MRS of Glioma Genomics

Study Overview
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Brief Summary
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In France, about 5000 new people with a primary malignant brain tumor are diagnosed each year. The most common primary tumors are gliomas, originating from glial cells (astrocytomas and oligodendrogliomas). Low-grade gliomas are mildly aggressive, but they often evolve into a more malignant form. Mutations in the genes encoding isocitrate dehydrogenase (IDH) are found in about 80% of low-grade gliomas and are associated with a favorable prognosis. Remarkably, IDH-mutated gliomas are characterized by a specific cellular metabolism causing the accumulation of D-2-hydroxyglutarate (2HG) in tumor cells. 2HG can be detected in vivo using 1H magnetic resonance spectroscopy (MRS) and is recognized as a unique, noninvasive biomarker of IDH-mutated gliomas. Noninvasive detection of IDH mutations via 2HG MRS represents a crucial step for decision-making and patient care. A subset of IDH-mutated tumors also presents a complete deletion of 1p and 19q chromosome arms (1p/19q codeletion). The 1p/19q codeletion is specifically linked to the oligodendroglial histologic subtype and it has been associated with a better patient outcome. However, the biological effects of this genetic alteration are still unclear and in vivo markers are lacking. Recently, we reported the first in vivo detection of the cystathionine molecule in human brain gliomas using MRS and explored the association between cystathionine accumulation and 1p/19q codeletion in gliomas. In this project, the investigation team will combine cutting edge MRI and MRS techniques for metabolic and microstructural characterization of brain tumors with the aim of providing novel reliable noninvasive biomarkers of tumor genetic subtypes. These methods will enable noninvasive identification of IDH-mutated gliomas and, potentially, 1p/19q codeleted gliomas. In addition, the researchers will investigate the utility of 2HG, cystathionine and MRI microstructural markers to monitor tumor response to anti-cancer treatments and tumor progression. The outputs of this project, altogether, may open new avenues to a better understanding of the pathophysiological mechanisms of oncogenesis and the design of new treatments for gliomas.

Official Title
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Magnetic Resonance Spectroscopy Markers of Glioma Genomics

Conditions
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Glioma

Intervention / Treatment
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* Diagnostic Test: MRI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Affiliation à un régime de sécurité sociale (bénéficiaire ou ayant droit) Recueil du consentement écrit et éclairé Une des deux situations suivantes : Groupe 1 : Probable gliome de grade II/III, dont l'exérèse est programmée Groupe 2 : gliome de grade II ou III prouvé histologiquement avec statut IDH1/IDH2 connu, n'ayant reçu aucun autre traitement que la chirurgie, et devant débuter un traitement autre que la chirurgie. Présence d'un résidu tumoral évaluable (>2 cm de diamètre en FLAIR) Index de Karnofsky > 60 Contraception efficace pendant la durée de la recherche, complété par un test de grossesse négatif pour les femmes en âge de procréer. Exclusion Criteria: Contrindications à l'IRM: pace maker ou stimulateur neuronal, corps étranger métallique intraoculaire ou intracérébral, implant cochléaire, valve cardiaque ou matériel artériel chirurgical métallique non compatible IRM, matériel métallique susceptible de concentrer les impulsions de radio fréquence, claustrophobie femmes enceintes ou allaitantes Critères réglementaires : Femme enceinte, parturiente, allaitante; Absence de signature du consentement ou refus du participant; Mesure de protection juridique (tutelle, curatelle, sauvegarde de justice); Participation à une autre recherche ne permettant pas de respecter la période; d'exclusion entre les 2 recherches; Personne ne bénéficiant pas d'un régime d'assurance maladie

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MRI examination<br> | Diagnostic Test: MRI<br>* MRI without contrast agent<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Metabolite concentrations by MRS | Concentrations of 2-hydroxyglutarate and cystahionine measured by MRS will be correlated with IDH mutational status and 1p19q codeletion derived from ex vivo analyses in tumor tissue samples | 1.5 hour | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diffusion MRI metrics | Diffusion MRI metrics will be correlated with the 1p19q codeletion status derived from ex vivo analyses in tumor tissue samples | 1,5 hours | 
| Metabolic changes during an anti-tumor treatment | The changes in concentration of 2-hydroxyglutarate, cystathionine and choline will be compared to the changes in tumor volumes and to the clinical response | 1 year | 
| Diffusion MRI and amide proton transfer signal changes during an anti-tumor treatment. | Diffusion MRI and amide proton transfer signal changes will be compared to the changes in metabolism, tumor volumes and to the clinical response | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gliomas, Isocitrate dehydrogenase, 1p19q codeletion, MR Spectroscopy, MRI, Diagnosis, Treatment monitoring