title: Serial magnetic resonance spectroscopy reveals a direct metabolic effect of cediranib in glioblastoma.
abstract: 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.
authors.affiliation: Massachusetts Institute of Technology, Department of Nuclear Science and Engineering-Health Science and Technology, Cambridge, Massachusetts, USA. heisoog@nmr.mgh.harvard.edu
authors.forename: Heisoog
authors.initials: H
authors.lastname: Kim
authors.forename: Ciprian
authors.initials: C
authors.lastname: Catana
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Ratai
authors.forename: Ovidiu C
authors.initials: OC
authors.lastname: Andronesi
authors.forename: Dominique L
authors.initials: DL
authors.lastname: Jennings
authors.forename: Tracy T
authors.initials: TT
authors.lastname: Batchelor
authors.forename: Rakesh K
authors.initials: RK
authors.lastname: Jain
authors.forename: A Gregory
authors.initials: AG
authors.lastname: Sorensen
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D001932:Brain Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005909:Glioblastoma / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000098:blood supply / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D011799:Quinazolines / Q000008:administration & dosage*; D055815:Young Adult; D007211:Indoles
chemical_list: D020533:Angiogenesis Inhibitors; D011799:Quinazolines; C500926:cediranib; D007211:Indoles