IDH glioma refers to a subtype of glioma characterized by mutations in the isocitrate dehydrogenase (IDH) genes, specifically IDH1 and IDH2.
These mutations are a key diagnostic and prognostic marker in gliomas.
Adult low-grade gliomas diffusely infiltrate the brain and are defined by the presence of somatic variants in the genes encoding isocitrate dehydrogenase: IDH1 located on chromosome two and IDH2 is located on chromosome 15.
Mutations in IDH disrupt cellular metabolism, induce, DNA methylation, and change chromatin structure.
IDH mutations are most commonly found in lower-grade gliomas (WHO grades II and III) and secondary glioblastomas, which evolve from these lower-grade tumors.
IDH mutant gliomas include astrocytoma grades 2 to 4 and oligodendroglioma grade two and three, the latter is defined by additional chromosome 1p, and 19 codeletion.
The most frequent mutation in IDH1 is at codon R132, particularly the R132H variant, while IDH2 mutations typically occur at codon R172.
These mutations lead to the production of the oncometabolite 2-hydroxyglutarate, which contributes to tumorigenesis through epigenetic dysregulation and altered cellular metabolism.
Clinically, IDH-mutant gliomas are associated with a better prognosis compared to their IDH wild-type counterparts.
Patients with IDH-mutant gliomas generally have longer overall survival and better responses to therapy, including combined radiotherapy and chemotherapy.
The presence of IDH mutations also influences the tumor’s immune microenvironment, which may affect treatment responses.
IDH mutant glioma refers to a type of brain tumor called a glioma that carries a mutation in the isocitrate dehydrogenase (IDH) gene.
This mutation is found in a subset of gliomas and is associated with specific characteristics and prognosis.
Gliomas are tumors that arise from the glial cells in the brain and can be classified based on genetic mutations, including the IDH mutation.
IDH mutant gliomas tend to have a better prognosis compared to gliomas without this mutation.
Patients with IDH mutant gliomas may respond differently to certain treatments and may have different overall outcomes.
Treatment for IDH mutant gliomas typically involves a combination of surgery, radiation therapy, and chemotherapy.
Isocitrate dehydrogenase (IDH) mutations are disease-defining mutations in IDH-mutant astrocytomas and Oligodendroglioma IDH-mutant.
In more than 80% of these tumors, point mutations in IDH type 1 (IDH1) lead to the expression of the tumor-specific protein IDH1R132H.
Approximately 2500 persons in the US have a diagnosis of IDH – mutated grade 2 glioma each year.
These grade 2 gliomas become refractory treatment, and are eventually fatal.
IDH1R132H harbors a major histocompatibility complex class II (MHCII)-restricted neoantigen.
High-grade gliomas with mutations in the isocitrate dehydrogenase (IDH) gene family confer longer overall survival relative to their IDH wild type counterparts.
Accurate determination of the IDH genotype preoperatively may have both prognostic and diagnostic values.
Isocitrate dehydrogenase (IDH) is a key factor in metabolism and catalyzes the oxidative decarboxylation of isocitrate.
Mutations in IDH genes are observed in over 70% of low-grade gliomas and some cases of glioblastoma.
Tumor histology, size and IDH-mutation status are important predictors for prolonged overall survival in patients with low-grade glioma and may provide a reliable tool for treatment strategies.
Prognosis of Grade II and III glioma is better in patients with an IDH mutation than in those without mutation.
Gliomas, the most common primary brain tumors, are characterized by isocitrate dehydrogenase 1 mutation (IDH1-M).
High mutation frequency of IDH1 indicates its promoting role in tumorgenesis.
Patients with IDH1-M have better survival comparing with patients with IDH1 wild-type (IDH1-W).
IDH-mutant gliomas may appear as a well-defined, low-grade mass with irregular borders and a heterogeneous appearance, may show a swiss cheese appearance on imaging, with small cystic areas within the tumor.
IDH-mutant gliomas may also show a characteristic ring-enhancement pattern, where the outer edge of the tumor appears brighter on contrast-enhanced imaging.
MRI, and other imaging modalities may be used to diagnose and monitor IDH-mutant gliomas, including computed tomography (CT) scans and positron emission tomography (PET) scans.
Imaging alone cannot definitively diagnose IDH-mutant gliomas.
MRI, whose main functions has been to detect a tumor, provides spatial information for neurosurgical and radiotherapy planning, and to monitor treatment response.
MRI has shown potential in assessing molecular features of gliomas from image-based biomarkers.
T2/FLAIR mismatch sign can identify IDH-mutant, 1p/19q non-codeleted astrocytomas with a specificity of up to 100%.
Multiparametric MRI achieves the highest accuracy in predicting molecular markers.
Isocitrate dehydrogenase mutation is related to more frequency of cortical involvement compared to isocitrate dehydrogenase-wild-type group.
Peritumoral edema is less frequent in isocitrate dehydrogenase-mutant tumors vs for isocitrate dehydrogenase-wild-type tumors.
Isocitrate dehydrogenase-wild-type tumors were more likely to have a nondefinable border, while isocitrate dehydrogenase-mutant tumors had well-defined borders.
Only 17.4% of 46 isocitrate dehydrogenase-mutant tumors demonstrated marked enhancement, while this was 66.7% in isocitrate-wild-type tumors.
Choline-creatinine ratio for isocitrate dehydrogenase-wild-type tumors was significantly higher than that for isocitrate dehydrogenase-mutant tumors.
Frontal location, well-defined border, cortical involvement, less peritumoral edema, lack of enhancement, and low choline-creatinine ratio were predictive for isocitrate dehydrogenase-mutant low-grade gliomas.
IDH wild-type Grade II diffuse gliomas (DGs) are associated with a poor clinical outcome.
The level of evidence for adjuvant treatment of diffuse WHO grade II glioma (low-grade glioma, LGG) is low.
With high risk low-grade glioma most centers use aggressive adjuvant therapy after surgery.
Both radiotherapy and alkylator based chemotherapy help control such tumors, but convey substantial, permanent, toxic effects: therefore, sometimes a watching weight strategy is used as the initial approach.
In a study of 144 patients 40 patients (27.8%) received adjuvant treatment.
The median follow-up duration was 6 years, and the median overall PFS was 3.9 years and OS 16.1 years.
PFS and OS were significantly longer without adjuvant treatment.
A significant difference in favor of no adjuvant therapy was observed even in high-risk patients (age ≥ 40 years or residual tumor, 3.9 vs 3.1 years.
This effect was most pronounced if RT+CT was applied.
In this series of IDH-mutated LGGs, adjuvant treatment with RT, CT with temozolomide (TMZ), or the combination of both showed no significant advantage in terms of PFS and OS.
Even in high-risk patients, the authors observed a similar significantly negative impact of adjuvant treatment on PFS and OS.
In a double-blind, phase 3 trial, of randomly assigned patients with residual or recurrent grade 2 glioma IDH-mutant glioma who had undergone no previous treatment other than surgery to receive either oral vorasidenib (40 mg once daily) or matched placebo in 28-day cycles.
The primary end point was imaging-based progression-free survival.
Progression-free survival was significantly improved in the vorasidenib group as compared with the placebowith progression-free survival, 27.7 months vs. 11.1 months; hazard ratio for disease progression or death.
In patients with grade 2 IDH-mutant glioma, vorasidenib significantly improved progression-free survival and delayed the time to the next intervention.