Using the Chemical Modifications Present on RNA Molecules to Diagnose and Treat Brain Cancer
NCT Number: NCT06575452
Acronym: EPIGLIO
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: NA
Conditions: Glioma
Interventions: DIAGNOSTIC_TEST: Blood, urine and tumoral tissue samples|DIAGNOSTIC_TEST: Tumoral tissue samples
Sponsor: Institut du Cancer de Montpellier - Val d'Aurelle
Collaborators: National Cancer Institute, France
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 228
Study Design: Allocation: NON_RANDOMIZED|Intervention Model: PARALLEL|Masking: NONE|Primary Purpose: DIAGNOSTIC
Start Date: 2024-11
Completion Date: 2028-04
Locations: Insitut Régional du Cancer de Montpellier, Montpellier, Hérault, 34298, France|CHU Montpellier - Hôpital St Eloi, Montpellier, 34090, France

Summary:
Diffuse gliomas are among the most common tumors of the central nervous system, with high morbidity and mortality and very limited therapeutic possibilities. The diffuse glioma are characterized by significant variability in terms of age at diagnosis, histological and molecular features, classification, ability to transform to a higher grade and/or to disseminate in the brain, response to treatment and patient outcome.

One of the main challenges in the management of diffuse gliomas is related to tumor heterogeneity within the same subgroup. Establishing an accurate tumor classification is of paramount importance for selecting personalized therapy or avoiding unnecessary treatment.

At present, the main diagnostic methods for detecting gliomas are based on histopathological features and mutation detection. Yet difficulties remain, due to tumor heterogeneity and sampling bias for tumors obtained from small biopsies. In particular, grade 2 (low-grade) and grade 3 (high-grade) gliomas cannot be easily distinguished, as intra-tumoral tumor grade heterogeneity is not uncommon in patients treated with extensive surgical resection. Another challenge in the field of gliomas is longitudinal monitoring of disease progression, which is currently mainly based on repeated brain Magnetic Resonance Imaging (MRI). New tools to detect tumor changes before the onset of imaging changes would be useful.

Several genetic, epigenetic, metabolic and immunological profiles have been established for gliomas. Recently, the world of RiboNucleic Acid (RNA) has emerged as a promising area to explore for cancer therapy, especially since the (re)discovery of RNA chemical modifications. To date, more than 150 types of post-transcriptional modifications have been reported on various RNA molecules. This complex landscape of chemical marks embodies a new, invisible code that governs the post-transcriptional fate of RNA: stability, splicing, storage, translation.

Primary Outcome Measures: Sensitivity of RNA-modified nucleoside expression marks for glioma diagnosis vs controls in blood for patients in cohort 1., Sensitivity of a test corresponds to its ability to give a positive result when the hypothesis is verified., At baseline, 3 months, 9 months and 18 months|Specificity of RNA-modified nucleoside expression marks for glioma diagnosis vs controls in blood for patients in cohort 1., Specificity measures the ability of a test to give a negative result when the hypothesis is not verified., At baseline, 3 months, 9 months and 18 months|Positive Predictive Value (PPV) of modified nucleoside expression marks for the diagnosis of glioma vs. controls in blood for patients in cohort 1., Predictive value of a test is the probability of a condition being present as a function of the test result., At baseline, 3 months, 9 months and 18 months|Negative Predictive Value (NPV) of modified nucleoside expression marks for the diagnosis of glioma vs. controls in blood for patients in cohort 1., Negative predictive value is the probability that the condition is not present when the test is negative., At baseline, 3 months, 9 months and 18 months
Secondary Outcome Measures: Sensitivity of RNA-modified nucleoside expression marks for glioma diagnosis vs controls in urine for patients in cohort 1., The sensitivity of a test corresponds to its ability to give a positive result when the hypothesis is verified., At baseline, 3 months, 9 months and 18 months|Specificity of RNA-modified nucleoside expression marks for glioma diagnosis vs controls in urine for patients in cohort 1., Specificity measures the ability of a test to give a negative result when the hypothesis is not verified., At baseline, 3 months, 9 months and 18 months|Positive Predictive Value (PPV) of modified nucleoside expression marks for the diagnosis of glioma vs. controls in urine for patients in cohort 1., Predictive value of a test is the probability of a condition being present as a function of the test result., At baseline, 3 months, 9 months and 18 months|Negative Predictive Value (NPV) of modified nucleoside expression marks for the diagnosis of glioma vs. controls in urine for patients in cohort 1., Negative predictive value is the probability that the condition is not present when the test is negative., At baseline, 3 months, 9 months and 18 months|Negative Predictive Value (NPV) of modified nucleoside expression marks for the diagnosis of glioma vs. controls in tumoral tissue for patients in cohort 1 and 2., Negative predictive value is the probability that the condition is not present when the test is negative., At surgery, day 0|Progression-free survival, The progression is determined by RANO criteria. The RANO criteria divide radiological response into four types, based on imaging (MRI) and clinical features 1,2 :

