Neoplasms

All Conditions

Nervous System Diseases

Rare Diseases

Glioma

Brain Neoplasms

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Neuroepithelioma

Patients who have suspected or confirmed gliomas and are scheduled to undergo biopsy or resection of their brain tumors will receive a 3 Tesla (3T) Magnetic Resonance Imaging (MRI) scan of their brain.

3T MRI Scanner providing Mega-laser sequence for single-voxel Magnetic Resonance Spectroscopy (MRS) data for 2 hydroxyglutarate (2HG) quantitation.

3T MRI Scanner

Nathalie Padron

Macarena De La Fuente, MD

MRI-based sequences can provide non-invasive quantification of intratumoral 2-hydroxyglutarate (2HG) distribution and tumor cellularity in human gliomas and help guide the development of novel glioma therapies.

This is a pilot study aiming at developing and optimizing MRI-based sequences to provide non-invasive quantification of intratumoral 2-hydroxyglutarate (2HG) distribution and tumor cellularity in human gliomas and help guide the development of novel glioma therapies.

Non-invasive Glioma Characterization Through Molecular Imaging

Pilot Study for Non-invasive Glioma Characterization Through Molecular Imaging

2HG concentrations as measured via 3T MRI Scanner.

2HG concentrations as measured via patient's surgically excised tissue sample ex vivo by tissue based liquid chromatography-mass spectrometry (LC-MS)

University of Miami

Assistance Professor

Monitoring of quantitative levels of 2-hydroxyglutarate (2-HG) via proton magnetic resonance spectroscopy (1H-MRS)

Research proton MRS (1H-MRS)followed by DW-MRI

3T MRI scanner

NCI NOB Referral Group

Jing Wu, M.D.

For more information at the NIH Clinical Center contact National Cancer Institute Referral Office

Background:

Glioma is a type of brain cancer. Some of these tumors have gene mutations. These mutations can cause a substance called 2-HG to build up in the brain. This makes the tumors more aggressive. Researchers want to better understand 2-HG buildup in the brain. They hope this can help them design better ways to test for gliomas.

Objective:

To monitor the level of 2-HG in the brains of people with gliomas that have mutations in the IDH1 or IDH2 genes.

Eligibility:

People ages 18 and older with gliomas with mutations in the IDH1 or IDH2 genes

Design:

Participants will be screened with:

Medical and cancer history

Physical exam

Reviews of their symptoms and ability to perform normal activities

Blood and urine tests

MRI scan

Samples of their tumor from a past surgery

Documentation of their diagnosis and mutation status

Participants will have an initial evaluation. This will include repeats of screening tests. It will also include:

Neurological exam

MRS and MRI scans of the brain: Participants will lie on a table that slides into a metal cylinder. A coil or soft padding will be placed around their head. They will have a contrast agent injected into a vein. Pictures will be taken of the brain.

Participants will have follow-up visits every 2-6 month for the rest of their life. Visits will include scans.

Background:

* Glioma is the most common malignant brain tumor. Genes coding for isocitrate dehydrogenase (IDH), a metabolic enzyme, are frequently mutated in gliomas, particularly lower-grade gliomas (LGGs). IDH mutation causes a unique tumor biology, including the accumulation of 2-hydroxyglutarate (2-HG), an oncometabolite, which in turn causes genomic hypermethylation and tumorigenesis.
* Despite having a better prognosis compared to their IDH WT counterparts, IDH-mutant LGGs undergo a slow but unremitting higher-grade transformation (HT) and eventually become high grade gliomas (HGGs). A subset of patients with transformed HGGs develop a hypermutator phenotype (HMP), possibly related to previous treatment with alkylating agents and radiotherapy. The timeline for the development of HT and HMP is unpredictable and there is no known way to prevent them from happening, largely due to a lack of understanding their biological mechanisms and lack of a non-invasive approach for potential early detection.
* Proton magnetic resonance spectroscopy (MRS) of the brain can detect 2-HG in a tumor harboring IDH mutation. There has been an increased interest in using quantitative 2-HG by MRS as a biomarker for IDH-mutant gliomas. This clinical study will allow a longitudinal monitoring of quantitative 2-HG by MRS in patients with IDH-mutant gliomas. We hypothesize that a significant increase in 2HG level is correlated with HT and/or HMP. The change in 2-HG level in conjunction with evaluation of tumor cellularity and other metabolite markers such as choline, creatinine and N-acetyl aspartate (NAA) will likely to provide insights into metabolic alterations that may correlate with HT/HMP and potentially provide the predictive biomarker for early detection of HT.

Objective:

-To monitor the quantitative levels of 2-hydroxyglutarate (2-HG) longitudinally in patients with IDH-mutant gliomas via proton magnetic resonance spectroscopy (1H-MRS).

Eligibility:

* IDH 1 or 2 mutation confirmed by DNA sequencing.
* Age greater than or equal to18 years, KPS greater than or equal to 60%

Design:

* This is prospective observational study. We will recruit at least 250 eligible patients in the next 5 years.
* The relationship between the occurrence of HT and the changes in 2-HG level using the proportional hazard model.

Studying the Biology of IDH-mutant Gliomas Via Longitudinal Observation of 2-hydroxyglutarate (2-HG) Using MR Spectroscopy

Studying the Biology of IDH-mutant Gliomas Via Longitudinal Observation of 2-Hydroxyglutarate (2-HG) Using MR Spectroscopy

.BTRIS: All IPD recorded in the medical record will be shared with intramural investigators upon@@@@@@request.@@@@@@dbGaP: All large scale genomic sequencing data will be shared with subscribers to dbGaP.

Changes in the level of 2-HG correlate with the occurrence of higher-grade transformation (HT) and/or development of hypermutator phenotype (HMP) in patients with IDH-mutant gliomas

Usefulness of 2-HG detection and its correlation with high grade transformation and HMP

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Non-invasive Glioma Characterization Through Molecular Imaging	NCT03684109	Glioma Brain Tumor Primary Brain T... Malignant Gliom... Malignant Prima...	3T MRI Scanner	18 Years -	University of Miami
Studying the Biology of IDH-mutant Gliomas Via Longitudinal Observation of 2-hydroxyglutarate (2-HG) Using MR Spectroscopy	NCT03952598	Glioma Gliomas High Grade Glio... Malignant Gliom... Low Grade Gliom...	3T MRI scanner	18 Years -	National Institutes of Health Clinical Center (CC)

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