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Title: Evaluation of the Lactate-to-N-Acetyl-aspartate Ratio Defined With Magnetic Resonance Spectroscopic Imaging Before Radiation Therapy as a New Predictive Marker of the Site of Relapse in Patients With Glioblastoma Multiforme

Purpose: Because lactate accumulation is considered a surrogate for hypoxia and tumor radiation resistance, we studied the spatial distribution of the lactate-to-N-acetyl-aspartate ratio (LNR) before radiation therapy (RT) with 3D proton magnetic resonance spectroscopic imaging (3D-{sup 1}H-MRSI) and assessed its impact on local tumor control in glioblastoma (GBM). Methods and Materials: Fourteen patients with newly diagnosed GBM included in a phase 2 chemoradiation therapy trial constituted our database. Magnetic resonance imaging (MRI) and MRSI data before RT were evaluated and correlated to MRI data at relapse. The optimal threshold for tumor-associated LNR was determined with receiver-operating-characteristic (ROC) curve analysis of the pre-RT LNR values and MRI characteristics of the tumor. This threshold was used to segment pre-RT normalized LNR maps. Two spatial analyses were performed: (1) a pre-RT volumetric comparison of abnormal LNR areas with regions of MRI-defined lesions and a choline (Cho)-to- N-acetyl-aspartate (NAA) ratio ≥2 (CNR2); and (2) a voxel-by-voxel spatial analysis of 4,186,185 voxels with the intention of evaluating whether pre-RT abnormal LNR areas were predictive of the site of local recurrence. Results: A LNR of ≥0.4 (LNR-0.4) discriminated between tumor-associated and normal LNR values with 88.8% sensitivity and 97.6% specificity. LNR-0.4 voxels were spatially different frommore » those of MRI-defined lesions, representing 44% of contrast enhancement, 64% of central necrosis, and 26% of fluid-attenuated inversion recovery (FLAIR) abnormality volumes before RT. They extended beyond the overlap with CNR2 for most patients (median: 20 cm{sup 3}; range: 6-49 cm{sup 3}). LNR-0.4 voxels were significantly predictive of local recurrence, regarded as contrast enhancement at relapse: 71% of voxels with a LNR-0.4 before RT were contrast enhanced at relapse versus 10% of voxels with a normal LNR (P<.01). Conclusions: Pre-RT LNR-0.4 in GBM indicates tumor areas that are likely to relapse. Further investigations are needed to confirm lactate imaging as a tool to define additional biological target volumes for dose painting.« less
Authors:
 [1] ;  [2] ;  [3] ;  [1] ;  [2] ;  [4] ; ;  [1] ; ;  [5] ;  [6] ;  [5] ;
  1. Département de Radiothérapie, Institut Claudius Regaud, Toulouse (France)
  2. (Unité Mixte de Recherche) 825, Institut National de la Santé et de la Recherche Médicale, Toulouse (France)
  3. (Institut National Polytechnique), ENVT (Ecole Nationale Vétérinaire de Toulouse), Unité d'Anatomie-Imagerie-Embryologie, Université de Toulouse, Toulouse (France)
  4. Bureau des Etudes Cliniques, Institut Claudius Regaud, Toulouse (France)
  5. UMR (Unité Mixte de Recherche) 825, Institut National de la Santé et de la Recherche Médicale, Toulouse (France)
  6. (Centre Hospitalier Universitaire) de Toulouse, Toulouse (France)
Publication Date:
OSTI Identifier:
22423824
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 90; Journal Issue: 2; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; ANOXIA; BIOMEDICAL RADIOGRAPHY; CHOLINE; COMPARATIVE EVALUATIONS; DIAGNOSIS; GLIOMAS; HYDROGEN 1; LACTATES; MAGNETIC RESONANCE; NECROSIS; NMR IMAGING; PATIENTS; RADIATION DOSES; RADIOTHERAPY; SENSITIVITY; SPATIAL DISTRIBUTION; SPECIFICITY