• Journal of Korean Neurosurgical Society
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• 제66권4호
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• pp.465-475
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• 2023

Objective : Our objective is to analyze the occurrence, clinical course and risk factors for glioma patients with leptomeningeal metastasis (LM) according to different metastasis patterns and clinical variables. Methods : We retrospectively reviewed data from 376 World Health Organization (WHO) grade II-IV adult glioma patients who were treated in the National Cancer Center from 2001 to 2020. Patients who underwent surgery at other institutions, those without initial images or those with pathologically unconfirmed cases were excluded. LM was diagnosed based on magnetic resonance imaging (MRI) findings or cerebrospinal fluid (CSF) cytology. The metastasis pattern was categorized as nodular or linear according to the enhancement pattern. Tumor proximity to the CSF space was classified as involved or separated, whereas location of the tumor was dichotomized as midline, for tumors residing in the thalamus, basal ganglia and brainstem, or lateral, for tumors residing in the cerebral and cerebellar hemispheres. Results : A total of 138 patients were enrolled in the study. A total of 44 patients (38%) were diagnosed with LM during a median follow-up of 9 months (range, 0-60). Among the clinical variables, tumor proximity to CSF space, the location of the tumor and the WHO grade were significant factors for LM development in univariate analysis. In multivariate analysis, the midline location of the tumor and WHO grade IV gliomas were the most significant factor for LM development. The hazard ratio was 2.624 for midline located gliomas (95% confidence interval [CI], 1.384-4.974; p=0.003) and 3.008 for WHO grade IV gliomas (95% CI, 1.379-6.561; p=0.006). Conclusion : Midline location and histological grading are an important factor for LM in glioma patients. The proximity to the CSF circulation pathway is also an important factor for WHO grade IV glioma LM. Patients carrying high risks should be followed up more thoroughly.

• Korean Journal of Radiology
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• 제24권8호
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• pp.772-783
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• 2023

Objective: Imaging-based survival stratification of patients with gliomas is important for their management, and the 2021 WHO classification system must be clinically tested. The aim of this study was to compare integrative imaging- and pathology-based methods for survival stratification of patients with diffuse glioma. Materials and Methods: This study included diffuse glioma cases from The Cancer Genome Atlas (training set: 141 patients) and Asan Medical Center (validation set: 131 patients). Two neuroradiologists analyzed presurgical CT and MRI to assign gliomas to five imaging-based risk subgroups (1 to 5) according to well-known imaging phenotypes (e.g., T2/FLAIR mismatch) and recategorized them into three imaging-based risk groups, according to the 2021 WHO classification: group 1 (corresponding to risk subgroup 1, indicating oligodendroglioma, isocitrate dehydrogenase [IDH]-mutant, and 1p19q-codeleted), group 2 (risk subgroups 2 and 3, indicating astrocytoma, IDH-mutant), and group 3 (risk subgroups 4 and 5, indicating glioblastoma, IDHwt). The progression-free survival (PFS) and overall survival (OS) were estimated for each imaging risk group, subgroup, and pathological diagnosis. Time-dependent area-under-the receiver operating characteristic analysis (AUC) was used to compare the performance between imaging-based and pathology-based survival model. Results: Both OS and PFS were stratified according to the five imaging-based risk subgroups (P < 0.001) and three imaging-based risk groups (P < 0.001). The three imaging-based groups showed high performance in predicting PFS at one-year (AUC, 0.787) and five-years (AUC, 0.823), which was similar to that of the pathology-based prediction of PFS (AUC of 0.785 and 0.837). Combined with clinical predictors, the performance of the imaging-based survival model for 1- and 3-year PFS (AUC 0.813 and 0.921) was similar to that of the pathology-based survival model (AUC 0.839 and 0.889). Conclusion: Imaging-based survival stratification according to the 2021 WHO classification demonstrated a performance similar to that of pathology-based survival stratification, especially in predicting PFS.

• Asian Pacific Journal of Cancer Prevention
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• 제14권1호
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• pp.449-452
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• 2013

