Combined IDH1 mutation and MGMT methylation status on long-term survival of patients with cerebral low-grade glioma.
OBJECTIVE
The management of low-grade glioma (LGG) still remains controversial because the effectiveness of early and extensive resection is unclear, and the use of radiation therapy or chemotherapy is not well-defined. In particular, the importance of prognostic factors for survival remains a matter of discussion. The purpose of this study was to validate prognostic factors for survival in patients with LGG.


METHODS
A consecutive series of 55 patients with WHO grade II LGG treated in our institute between 1983 and 2013 were retrospectively reviewed to determine the prognostic factors for survival. All data were retrospectively analyzed from the aspect of baseline characteristics, pathological findings, genetic change, surgical treatments, adjuvant therapies, and survival time. Cox multivariate analysis was performed to determine the prognostic factors for survival.


RESULTS
There were 28 patients with diffuse astrocytoma (DA), 21 patients with oligodendroglioma (OG), and 6 patients with oligoastrocytoma (OA) diagnosed on initial surgery. The median overall survival was 193 months and fifteen patients (27.3%) died. A mutation in isocitrate dehydrogenase-1 (IDH1) was found in 72.9% of LGG, and this mutation was positively correlated with methylation of O6-methylguanine-DNA methyltransferase (MGMT) (p=0.02). A better prognosis was significantly associated with combined IDH1 mutation and MGMT methylation status (both positive vs both negative, HR 0.079 [95% CI 0.008-0.579], p=0.012), as well as histology (OG vs DA and OA, HR 0.158 [95% CI 0.022-0.674], p=0.011) and tumor size (<6 cm vs ≥6 cm, HR 0.120 [95% CI 0.017-0.595], p=0.008).


CONCLUSIONS
Tumor histology, size and IDH-mutation status are important predictors for prolonged overall survival in patients with LGG and may provide a reliable tool for standardizing future treatment strategies.
Department of Neurosurgery, Kobe University Graduate School of Medicine, Kobe, Japan. Electronic address: kazutana@med.kobe-u.ac.jp.
Kazuhiro
K
Tanaka
Department of Neurosurgery, Kobe University Graduate School of Medicine, Kobe, Japan.
Takashi
T
Sasayama
Department of Neurosurgery, Kobe University Graduate School of Medicine, Kobe, Japan.
Katsu
K
Mizukawa
Department of Neurosurgery, Kobe University Graduate School of Medicine, Kobe, Japan.
Kumi
K
Takata
Department of Radiation Oncology, Kobe University Graduate School of Medicine, Kobe, Japan.
Nor Shazrina
NS
Sulaiman
Department of Neurosurgery, Kobe University Graduate School of Medicine, Kobe, Japan.
Masamitsu
M
Nishihara
Department of Neurosurgery, Kobe University Graduate School of Medicine, Kobe, Japan.
Masaaki
M
Kohta
Department of Radiation Oncology, Kobe University Graduate School of Medicine, Kobe, Japan.
Ryohei
R
Sasaki
Department of Pathology for Regional Communication, Kobe University Graduate School of Medicine, Kobe, Japan.
Takanori
T
Hirose
Department of Diagnostic Pathology, Kobe University Graduate School of Medicine, Kobe, Japan.
Tomoo
T
Itoh
Department of Neurosurgery, Kobe University Graduate School of Medicine, Kobe, Japan.
Eiji
E
Kohmura
D000293:Adolescent; D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D003131:Combined Modality Therapy; D005260:Female; D020022:Genetic Predisposition to Disease; D005910:Glioma / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D012189:Retrospective Studies; D055815:Young Adult
D007521:Isocitrate Dehydrogenase; D019853:O(6)-Methylguanine-DNA Methyltransferase
IDH1 mutation; Low grade glioma; MGMT methylation; Prognostic factor