG) / glioblastoma multiforme (WHO grade IV) at initial radiological examination
Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2
Available for scanning on two separate days
Disqualifiers
Women lactating, pregnant or of childbearing potential who are not willing to avoid pregnancy during the study
Patients with a history of severe renal disease(s) (eGFR <20) that cannot tolerate gadolinium chelate contrast agents.
Geographically remote patients unable to agree to imaging schedule
Patients who have received anti - vascular endothelial growth factor (anti-VEGF) monoclonal antibody therapy the 3 months prior to recruitment
Trial population
Histopathological diagnosis of a high grade glioma / glioblastoma multiforme
Trial design
Case-only
Prospective
Treatments tested in this trial
Not listed
Trial groups
Trial outcomes
Primary outcomes
Determination of spatial correlation of hypoxic tumour volume between Magnetic resonance imaging (MRI) and [18F]-Fluoromisonidazole (18F-FMISO) MRI
Spatial correlation between hypoxic tumour volume determined with MRI and 18F-FMISO will be evaluated via measurements of Dice similarity coefficient. Dice similarity coefficients \> 0.9 will be considered a strong spatial correlation. Quantitative correlation of voxel-wise levels of hypoxia will be evaluated via measurement of the Spearman's/Pearson's correlation coefficient. Correlation coefficients \> 0.7 will be considered a strong correlation.
Secondary outcomes
Repeatability of voxel-wise levels of hypoxia in the tumour
Repeatability of voxel-wise levels of hypoxia in the tumour will be assessed by measurements of intraclass correlation coefficient (ICC).27 ICC values \> 0.9 reflect excellent repeatability, good between 0.75 and 0.9, moderate between 0.5 and 0.75, and poor \< 0.5. Additionally, similarity between the hypoxia tumour volume (HTV) defined with the MRI biomarker at the two timepoints will be assessed via calculation of Dice similarity coefficient. Dice similarity coefficients \> 0.9 will be considered a strong correlation.
The predicted patient outcomes of the biologically-adapted Radiotherapy (RT) plan will be compared with the actual patient outcomes
The predicted patient outcomes of the biologically-adapted RT plan will be compared with the actual patient outcomes following conventional treatment, by using metrics including tumour control probability (TCP) and toxicity measurement to organs at risks and healthy brain (including equivalent uniform dose). Success for this objective will be achieved if the biologically-adapted RT plans result in improved TCP by at least 10% for all patients over conventional treatment, while toxicity metrics remain similar.
Correlation between the percentage of hypoxic tumour volume and clinical outcome
Correlation between the percentage of hypoxic tumour volume and clinical outcome will be evaluated by means of hazard ratio obtained from Cox regression. A hazard ratio \> 1 (p\<0.05) will indicate that the hypoxic tumour volume increase from 13 weeks post chemoradiation therapy (CRT) and recurrence is associated with worst Overall Survival (OS) and Progression Free Survival (PFS).
Correlation between the percentage change of hypoxic tumour volume during treatment and clinical outcome
Correlation between the percentage change of hypoxic tumour volume during treatment and clinical outcome will be evaluated by means of hazard ration obtained from Cox regression. A hazard ratio \> 1 (p\<0.05) will indicate that the increase in hypoxic tumour volume during treatment is associated with worse OS.
Sponsors and contacts
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University of Sydney
Lead sponsor
The Brain Cancer Group
Collaborator