Polymorphisms in DNA repair genes have been shown to influence DNA repair processes and to modify cancer susceptibility. Here we conducted a case-control study to assess the role of potential SNPs of DNA repair genes on the risk of glioma and meningioma. We included 297 cases and 458 cancer-free controls. Genotyping of XRCC1 Gln399Arg, XRCC1 Arg194Trp, XRCC2 Arg188His, XRCC3 Thr241Met, XRCC4 Ala247Ser, ERCC1 Asn118Asp, ERCC2 Lys751Gln and ERCC5 Asp1558His were performed in a 384-well plate format on the Sequenom MassARRAY platform. XRCC1 Arg194Trp (rs1799782) and ERCC2 Asp312Asn rs1799793 did not follow the HWE in control group, and genotype distributions of XRCC1 Gln399Arg rs25487, XRCC2 Arg188His rs3218536 and ERCC2 Asp312Asn rs1799793 were significantly different between cases and controls (P<0.05). We found XRCC1 399G/G, XRCC1 194 T/T and XRCC3 241T/T were associated with a higher risk when compared with the wild-type genotype. For ERCC5 Asp1558His, we found G/G genotype was associated with elevated susceptibility. In conclusion, our study has shown that XRCC1 Gln399Arg, XRCC1 Arg194Trp, XRCC3 Thr241Met and ERCC5 Asp1558His are associated with risk of gliomas and meningiomas. This finding could be useful in identifying the susceptibility genes for these cancers.

• Asian Pacific Journal of Cancer Prevention
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• 제13권6호
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• pp.2791-2794
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• 2012

Aims: We conducted a case-control study in a Chinese population to clarify the association between polymorphisms in ERCC1 and XPD and susceptibility and survival of glioma. Methods: A total of 393 cases and 410 controls were selected from March 2007 to December 2011. Genotyping of ERCC1 and XPD was conducted by TaqMan assays using the ABI Prism 7911HT Sequence Detection System. All analyses were performed using the STATA statistical package. Results: Polymorphisms in ERCC1 118C/T, ERCC1 8092C/A and XPD Asp312Asn showed no statistically significant difference between glioma cases and controls. However, individuals with the XPD 751Gln/Gln genotype had an increased risk of developing glioma compared with those with the Lys/Lys genotype (adjusted OR=1.64, 95% CI: 1.06-2.89). The ERCC1 118T/T genotype was associated with significantly higher median survival than the ERCC1 C/C genotype (HR=0.67, 95%CI=0.35-0.96). In addition, individuals with XPD 751Gln/Gln had a lower median survival time than XPD Lys/Lys carriers (HR=0.54, 95%CI=0.37-0.93). Conclusion: In conclusion, we observed that the XPD 751Gln/Gln genotype is associated with glioma susceptibility, and ERCC1 118 T/T and XPD 751Gln/Gln genotypes confer a significantly better prognosis.

• Journal of Korean Neurosurgical Society
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• 제41권6호
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• pp.387-390
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• 2007

Objective : To determine the presentation, incidence, and risk factors of seizures in patients treated for brain tumors. Methods : One hundred patients who consecutively underwent a craniotomy for the treatment of supratentorial brain tumors were assessed. The pathologies of the patients enrolled in the study included glioma [n=56], meningioma [n=31], metastatic brain tumor [n=7], primary central nervous system lymphoma [n=4], and central neurocytoma [n=2]. Anti-epileptic drugs [AEDs] were administered to all patients for up to six months after the surgery. Pre-defined variables for outcome analysis included tumor grade and location, extent of tumor resection, number of seizures, age at tumor diagnosis, adjuvant therapy, medication and radiological abnormalities. Results : Thirty patients [30%] presented at least a single episode of seizure at the time of admission. Five of these patients [16.7%] developed the seizure during the follow-up period. Newly developed seizure was noticed in six out of seventy patients [8.6%] without prior seizure. Histopathology was malignant gliomas in 10 and supratentorial meningioma in one. Early seizure developed only in two patients. Conclusion : Compared with patients without seizure, patients with seizure at the time of admission showed younger age [p=0.003], a higher portion of low-grade glioma [p=0.001], tumor location in the frontal and temporal lobes [p=0.003] and cortical involvement [p=0.017]. Our study suggestes that tumor progression is considered a significant risk factor for seizure development in glioma patients.

• Asian Pacific Journal of Cancer Prevention
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• 제14권12호
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• pp.7261-7264
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• 2013

Recent genome wide sequencing has identified mutations in IDH1/IDH2 predominantly in grade II-III gliomas and secondary glioblastomas which are associated with favorable clinical outcome. These mutations have become molecular markers of significant diagnostic and prognostic relevance in the assessment of human gliomas. In the current study we evaluated IDH1 (R132) and IDH2 (R172) in 32 gliomas of various grades and tumor subtypes. Sequencing analysis revealed R132H mutations in 18.7% tumors, while none of the cases showed IDH2 (R172) mutations. The frequency of IDH1 mutations was higher in females (21.4%) than males (11.1%), and it was significantly higher in younger patients. Histological analyses demonstrated presence of necrosis and micro vascular proliferation in 69% and 75% respectively. Interestingly, IDH1 mutations were predominantly present in non-necrotic tumors as well as in cases showing microvascular proliferation. Of the six IDH1 positive cases, three were glioblastomas (IV), and one each were anaplastic oligoastrocytoma (III), anaplastic oligodendroglioma III (n=1) and diffuse astrocytoma. In conclusion, IDH1 mutations are quite frequent in Indian glioma patients while IDH2 mutations are not observed. Since IDH mutations are associated with good prognosis, their use in routine clinical practice will enable better risk stratification and management of glioma patients.