* complete response,
* partial response,
* stable disease,
* Progression., Time from histological diagnosis to date of progression according to the Response Assessment in Neuro-Oncology Criteria (RANO 2.0) or death from any cause, assessed up to 18 months.|Global survival, Time from histological diagnosis to the date of death, whatever the cause, assessed up to 18 months.|The best response according to RANO 2.0, The RANO criteria divide radiological response into four types, based on imaging (MRI) and clinical features 1,2 :

* complete response,
* partial response,
* stable disease,
* Progression., Time from surgery to magnetic response imagery (MRI) showing best response, assessed up to 18 months.|Quantitative value obtained by Liquid Chromatography-Mass Spectrometry (LC-MS) for each post-transcriptional modification (mark) of RiboNucleic Acid (RNA) in cohort 3, Modified nucleoside expression marks in grade 2 tissue versus grade 3 or 4 focus. Nucleoside is a constituent element of nucleic acids, made up of a nitrogenous base associated with a sugar (ribose for RNA and deoxyribose for DNA).

Liquid chromatography-mass spectrometry (LC-MS) is an analytical method that combines the performance of liquid chromatography and mass spectrometry to precisely identify and/or quantify a wide range of substances.

An LC-MS unit comprises two main components: a liquid chromatograph and a mass spectrometer., At baseline, 3 months, 9 months and 18 months|Immunohistochemical detection of the Alpha-thalassemia-X-linked intellectual disability (ATRX) protein, Anti-ATRX immunostaining was classified into four semi-quantitative categories:

* Conserved expression (nuclear labeling of more than 90% of tumor cells),
* Total loss of expression (loss of expression by more than 90% of tumor cells),
* Partial loss of expression (labeling of 10-90% of tumor cells),
* Uninterpretable immunostaining (due to small or unrepresentative material)., At surgery, Day 0|Tumor grading and classification, Grade 2 : low-grade tumor Grade 2 : low-grade tumor Grade 4 : high-grade tumor, the most agressive Grade 3 : high-grade tumor, At surgery, Day 0|Immunohistochemical detection of kiel 67 (KI67) protein, Ki-67 is routinely detected on paraffin-embedded sections with an antibody, and its level calculated by evaluating the nuclear labeling of 1000 tumor cells, i.e. 100 cells/10 large fields (GC), with a positivity threshold above 5%., At surgery, Day 0 of our timeline|Sensitivity of RNA-modified nucleoside expression marks for glioma diagnosis vs controls in tumoral tissue for patients in cohort 1 and 2., The sensitivity of a test corresponds to its ability to give a positive result when the hypothesis is verified., At Surgery, day 0 of our timeline|Specificity of RNA-modified nucleoside expression marks for glioma diagnosis vs controls in tumoral tissue for patients in cohort 1 and 2., Negative predictive value is the probability that the condition is not present when the test is negative., At Surgery, day 0 of our timeline|Positive Predictive Value (PPV) of modified nucleoside expression marks for the diagnosis of glioma vs. controls in tumoral tissue for patients in cohort 1 and 2., Predictive value of a test is the probability of a condition being present as a function of the test result., At surgery, day 0 of our timeline|Immunohistochemical detection of the isocitrate DeHydorgenase (IDH) mutated protein, Anti-IDH immunostaining was classified into two qualitative categories: positive or negative. When the mutation is present, all tumor cells express the mutated protein. Cytoplasmic immunopositivity predicts the presence of the mutation at position R132 of isocitrate dehydrogenase 1 (IDH1)., At surgery, Day 0 of our timeline|Measurement of mean tumor diameter (MTD) spontaneous growth rate by magnetic resoance imaging (MRI), Calculated in mm/year, Assessed during follow-up, up to 18 months|Determination of the quality of surgical resection by magnetic resonance imaging (MRI), The radiologist will assess whether the tumour resection margins are healthy or invaded by tumour foci, After surgery, approximately 30 days|Determination of tumor volume in cm3 by magnetic resonance imaging, Tumor volume (cm3) determined by manual segmentation of tumor contours and mean tumor diameter MTD (calculated according to the formula MTD = (2x volume)1/3) at baseline and during follow-up for the prospective cohort., At baseline and during follow-up, assessed up to 18 months|Magnetic resonance imaging (MRI) evaluation of tumor invasion of soft meninges (leptomeningeal), On MRI, the radiologist will assess whether the soft meninges have been invaded by the tumour, At baseline|Magnetic resonance imaging (MRI) determination of the number of tumor foci in the brain, The radiologist will assess the number of tumor foci per patient. Two groups will be created: unifocal (1 single tumor site) versus plurifocal (several tumor sites)., At baseline|Existence of contrast (gadolinium) zone determined on magnetic resonance imaging (MRI), Tumor zone appearing dark on imaging versus lighter healthy zone, At baseline