A pilot study using dynamic contrast enhanced-MRI as a response biomarker of the radioprotective effect of memantine in patients receiving whole brain radiotherapy
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Philip Wong1, Ilana R. Leppert2, David Roberge1, Karim Boudam1, Paul D. Brown3, Thierry Muanza4, G. Bruce Pike2,5, Jeffrey Chankowsky6 and Catalin Mihalcioiu7
1 Department of Radiation Oncology, Centre Hospitalier de L’Université de Montréal, Montréal, Québec, Canada
2 Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada
3 Department of Radiation Oncology, Division of Radiation Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX, United States of America
4 Department of Oncology, Jewish General Hospital, Montreal, Québec, Canada
5 Departments of Radiology and Clinical Neurosciences, Hotchkiss Brain Institute, University of Calgary, Alberta, Canada
6 Diagnostic Radiology, McGill University Health Center, Montréal, Québec, Canada
7 Department of Oncology, McGill University Health Center, Montreal, Québec, Canada
Philip Wong, email:
Keywords: MRI, biomarker, imaging, radiotherapy, memantine
Received: May 09, 2016 Accepted: May 17, 2016 Published: May 28, 2016
Purpose: This pilot prospective study sought to determine whether dynamic contrast enhanced MRI (DCE-MRI) could be used as a clinical imaging biomarker of tissue toxicity from whole brain radiotherapy (WBRT).
Method: 14 patients who received WBRT were imaged using dynamic contrast enhanced DCE-MRI prior to and at 8-weeks, 16-weeks and 24-weeks after the initiation of WBRT. Twelve of the patients were also enrolled in the RTOG 0614 trial, which randomized patients to the use of placebo or memantine. After the unblinding of the treatments received by RTOG 0614 patients, DCE-MRI measures of tumor tissue and normal appearing white matter (NAWM) vascular permeability (Initial Area Under the Curve (AUC) Blood Adjusted) was analyzed. Cognitive, quality-of-life (QOL) assessment and blood samples were collected according to the patient’s ability to tolerate the exams. Circulating endothelial cells (CEC) were measured using flow cytometry.
Results: Following WBRT, there was an increasing trend in the vascular permeability of tumors (p=0.09) and NAWM (p=0.06) with time. Memantine significantly (p=0.01) reduced NAWM AUC changes following radiotherapy. Patients on memantine retained (COWA p= 0.03) better cognitive functions than those on placebo. No association was observed between the level of CEC and DCE-MRI changes, time from radiotherapy or memantine use.
Conclusions: DCE-MRI can detect vascular damage secondary to WBRT. Our data suggests that memantine reduces WBRT-induced brain vasculature damages.
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