Alexandra Deviers1, Soléakhéna Ken2, Thomas Filleron3, Benjamin Rowland4, Andrea Laruelo4, Isabelle Catalaa5, Vincent Lubrano5, Pierre Celsis6, Isabelle Berry7, Giovanni Mogicato8, Elizabeth Cohen-Jonathan Moyal9, Anne Laprie10. 1. Département de Radiothérapie, Institut Claudius Regaud, Toulouse, France; UMR (Unité Mixte de Recherche) 825, Institut National de la Santé et de la Recherche Médicale, Toulouse, France; INP (Institut National Polytechnique), ENVT (Ecole Nationale Vétérinaire de Toulouse), Unité d'Anatomie-Imagerie-Embryologie, Université de Toulouse, Toulouse, France. 2. Département de Radiothérapie, Institut Claudius Regaud, Toulouse, France; UMR (Unité Mixte de Recherche) 825, Institut National de la Santé et de la Recherche Médicale, Toulouse, France. 3. Bureau des Etudes Cliniques, Institut Claudius Regaud, Toulouse, France. 4. Département de Radiothérapie, Institut Claudius Regaud, Toulouse, France. 5. UMR (Unité Mixte de Recherche) 825, Institut National de la Santé et de la Recherche Médicale, Toulouse, France; Hôpital de Rangueil, CHU (Centre Hospitalier Universitaire) de Toulouse, Toulouse, France. 6. UMR (Unité Mixte de Recherche) 825, Institut National de la Santé et de la Recherche Médicale, Toulouse, France. 7. UMR (Unité Mixte de Recherche) 825, Institut National de la Santé et de la Recherche Médicale, Toulouse, France; Hôpital de Rangueil, CHU (Centre Hospitalier Universitaire) de Toulouse, Toulouse, France; Université Toulouse III Paul Sabatier, Toulouse, France. 8. UMR (Unité Mixte de Recherche) 825, Institut National de la Santé et de la Recherche Médicale, Toulouse, France; INP (Institut National Polytechnique), ENVT (Ecole Nationale Vétérinaire de Toulouse), Unité d'Anatomie-Imagerie-Embryologie, Université de Toulouse, Toulouse, France. 9. Département de Radiothérapie, Institut Claudius Regaud, Toulouse, France; UMR1037, CRCT, Institut National de la Santé et de la Recherche Médicale, Toulouse, France; Université Toulouse III Paul Sabatier, Toulouse, France. 10. Département de Radiothérapie, Institut Claudius Regaud, Toulouse, France; UMR (Unité Mixte de Recherche) 825, Institut National de la Santé et de la Recherche Médicale, Toulouse, France. Electronic address: laprie.anne@iuct-oncopole.fr.
Abstract
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-(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 from 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(3); range: 6-49 cm(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.
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-(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 from 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(3); range: 6-49 cm(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.
Authors: Soléakhéna Ken; Alexandra Deviers; Thomas Filleron; Isabelle Catalaa; Jean-Albert Lotterie; Jonathan Khalifa; Vincent Lubrano; Isabelle Berry; Patrice Péran; Pierre Celsis; Elizabeth Cohen-Jonathan Moyal; Anne Laprie Journal: J Neurooncol Date: 2015-07-19 Impact factor: 4.130
Authors: Jeffrey D Rudie; Andreas M Rauschecker; R Nick Bryan; Christos Davatzikos; Suyash Mohan Journal: Radiology Date: 2019-01-22 Impact factor: 11.105