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  • Assessment of Treatment Response in IDH-mutant Gliomas by Quantification of 2-Hydroxyglutarate with in-vivo 3D Magnetic Resonance Spectroscopy

    Final Number:

    Franziska Loebel MD; Daniel P. Cahill MD; Wolfgang Bogner PhD; Malgorzata Marjanska; Elizabeth Gerstner; Tracy Batchelor MD; Bruce R Rosen; Andrew S Chi MD; Ovidiu C Andronesi

    Study Design:
    Laboratory Investigation

    Subject Category:

    Meeting: Congress of Neurological Surgeons 2014 Annual Meeting

    Introduction: Mutations in isocitrate dehydrogenase (IDH) - present in a distinct subset of human gliomas characterized by younger age and improved prognosis- cause a marked elevation of the metabolite 2-hydroxyglutarate (2HG)[1,2]. This excess production of 2HG represents an ideal biomarker for these gliomas and can be measured with in-vivo magnetic resonance spectroscopy [3]. We previously demonstrated that 2HG can be detected reliably in IDH-mutant gliomas with 3D spectral-edited MR spectroscopic imaging (MRSI) [4]. Here, we aimed to show that 3D metabolomic mapping of 2HG can be utilized to evaluate treatment response in IDH-mutant gliomas.

    Methods: 3D metabolomic maps were measured in 18 IDH-mutant glioma patients prior to adjuvant radiation or chemotherapy with a robust and efficient 3D MRSI sequence. All measurements were performed with a whole-body 3T MR scanner (Siemens Tim Trio with VB17 software). Spectra were fitted with LCModel software. All patients with detectable levels of 2HG in the baseline scan were subjected to a post-treatment 3D MRSI to measure changes of 2HG-levels after adjuvant therapy.

    Results: 16 of 18 patients (88.9%) demonstrated detectable levels of 2HG on their baseline scan. Matched pre- and post-treatment 3D metabolomic maps indicated varying response to treatment: 4 patients demonstrated significant reduction of 2HG intensities after radiation therapy (Fig 1), while the remaining patients demonstrated mixed response (partial reduction of 2HG) to adjuvant treatment.

    Conclusions: Assessment of treatment response is feasible with in-vivo 3D MRSI of 2HG in IDH-mutant glioma patients. Significant reduction of 2HG-levels in patients after completion of radiotherapy is suggestive of positive response to treatment. Further validation and longitudinal quantification of 2HG in IDH-mutant gliomas with 3D MRSI is needed to evaluate the ability of the presented approach to reliably determine treatment response. Nevertheless, this non-invasive method yields great potential for clinical applicability and could tremendously improve the management of IDH-mutant glioma patients.

    Patient Care: Longitudinal non-invasive monitoring of 2HG could improve the management of IDH-mutant glioma patients by indicating treatment response and distinguishing treatment effects from progression or tumor recurrence.

    Learning Objectives: By the conclusion of this session, participants should be able to describe different methods for in-vivo spectroscopic assessment of 2HG in IDH-mutant gliomas and evaluate treatment responses in patients using 3D metabolomic maps.

    References: [1] Parsons DW et al. , Science 2008; 321:1807-12., [2] Yan H et al., N Engl J Med 2009; 360(8):765-73., [] [3] Dang L et al., Nature 2009; 462:739-52., [4] Andronesi OC et al., STM 2012; 4:116ra114.,

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