Study of the Capacity of the MRI Spectroscopy to Define the Tumor Area Enriched in Glioblastoma Stem Cells. Proof of Concept Study

This is a prospective biomedical study of interventional type which includes 16 patients on 52 months (24 months of inclusion and 28 months of follow up). This pilot study, combining a metabolic imaging approach (Proton Magnetic Resonance Spectroscopy = 1HMRSI) and a biological one, will be performed in patients harbouring a Glioblastoma (GBM)to determine whether MRI markers of aggressiveness (CNI2) are associated with specific biological patterns as regards to GBMSC (GBM contains tumor stem cell). In the first part of the study, patients with radiological criteria of GBM amenable to surgical resection will be included ; pre-operative multimodal MRI scans will be done and all data acquired (including H1MRS and DTI data) will be integrated in the image-guided surgical device (ie neuronavigation system) to be used intraoperatively. During tumor resection, tissue samples will be individualized, based on their multimodal imaging characteristics and sent to the radiobiology laboratory INSERM for biological analysis. After surgery, patient will be treated by the standard radio-chemotherapy stupp protocol and will be followed according to standard practices; multimodal MRI will be performed every 2 months during the first year and then every 3 months until progression.

Sex

All

Minimum age

18 Years

Inclusion Criteria:

First part of the study (Surgery and Imagery):

1. Surgical indication for patients who present radiological criteria of glioblastoma.
2. Patient who are ≥18 years old
3. Patient must have performance status between 0 and 2 on the ECOG Performance Scale
4. Life expectancy ≥ 3 months
5. Patient affiliated to social security regimen
6. Patient has voluntarily agreed to participate by giving written informed consent for the first part of the study.

Second part of the study (Treatment and Biology):

1. Histologically confirmed glioblastoma
2. Patient must have performance status between 0 and 2 on the ECOG Performance Scale or 3 only is due to motor deficit.
3. Life expectancy ≥ 3 months
4. Patient affiliated to social security regimen
5. Patient has voluntarily agreed to participate by giving written informed consent for the second part of the study.

Exclusion Criteria:

First part of the study (Surgery and Imagery):

1. Patients who are not allowed to perform an MRI
2. Spectroscopic exam whose results are not contributive
3. Pregnant or nursing patient,
4. Patients under law protection
5. Patient who presents conditions that would interfere with cooperation with the requirements of the trial.
6. Patient who presents medical, severe or chronic biological or psychiatric conditions not allowing his enrolment in the study, according to the investigator's opinion

Second part of the study (Treatment and Biology):

1.Biological material received in the lab more than 48 hours after surgery.

• RESULTLemarie A, Lubrano V, Delmas C, Lusque A, Cerapio JP, Perrier M, Siegfried A, Arnauduc F, Nicaise Y, Dahan P, Filleron T, Mounier M, Toulas C, Cohen-Jonathan Moyal E. The STEMRI trial: Magnetic resonance spectroscopy imaging can define tumor areas enriched in glioblastoma stem-like cells. Sci Adv. 2023 Nov 3;9(44):eadi0114. doi: 10.1126/sciadv.adi0114. Epub 2023 Nov 3. PMID 37922359
• DERIVEDPinto G, Saenz-de-Santa-Maria I, Chastagner P, Perthame E, Delmas C, Toulas C, Moyal-Jonathan-Cohen E, Brou C, Zurzolo C. Patient-derived glioblastoma stem cells transfer mitochondria through tunneling nanotubes in tumor organoids. Biochem J. 2021 Jan 15;478(1):21-39. doi: 10.1042/BCJ20200710. PMID 33245115