Dataset Information

Integrative Network-based Analysis of Magnetic Resonance Spectroscopy and Genome Wide Expression in Glioblastoma multiforme.

ABSTRACT: The goal of this study was to identify correlations between metabolites from proton MR spectroscopy and genetic pathway activity in glioblastoma multiforme (GBM). Twenty patients with primary GBM were analysed by short echo-time chemical shift imaging and genome-wide expression analyses. Weighed Gene Co-Expression Analysis was used for an integrative analysis of imaging and genetic data. N-acetylaspartate, normalised to the contralateral healthy side (nNAA), was significantly correlated to oligodendrocytic and neural development. For normalised creatine (nCr), a group with low nCr was linked to the mesenchymal subtype, while high nCr could be assigned to the proneural subtype. Moreover, clustering of normalised glutamine and glutamate (nGlx) revealed two groups, one with high nGlx being attributed to the neural subtype, and one with low nGlx associated with the classical subtype. Hence, the metabolites nNAA, nCr, and nGlx correlate with a specific gene expression pattern reflecting the previously described subtypes of GBM. Moreover high nNAA was associated with better clinical prognosis, whereas patients with lower nNAA revealed a shorter progression-free survival (PFS).

SUBMITTER: Heiland DH

PROVIDER: S-EPMC4924099 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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Integrative Network-based Analysis of Magnetic Resonance Spectroscopy and Genome Wide Expression in Glioblastoma multiforme.

Heiland Dieter Henrik DH Mader Irina I Schlosser Pascal P Pfeifer Dietmar D Carro Maria Stella MS Lange Thomas T Schwarzwald Ralf R Vasilikos Ioannis I Urbach Horst H Weyerbrock Astrid A

Scientific reports 20160628

The goal of this study was to identify correlations between metabolites from proton MR spectroscopy and genetic pathway activity in glioblastoma multiforme (GBM). Twenty patients with primary GBM were analysed by short echo-time chemical shift imaging and genome-wide expression analyses. Weighed Gene Co-Expression Analysis was used for an integrative analysis of imaging and genetic data. N-acetylaspartate, normalised to the contralateral healthy side (nNAA), was significantly correlated to oligo ...[more]

PMID: 27350391

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Project description:PurposeTo determine the efficacy of a Gamma Knife stereotactic radiosurgery (SRS) boost to areas of high risk determined by magnetic resonance spectroscopy (MRS) functional imaging in addition to standard radiotherapy for patients with glioblastoma (GBM).Methods and materialsThirty-five patients in this prospective Phase II trial underwent surgical resection or biopsy for a GBM followed by SRS directed toward areas of MRS-determined high biological activity within 2 cm of the postoperative enhancing surgical bed. The MRS regions were determined by identifying those voxels within the postoperative T2 magnetic resonance imaging volume that contained an elevated choline/N-acetylaspartate ratio in excess of 2:1. These voxels were marked, digitally fused with the SRS planning magnetic resonance image, targeted with an 8-mm isocenter per voxel, and treated using Radiation Therapy Oncology Group SRS dose guidelines. All patients then received conformal radiotherapy to a total dose of 60 Gy in 2-Gy daily fractions. The primary endpoint was overall survival.ResultsThe median survival for the entire cohort was 15.8 months. With 75% of recursive partitioning analysis (RPA) Class 3 patients still alive 18 months after treatment, the median survival for RPA Class 3 has not yet been reached. The median survivals for RPA Class 4, 5, and 6 patients were 18.7, 12.5, and 3.9 months, respectively, compared with Radiation Therapy Oncology Group radiotherapy-alone historical control survivals of 11.1, 8.9, and 4.6 months. For the 16 of 35 patients who received concurrent temozolomide in addition to protocol radiotherapeutic treatment, the median survival was 20.8 months, compared with European Organization for Research and Treatment of Cancer historical controls of 14.6 months using radiotherapy and temozolomide. Grade 3/4 toxicities possibly attributable to treatment were 11%.ConclusionsThis represents the first prospective trial using selective MRS-targeted functional SRS combined with radiotherapy for patients with GBM. This treatment is feasible, with acceptable toxicity and patient survivals higher than in historical controls. This study can form the basis for a multicenter, randomized trial.

Dataset Information

Integrative Network-based Analysis of Magnetic Resonance Spectroscopy and Genome Wide Expression in Glioblastoma multiforme.

Publications

Integrative Network-based Analysis of Magnetic Resonance Spectroscopy and Genome Wide Expression in Glioblastoma multiforme.

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