IDH wild-type lower-grade gliomas with glioblastoma molecular features: a systematic review and meta-analysis

Nakasu, Satoshi; Deguchi, Shoichi; Nakasu, Yoko

doi:10.1007/s10014-023-00463-8

Cited by 6 publications

(2 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This could make a complete difference when it comes to survival profiles since grade 4 astrocytomas are tumors with better prognostic factors than GBMs [ 10 , 38 , 39 , 40 ]. In our study, for example, the aggressiveness of these types of tumors can be seen when we observe that, after the follow-up period up to November 2023, only 12.8% of the 78 patients were alive.…”

Section: Discussionmentioning

confidence: 99%

Pyrosequencing Analysis of O-6-Methylguanine-DNA Methyltransferase Methylation at Different Cut-Offs of Positivity Associated with Treatment Response and Disease-Specific Survival in Isocitrate Dehydrogenase-Wildtype Grade 4 Glioblastoma

Silva,

Di Domenico,

Caponio

et al. 2024

IJMS

View full text Add to dashboard Cite

The O-6-methylguanine-DNA methyltransferase (MGMT) gene is a critical guardian of genomic integrity. MGMT methylation in diffuse gliomas serves as an important determinant of patients’ prognostic outcomes, more specifically in glioblastomas (GBMs). In GBMs, the absence of MGMT methylation, known as MGMT promoter unmethylation, often translates into a more challenging clinical scenario, tending to present resistance to chemotherapy and a worse prognosis. A pyrosequencing (PSQ) technique was used to analyze MGMT methylation status at different cut-offs (5%, 9%, and 11%) in a sample of 78 patients diagnosed with IDH-wildtype grade 4 GBM. A retrospective analysis was provided to collect clinicopathological and prognostic data. A statistical analysis was used to establish an association between methylation status and treatment response (TR) and disease-specific survival (DSS). The patients with methylated MGMT status experienced progressive disease rates of 84.6%, 80%, and 78.4% at the respective cut-offs of 5%, 9%, and 11%. The number was considerably higher when considering unmethylated patients, as all patients (100%), regardless of the cut-off, presented progressive disease. Regarding disease-specific survival (DSS), the Hazard Ratio (HR) was HR = 0.74 (0.45–1.24; p = 0.251); HR = 0.82 (0.51–1.33; p = 0.425); and HR = 0.79 (0.49–1.29; p = 0.350), respectively. Our study concludes that there is an association between MGMT unmethylation and worse TR and DSS. The 9% cut-off demonstrated a greater potential for patient survival as a function of time, which may shed light on the future need for standardization of MGMT methylation positivity parameters in PSQ.

show abstract

Section: Discussionmentioning

confidence: 99%

Pyrosequencing Analysis of O-6-Methylguanine-DNA Methyltransferase Methylation at Different Cut-Offs of Positivity Associated with Treatment Response and Disease-Specific Survival in Isocitrate Dehydrogenase-Wildtype Grade 4 Glioblastoma

Silva,

Di Domenico,

Caponio

et al. 2024

IJMS

View full text Add to dashboard Cite

show abstract

“…They found that most patients with IDH-WT grade 2 gliomas met the cIMPACT criteria because of isolated TERT promoter mutations that were not predictive of poor outcomes, hence, some caution is needed when assimilating IDH-WT grade 2 gliomas to molecular glioblastomas, especially those with isolated TERT promoter mutation [15]. A recent metanalysis showed that patients with molecular GBM (presence of TERT promoter mutation, EGFR amplification, or chromosome seven gain and ten loss aberrations) had significantly longer OS times when compared to histological GBM (pooled hazard ratio 0.824, [CI: 0.694-0.98], p = 0.03)) and histological grade, age, and surgical extent were significant prognostic factors, with grade 2 molecular GBM showing better OS rates when compared to histological GBM [16].…”

Section: Introductionmentioning

confidence: 99%

Isocitrate Dehydrogenase 1/2 Wildtype Adult Astrocytoma with WHO Grade 2/3 Histological Features: Molecular Re-Classification, Prognostic Factors, Clinical Outcomes

Gupta,

Anjari,

Brandner

et al. 2024

Biomedicines

View full text Add to dashboard Cite

Background: Isocitrate Dehydrogenase 1/2 (IDH 1/2)-wildtype (WT) astrocytomas constitute a heterogeneous group of tumors and have undergone a series of diagnostic reclassifications over time. This study aimed to investigate molecular markers, clinical, imaging, and treatment factors predictive of outcomes in WHO grade 2/3 IDH-WT astrocytomas (‘early glioblastoma’). Methodology: Patients with WHO grade 2/3 IDH-WT astrocytomas were identified from the hospital archives. They were cross-referenced with the electronic medical records systems, including neuroimaging. The expert neuro-pathology team retrieved data on molecular markers—MGMT, TERT, IDH, and EGFR. Tumors with a TERT mutation and/or EGFR amplification were reclassified as glioblastoma. Results: Fifty-four patients were identified. Sixty-three percent of the patients could be conclusively reclassified as glioblastoma based on either TERT mutation, EGFR amplification, or both. On imaging, 65% showed gadolinium enhancement on MRI. Thirty-nine patients (72%) received long-course radiotherapy, of whom 64% received concurrent chemotherapy. The median follow-up of the group was 16 months (range: 2–90), and the median overall survival (OS) was 17.3 months. The 2-year OS of the whole cohort was 31%. On univariate analysis, older age, worse performance status (PS), and presence versus absence of contrast enhancement on diagnostic MRI were statistically significant for poorer OS. Conclusion: IDH-WT WHO grade 2/3 astrocytomas are a heterogeneous group of tumors with poor clinical outcomes. The majority can be reclassified as glioblastoma, based on current WHO classification criteria, but further understanding of the underlying biology of these tumors and the discovery of novel targeted agents are needed for better outcomes.

show abstract

Patterns of T2-FLAIR discordance across a cohort of adult-type diffuse gliomas and deviations from the classic T2-FLAIR mismatch sign

Malik,

Soliman,

Chen

et al. 2024

Neuroradiology

View full text Add to dashboard Cite

IDH wild-type lower-grade gliomas with glioblastoma molecular features: a systematic review and meta-analysis

Cited by 6 publications

References 65 publications

Pyrosequencing Analysis of O-6-Methylguanine-DNA Methyltransferase Methylation at Different Cut-Offs of Positivity Associated with Treatment Response and Disease-Specific Survival in Isocitrate Dehydrogenase-Wildtype Grade 4 Glioblastoma

Pyrosequencing Analysis of O-6-Methylguanine-DNA Methyltransferase Methylation at Different Cut-Offs of Positivity Associated with Treatment Response and Disease-Specific Survival in Isocitrate Dehydrogenase-Wildtype Grade 4 Glioblastoma

Isocitrate Dehydrogenase 1/2 Wildtype Adult Astrocytoma with WHO Grade 2/3 Histological Features: Molecular Re-Classification, Prognostic Factors, Clinical Outcomes

Patterns of T2-FLAIR discordance across a cohort of adult-type diffuse gliomas and deviations from the classic T2-FLAIR mismatch sign

Contact Info

Product

Resources

About