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Title:
The prognostic significance of CDKN2A homozygous deletion in IDH-mutant lower-grade glioma and glioblastoma: a systematic review of the contemporary literature | Journal of Neuro-Oncology
Description:
Background The most recent cIMPACT-NOW update highlighted the homozygous deletion of the Cyclin Dependent Kinase Inhibitor 2A (CDKN2A) gene as a clinically important molecular alteration in IDH-mutant glioma. Correspondingly, we systematically reviewed the contemporary literature to affirm the contemporary stance of the literature on the prognostic significance of this alteration in this setting based on the current World Health Organization (WHO) Grade classification. Methods A systematic search of seven electronic databases from inception to February 2020 was conducted following PRISMA guidelines. Articles were screened against pre-specified criteria to include lower-grade glioma (LGG, WHO Grade II/III) and glioblastoma (GBM, WHO Grade IV) separately. Progression free survival (PFS) and overall survival (OS) from KaplanâMeier and multivariable analyses were outcomes of interest. Results Nine institutional studies describing 2193 IDH-mutant gliomas satisfied criteria for evaluation, with 1756 (80%) LGG and 437 (20%) GBM. When reported, the proportion of CDKN2A homozygous deleted gliomas ranged from 9 to 43%, with a median incidence of 22%. For LGG, KaplanâMeier analyses demonstrated shorter PFS in the presence of CDKN2A homozygous deletion in three studies (median values, 31 versus 91 months), and shorter OS in five studies (median values, 61 versus 154 months). For GBM, KaplanâMeier analyses demonstrated shorter PFS in the presence of CDKN2A homozygous deletion in two studies (median values, 16 versus 30 months), and shorter OS in four studies (median values, 38 versus 86 months). By multivariable analyses, CDKN2A homozygous deletion was a predictor of significantly shorter PFS and OS in both LGG and GBM across all included studies. Conclusions The CDKN2A homozygous deletion is an important prognostic factor for survival outcomes of IDH-mutant glioma patients across multiple histologic WHO grades with specific molecular features likely dependent on IDH-mutant status. Greater understanding of how identifying this deletion can assist in the stratification of management for these tumors to optimize clinical course is required.
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pubmed, article, google, scholar, central, cas, cdkna, idhmutant, homozygous, deletion, glioma, prognostic, gliomas, neuropathol, survival, studies, health, access, cancer, httpsdoiorgs, content, lowergrade, glioblastoma, grade, acta, van, zhang, privacy, cookies, data, journal, search, systematic, review, literature, iiiii, median, shorter, values, clinical, prognosis, neuro, oncol, perry, deimling, number, information, publish, research, significance,
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idh-mutant lower-grade glioma month download article/chapter targeted rna-sequencing assays diffuse lower-grade gliomas idh-mutant glioma patients idh-mutant astrocytic gliomas include lower-grade glioma central nervous system idh-linked epigenetic perturbation idh mutation status full article pdf grades ii/iii related subjects grade ii/iii idh-mutant status neuro-oncology article idh-mutant glioma reis gf cimino pj copy number alterations tert promoter mutation privacy choices/manage cookies idh-mutant astrocytoma idh-mutant glioblastomas multiple histologic idh-mutant astrocytomas significantly shorter pfs high-grade glioma brat dj recommended grading criteria van den bent specific molecular features award number ul1tr002736 improved grading system newly diagnosed glioblastomas article journal louis dn jackson health system cdh13 promoter methylation cdkn2a homozygous deletion newcastle-ottawa scale important prognostic factor article lu glioma groups based specific surrogate marker kaplanâmeier integrated molecular characterization van thuijl hf article log human cdkn2a locus
Questions {â}
- Tachon G, Cortes U, Richard S, Martin S, Milin S, Evrard C, Lamour C, Karayan-Tapon L (2019) Targeted RNA-sequencing assays: a step forward compared to FISH and IHC techniques?
