Abstract
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.
Highlights
Glioblastoma (GBM) is the most common and, the most aggressive type of primary malignant brain tumor
The overall survival at 1-year (OS-1) for the 17 evaluable patients was 59% vs. 60% in the larger cohort. These results suggest that the rejection or non-availability of some of the MRSI data has not introduced any significant bias into patient selection that might impact the analysis and results
This study reports the results of the 1H-MRSI data of the American College of Radiology Imaging Network (ACRIN) 6684 multi-center imaging trial to assess tumor hypoxia in GBM using 18F-FMISO PET and MRI
Summary
Glioblastoma (GBM) is the most common and, the most aggressive type of primary malignant brain tumor. Radiation, and chemotherapy, the median overall survival is less than 15 months [1]. Tumor hypoxia limits the efficacy of radiation and chemotherapy and may select for a more aggressive tumor phenotype. It may be a potent stimulator of abnormal angiogenesis [3]. A multi-center imaging trial, “American College of Radiology Imaging Network (ACRIN) 6684: A Multicenter, phase II assessment of tumor hypoxia in Glioblastoma using 18F Fluoromisonidazole (FMISO) with PET and MRI”, was conducted to assess hypoxia in patients with GBM
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