MRS of Glioma Genomics

Official title

Magnetic Resonance Spectroscopy Markers of Glioma Genomics

Overview

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.

Interventions

• Diagnostic test MRI
  MRI without contrast agent

Primary outcome measures

• Metabolite concentrations by MRS [Time frame: 1.5 hour]

Secondary outcome measures (3)

• Diffusion MRI metrics [Time frame: 1,5 hours]
• Metabolic changes during an anti-tumor treatment [Time frame: 1 year]
• Diffusion MRI and amide proton transfer signal changes during an anti-tumor treatment. [Time frame: 1 year]

Eligibility criteria

Inclusion criteria

• Affiliations to a social security scheme (as a beneficiary or a person entitled to benefits)
• Obtainig written, informed consent
• One of the following two situations

• Group 1 : Probable grade II/III/IV glioma, for which excision is scheduled.
• Group 2 : Histologically confirmed grade II or III glioma with known IDH1/IDH2 status, which has received no treatment other than surgery and is due to undergo therapy other than surgery.
• Presence of measurable tumor residue (>2 cm in diameter on FLAIR imaging)
• Karnofsky Index > 60
• Effective contraception throughout the study, supplemented by a negative pregnancy test for women of childbearing age.

Exclusion criteria

• Containdications to MRI : Pacemaker or neural stimulators, intraocular or intracerebral metallic foreign bodies, cochlear implant, heart valve or metallic surgical arterial devices that are not MRI ompatible, metallic devices susceptible to concentrating radio-frequency pulses, claustrophobia

• Pregnant or breastfeeding women
• Regulatory criteria :

Pregnant women, women in labor, breastfeeding women ; Failure to sign the consent form or paticipant refusal ; Legal protection measures (guardianship, curatorship, judicial protection) ; Participation in another research study that does not allow for compliance with the exclusion period between the two studies ; Individuals not covered by a health insurance scheme.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Basic science

Study locations

France · 2 centers

• Pitié-Salpetrière Hospital — Paris
• Hôpital Pitié Salpêtrière, 47 Boulevard de l'Hôpital, 75013 Paris — Paris

Identifiers

NCT: NCT05700071 · C21-27 · 2021-A03015-36

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