Serial Magnetic Resonance Spectroscopy Reveals a Direct Metabolic Effect of Cediranib in Glioblastoma

• Published in: Cancer research (Chicago, Ill.) Vol. 71; no. 11; pp. 3745 - 3752
• Main Authors: KIM, Heisoog, CATANA, Ciprian, RATAI, Eva-Maria, ANDRONESI, Ovidiu C, JENNINGS, Dominique L, BATCHELOR, Tracy T, JAIN, Rakesh K, SORENSEN, A. Gregory
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01-06-2011
• Subjects: Adult; Aged; Angiogenesis Inhibitors - administration & dosage; Antineoplastic agents; Biological and medical sciences; Brain Neoplasms - blood supply; Brain Neoplasms - drug therapy; Brain Neoplasms - metabolism; Brain Neoplasms - pathology; Female; Glioblastoma - blood supply; Glioblastoma - drug therapy; Glioblastoma - metabolism; Glioblastoma - pathology; Humans; Magnetic Resonance Spectroscopy - methods; Male; Medical sciences; Middle Aged; Neoplasm Recurrence, Local - blood supply; Neoplasm Recurrence, Local - drug therapy; Neoplasm Recurrence, Local - metabolism; Neoplasm Recurrence, Local - pathology; Neurology; Pharmacology. Drug treatments; Quinazolines - administration & dosage; Tumors; Tumors of the nervous system. Phacomatoses; Young Adult; Malignant glioma; Nervous system diseases; Central nervous system disease; Glioblastoma; Metabolic activation; NMR spectrometry; Malignant tumor; Metabolism; Pharmacokinetics; Antiangiogenic agent; Cediranib; Cancer
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.can-10-2991

Proton magnetic resonance spectroscopy is increasingly used in clinical studies of brain tumor to provide information about tissue metabolic profiles. In this study, we evaluated changes in the levels of metabolites predominant in recurrent glioblastoma multiforme (rGBM) to characterize the response of rGBM to antiangiogenic therapy. We examined 31 rGBM patients treated with daily doses of cediranib, acquiring serial chemical shift imaging data at specific time points during the treatment regimen. We defined spectra from three regions of interest (ROI)--enhancing tumor (ET), peritumoral tissue, and normal tissue on the contralateral side (cNT)--in post-contrast T1-weighted images, and normalized the concentrations of N-acetylaspartate (NAA) and choline (Cho) in each ROI to the concentration of creatine in cNT (norCre). We analyzed the ratios of these normalized metabolites (i.e., NAA/Cho, NAA/norCre, and Cho/norCre) by averaging all patients and categorizing two different survival groups. Relative to pretreatment values, NAA/Cho in ET was unchanged through day 28. However, after day 28, NAA/Cho significantly increased in relation to a significant increase in NAA/norCre and a decrease in Cho/norCre; interestingly, the observed trend was reversed after day 56, consistent with the clinical course of GBM recurrence. Notably, receiver operating characteristic analysis indicated that NAA/Cho in tumor shows a high prediction to 6-month overall survival. These metabolic changes in these rGBM patients strongly suggest a direct metabolic effect of cediranib and might also reflect an antitumor response to antiangiogenic treatment during the first 2 months of treatment. Further study is needed to confirm these findings.