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headline:The prognostic significance of CDKN2A homozygous deletion in IDH-mutant lower-grade glioma and glioblastoma: a systematic review of the contemporary literature
description:The most recent cIMPACT-NOW update highlighted the homozygous deletion of the Cyclin Dependent Kinase Inhibitor 2A (CDKN2A) gene as a clinically important molecular alteration in IDH-mutant glioma. Correspondingly, we systematically reviewed the contemporary literature to affirm the contemporary stance of the literature on the prognostic significance of this alteration in this setting based on the current World Health Organization (WHO) Grade classification. A systematic search of seven electronic databases from inception to February 2020 was conducted following PRISMA guidelines. Articles were screened against pre-specified criteria to include lower-grade glioma (LGG, WHO Grade II/III) and glioblastoma (GBM, WHO Grade IV) separately. Progression free survival (PFS) and overall survival (OS) from KaplanâMeier and multivariable analyses were outcomes of interest. Nine institutional studies describing 2193 IDH-mutant gliomas satisfied criteria for evaluation, with 1756 (80%) LGG and 437 (20%) GBM. When reported, the proportion of CDKN2A homozygous deleted gliomas ranged from 9 to 43%, with a median incidence of 22%. For LGG, KaplanâMeier analyses demonstrated shorter PFS in the presence of CDKN2A homozygous deletion in three studies (median values, 31 versus 91Â months), and shorter OS in five studies (median values, 61 versus 154Â months). For GBM, KaplanâMeier analyses demonstrated shorter PFS in the presence of CDKN2A homozygous deletion in two studies (median values, 16 versus 30Â months), and shorter OS in four studies (median values, 38 versus 86Â months). By multivariable analyses, CDKN2A homozygous deletion was a predictor of significantly shorter PFS and OS in both LGG and GBM across all included studies. The CDKN2A homozygous deletion is an important prognostic factor for survival outcomes of IDH-mutant glioma patients across multiple histologic WHO grades with specific molecular features likely dependent on IDH-mutant status. Greater understanding of how identifying this deletion can assist in the stratification of management for these tumors to optimize clinical course is required.
datePublished:2020-05-08T00:00:00Z
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CDKN2A
Deletion
Glioma
Glioblastoma
Cyclin
Prognosis
Survival
Oncology
Neurology
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headline:The prognostic significance of CDKN2A homozygous deletion in IDH-mutant lower-grade glioma and glioblastoma: a systematic review of the contemporary literature
description:The most recent cIMPACT-NOW update highlighted the homozygous deletion of the Cyclin Dependent Kinase Inhibitor 2A (CDKN2A) gene as a clinically important molecular alteration in IDH-mutant glioma. Correspondingly, we systematically reviewed the contemporary literature to affirm the contemporary stance of the literature on the prognostic significance of this alteration in this setting based on the current World Health Organization (WHO) Grade classification. A systematic search of seven electronic databases from inception to February 2020 was conducted following PRISMA guidelines. Articles were screened against pre-specified criteria to include lower-grade glioma (LGG, WHO Grade II/III) and glioblastoma (GBM, WHO Grade IV) separately. Progression free survival (PFS) and overall survival (OS) from KaplanâMeier and multivariable analyses were outcomes of interest. Nine institutional studies describing 2193 IDH-mutant gliomas satisfied criteria for evaluation, with 1756 (80%) LGG and 437 (20%) GBM. When reported, the proportion of CDKN2A homozygous deleted gliomas ranged from 9 to 43%, with a median incidence of 22%. For LGG, KaplanâMeier analyses demonstrated shorter PFS in the presence of CDKN2A homozygous deletion in three studies (median values, 31 versus 91Â months), and shorter OS in five studies (median values, 61 versus 154Â months). For GBM, KaplanâMeier analyses demonstrated shorter PFS in the presence of CDKN2A homozygous deletion in two studies (median values, 16 versus 30Â months), and shorter OS in four studies (median values, 38 versus 86Â months). By multivariable analyses, CDKN2A homozygous deletion was a predictor of significantly shorter PFS and OS in both LGG and GBM across all included studies. The CDKN2A homozygous deletion is an important prognostic factor for survival outcomes of IDH-mutant glioma patients across multiple histologic WHO grades with specific molecular features likely dependent on IDH-mutant status. Greater understanding of how identifying this deletion can assist in the stratification of management for these tumors to optimize clinical course is required.
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CDKN2A
Deletion
Glioma
Glioblastoma
Cyclin
Prognosis
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Neurology
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