title: Magnetic resonance spectroscopy as an early indicator of response to anti-angiogenic therapy in patients with recurrent glioblastoma: RTOG 0625/ACRIN 6677.
abstract: BACKGROUND
  The prognosis for patients with recurrent glioblastoma remains poor. The purpose of this study was to assess the potential role of MR spectroscopy as an early indicator of response to anti-angiogenic therapy.
  
  
  METHODS
  Thirteen patients with recurrent glioblastoma were enrolled in RTOG 0625/ACRIN 6677, a prospective multicenter trial in which bevacizumab was used in combination with either temozolomide or irinotecan. Patients were scanned prior to treatment and at specific timepoints during the treatment regimen. Postcontrast T1-weighted MRI was used to assess 6-month progression-free survival. Spectra from the enhancing tumor and peritumoral regions were defined on the postcontrast T1-weighted images. Changes in the concentration ratios of n-acetylaspartate/creatine (NAA/Cr), choline-containing compounds (Cho)/Cr, and NAA/Cho were quantified in comparison with pretreatment values.
  
  
  RESULTS
  NAA/Cho levels increased and Cho/Cr levels decreased within enhancing tumor at 2 weeks relative to pretreatment levels (P = .048 and P = .016, respectively), suggesting a possible antitumor effect of bevacizumab with cytotoxic chemotherapy. Nine of the 13 patients were alive and progression free at 6 months. Analysis of receiver operating characteristic curves for NAA/Cho changes in tumor at 8 weeks revealed higher levels in patients progression free at 6 months (area under the curve = 0.85), suggesting that NAA/Cho is associated with treatment response. Similar results were observed for receiver operating characteristic curve analyses against 1-year survival. In addition, decreased Cho/Cr and increased NAA/Cr and NAA/Cho in tumor periphery at 16 weeks posttreatment were associated with both 6-month progression-free survival and 1-year survival.
  
  
  CONCLUSIONS
  Changes in NAA and Cho by MR spectroscopy may potentially be useful as imaging biomarkers in assessing response to anti-angiogenic treatment.
authors: A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Department of Radiology, Neuroradiology Division, Harvard Medical School, Building 149, 13th Street, Room 2301, Charlestown, MA 02129, USA. ratai@nmr.mgh.harvard.edu
authors: Eva-Maria
authors: EM
authors: Ratai
authors: Zheng
authors: Z
authors: Zhang
authors: Bradley S
authors: BS
authors: Snyder
authors: Jerrold L
authors: JL
authors: Boxerman
authors: Yair
authors: Y
authors: Safriel
authors: Robert C
authors: RC
authors: McKinstry
authors: Felix
authors: F
authors: Bokstein
authors: Mark R
authors: MR
authors: Gilbert
authors: A Gregory
authors: AG
authors: Sorensen
authors: Daniel P
authors: DP
authors: Barboriak
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D000068258:Bevacizumab; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D002794:Choline / Q000378:metabolism; D003401:Creatine / Q000378:metabolism; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005240:Feasibility Studies; D005500:Follow-Up Studies; D005909:Glioblastoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D006801:Humans; D000077146:Irinotecan; D009682:Magnetic Resonance Spectroscopy; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000188:drug therapy / Q000401:mortality; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D011379:Prognosis; D011446:Prospective Studies; D015996:Survival Rate; D000077204:Temozolomide
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D000068258:Bevacizumab; D001224:Aspartic Acid; D000077146:Irinotecan; D003606:Dacarbazine; C000179:N-acetylaspartate; D003401:Creatine; D002794:Choline; D002166:Camptothecin; D000077204:Temozolomide
keywords: Cho; NAA; anti-angiogenic therapy; bevacizumab; glioblastoma; magnetic resonance spectroscopy
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