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PLoS One. 2018 Jun 14;13(6):e0198548. doi: 10.1371/journal.pone.0198548. eCollection 2018.

ACRIN 6684: Multicenter, phase II assessment of tumor hypoxia in newly diagnosed glioblastoma using magnetic resonance spectroscopy.

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Department of Radiology, Neuroradiology Division, Massachusetts General Hospital, and Harvard Medical School, Boston, MA, United States.
A. A. Martinos Center for Biomedical Imaging, Charlestown, MA, United States of America.
Center for Statistical Sciences, Brown University, Providence, RI, United States of America.
Department of Radiology, University of Washington, Seattle, WA, United States of America.
Department of Radiology, Wake Forest University, Winston-Salem, NC, United States of America.
Department of Radiology, Mt. Sinai Medical Center, New York, NY, United States of America.
Department of Radiology, Medical College of Wisconsin, Milwaukee, WI, United States of America.
Department of Radiology, UCLA Medical Center, Los Angeles, CA, United States of America.
Department of Radiology, Duke University, Durham, NC, United States of America.
Department of Radiology, University of Pennsylvania, Philadelphia, PA, United States of America.
Massachusetts General Hospital Cancer Center, Boston, and Harvard Medical School, MA, United States of America.


A multi-center imaging trial by the American College of Radiology Imaging Network (ACRIN) "A Multicenter, phase II assessment of tumor hypoxia in glioblastoma using 18F Fluoromisonidazole (FMISO) with PET and MRI (ACRIN 6684)", was conducted to assess hypoxia in patients with glioblastoma (GBM). The aims of this study were to support the role of proton magnetic resonance spectroscopic imaging (1H MRSI) as a prognostic marker for brain tumor patients in multi-center clinical trials. Seventeen participants from four sites had analyzable 3D MRSI datasets acquired on Philips, GE or Siemens scanners at either 1.5T or 3T. MRSI data were analyzed using LCModel to quantify metabolites N-acetylaspartate (NAA), creatine (Cr), choline (Cho), and lactate (Lac). Receiver operating characteristic curves for NAA/Cho, Cho/Cr, lactate/Cr, and lactate/NAA were constructed for overall survival at 1-year (OS-1) and 6-month progression free survival (PFS-6). The OS-1 for the 17 evaluable patients was 59% (10/17). Receiver operating characteristic analyses found the NAA/Cho in tumor (AUC = 0.83, 95% CI: 0.61 to 1.00) and in peritumoral regions (AUC = 0.95, 95% CI 0.85 to 1.00) were predictive for survival at 1 year. PFS-6 was 65% (11/17). Neither NAA/Cho nor Cho/Cr was effective in predicting 6-month progression free survival. Lac/Cr in tumor was a significant negative predictor of PFS-6, indicating that higher lactate/Cr levels are associated with poorer outcome. (AUC = 0.79, 95% CI: 0.54 to 1.00). In conclusion, despite the small sample size in the setting of a multi-center trial comprising different vendors, field strengths, and varying levels of expertise at data acquisition, MRS markers NAA/Cho, Lac/Cr and Lac/NAA predicted overall survival at 1 year and 6-month progression free survival. This study validates that MRSI may be useful in evaluating the prognosis in glioblastoma and should be considered for incorporating into multi-center clinical trials.

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Conflict of interest statement

I have read the journal's policy and the authors of this manuscript have the following competing interests: Dr. Sorensen has been an employee of Siemens Medical Solutions from 2011-2016, and is currently a board member of IMRIS (includes equity stake). He also has two patents assigned to MGH (US patent # 8,698,496 and US patent # 7,512,435). Dr. Andronesi has one patent (US patent #8,698,496). Dr. Schmainda has an ownership interest in Imaging Biometrics LLC. Dr. Barboriak is a member of the GE Medical systems Neuro MRI Advisory Committee. Dr. Mankoff is an advisory for GE Healthcare. Dr. Ratai is a member on the advisory board for BrainSpec, Inc. Erin Greco is currently employed at Novartis Institutes for BioMedical Research, Cambridge, MA, United States. All other authors declare no conflicts of interest. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.

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