Isocitrate Dehydrogenase Mutations in Low-Grade Gliomas Correlate With Prolonged Overall Survival in Older Patients.


Journal

Neurosurgery
ISSN: 1524-4040
Titre abrégé: Neurosurgery
Pays: United States
ID NLM: 7802914

Informations de publication

Date de publication:
01 02 2019
Historique:
received: 21 09 2017
accepted: 25 03 2018
pubmed: 31 5 2018
medline: 1 1 2020
entrez: 31 5 2018
Statut: ppublish

Résumé

Older age has been associated with worse outcomes in low-grade gliomas (LGGs). Given their rarity in the older population, determining optimal treatment plans and patient outcomes remains difficult. To retrospectively study LGG survival outcomes in an older population stratified by molecular genetic profiles. We included patients age ≥40 yr with pathologically confirmed World Health Organization grade II gliomas treated at a single institution between 1995 and 2015. We collected tumor genomic information when available. Median overall survival for the entire group (n = 111, median age 51 yr, range 40-77 yr) was 15.75 yr with 5- and 10-yr survival rates of 84.3% and 67.7%, respectively. On univariate analysis, patients with isocitrate dehydrogenase (IDH) mutation had significantly increased survival compared to IDH wildtype (hazard ratio [HR] 0.17 [0.07-0.45], P < .001). Older age, seizure at presentation, larger tumor size, IDH wildtype, biopsy only, chemotherapy, and radiation were significantly associated with shorter survival based on univariate analyses. In patients with known IDH status (n = 73), bivariate analysis of IDH mutation status and age showed only IDH status significantly influenced overall survival (HR 0.22 [0.07-0.68], P = .008). Greater surgical resection was predictive of survival, although extent of resection significantly correlated with IDH mutation status (odds ratio 7.5; P < .001). We show that genomic alterations in LGG patients ≥40 occur at high rates like the younger population and predict a similar survival advantage. Maximizing surgical resection may have survival benefit, although feasibility of resection is often linked to IDH status. Given the importance of molecular genetics, a redefinition of prognostic factors associated with these tumors is likely to emerge.

Sections du résumé

BACKGROUND
Older age has been associated with worse outcomes in low-grade gliomas (LGGs). Given their rarity in the older population, determining optimal treatment plans and patient outcomes remains difficult.
OBJECTIVE
To retrospectively study LGG survival outcomes in an older population stratified by molecular genetic profiles.
METHODS
We included patients age ≥40 yr with pathologically confirmed World Health Organization grade II gliomas treated at a single institution between 1995 and 2015. We collected tumor genomic information when available.
RESULTS
Median overall survival for the entire group (n = 111, median age 51 yr, range 40-77 yr) was 15.75 yr with 5- and 10-yr survival rates of 84.3% and 67.7%, respectively. On univariate analysis, patients with isocitrate dehydrogenase (IDH) mutation had significantly increased survival compared to IDH wildtype (hazard ratio [HR] 0.17 [0.07-0.45], P < .001). Older age, seizure at presentation, larger tumor size, IDH wildtype, biopsy only, chemotherapy, and radiation were significantly associated with shorter survival based on univariate analyses. In patients with known IDH status (n = 73), bivariate analysis of IDH mutation status and age showed only IDH status significantly influenced overall survival (HR 0.22 [0.07-0.68], P = .008). Greater surgical resection was predictive of survival, although extent of resection significantly correlated with IDH mutation status (odds ratio 7.5; P < .001).
CONCLUSION
We show that genomic alterations in LGG patients ≥40 occur at high rates like the younger population and predict a similar survival advantage. Maximizing surgical resection may have survival benefit, although feasibility of resection is often linked to IDH status. Given the importance of molecular genetics, a redefinition of prognostic factors associated with these tumors is likely to emerge.

Identifiants

pubmed: 29846690
pii: 5004649
doi: 10.1093/neuros/nyy149
doi:

Substances chimiques

Isocitrate Dehydrogenase EC 1.1.1.41

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

519-528

Auteurs

Pamela S Jones (PS)

Department of Neurosurgery, Massachusetts General Hospital, Boston, Massachusetts.

Kate T Carroll (KT)

School of Medicine, University of California-San Diego, San Diego, California.

Matthew Koch (M)

Department of Neurosurgery, Massachusetts General Hospital, Boston, Massachusetts.

Jasmine A T DiCesare (JAT)

Department of Neurosurgery, University of California-Los Angeles, Los Angeles, California.

Kara Reitz (K)

Department of Neurosurgery, Massachusetts General Hospital, Boston, Massachusetts.

Matthew Frosch (M)

Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts.

Fred G Barker (FG)

Department of Neurosurgery, Massachusetts General Hospital, Boston, Massachusetts.

Daniel P Cahill (DP)

Department of Neurosurgery, Massachusetts General Hospital, Boston, Massachusetts.

William T Curry (WT)

Department of Neurosurgery, Massachusetts General Hospital, Boston, Massachusetts.

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