• Asian Pacific Journal of Cancer Prevention
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• 제13권1호
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• pp.157-163
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• 2012

Objective: Glutathione S-transferases (GSTs) are multifunctional enzymes that play a crucial role in the detoxification of both the endogenous products of oxidative stress and exogenous carcinogens. Recent studies investigating the association between genetic polymorphisms in GSTs and the risk of adult brain tumors have reported conflicting results. The rationale of this pooled analysis was to determine whether the presence of a GST variant increases adult glioma susceptibility by combining data from multiple studies. Methods: In our meta-analysis, 12 studies were identified by a search of the MEDLINE, HIGHWIRE, SCIENCEDIRECT and EMBASE databases. Of those 12, 11 evaluated GSTM1, nine evaluated GSTT1 and seven evaluated GSTP1 Ile105Val. Between-study heterogeneity was assessed using ${\chi}^2$-based Q statistic and the $I^2$ statistic. Crude odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were used to estimate the association between GSTM1, GSTT1 and GSTP1 polymorphisms and the risk of adult gliomas. Results: The quantitative synthesis showed no significant evidence to indicate an association exists between the presence of a GSTM1, GSTT1 or GSTP1 Ile105Val haplotype polymorphism and the risk of adult gliomas (OR, 1.008, 1.246, 1.061 respectively; 95% CI, 0.901-1.129, 0.963-1.611, 0.653-1.724 respectively). Conclusions: Overall, this study did not suggest any strong relationship between GST variants or related enzyme polymorphisms and an increased risk of adult gliomas. Some caveats include absence of specific raw information on ethnic groups or smoking history on glioma cases in published articles; therefore, well-designed studies with a clear stratified analysis on potential confounding factors are needed to confirm these results.

• Journal of Korean Neurosurgical Society
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• 제66권5호
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• pp.562-572
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• 2023

Objective : Bevacizumab is a feasible option for treating cerebral radiation necrosis (RN). We investigated the clinical outcome of RN after treatment with bevacizumab and factors related to the initial response and the sustained effect. Methods : Clinical data of 45 patients treated for symptomatic RN between September 2019 and February 2021 were retrospectively collected. Bevacizumab (7.5 mg/kg) was administered at 3-week intervals with a maximum four-cycle schedule. Changes in the lesions magnetic resonance image (MRI) scans were examined for the response evaluation. The subgroup analysis was performed based on the initial response and the long-term maintenance of the effect. Results : Of the 45 patients, 36 patients (80.0%) showed an initial response, and eight patients (17.8%) showed delayed worsening of the corresponding lesion. The non-responders showed a significantly higher incidence of diffusion restriction on MRI than the responders (100.0% vs. 25.0%, p<0.001). The delayed worsening group showed a significantly higher proportion of glioma pathology than the maintenance group (87.5% vs. 28.6%, p=0.005). Cumulative survival rates with sustained effect were significantly higher in the groups with non-glioma pathology (p=0.019) and the absence of diffusion restriction (p<0.001). Pathology of glioma and diffusion restriction in MRI were the independent risk factors for non-response or delayed worsening after initial response. Conclusion : The initial response of RN to bevacizumab was favorable, with improvement in four-fifths of the patients. However, a certain proportion of patients showed non-responsiveness or delayed exacerbations. Bevacizumab may be more effective in treating RN in patients with non-glioma pathology and without diffusion restriction in the MRI.

• Asian Pacific Journal of Cancer Prevention
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• 제15권18호
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• pp.7639-7644
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• 2014

Background: Results from previous studies concerning the association of ERCC4 rs1800067 polymorphism with risk of cancer were inconsistent. To explore the exact relation with susceptibility, we conducted the present meta-analysis. Materials and Methods: Literature of electronic databases including PubMed, Web of Science, EMBASE, Wanfang and Chinese National Knowledge Infrastructure (CNKI) were systematically searched. ORs and their 95%CIs were used to assess the strength of associations between ERCC4 polymorphism and cancer risk. Results: There was no significant association between ERCC4 rs1800067 AA or AG genotypes and overall risk of cancer (AA vs. GG: OR=0.998, 95%CI=0.670-1.486, P=0.992; AG vs. GG: OR=0.970, 95%CI=0.888-1.061, P=0.508). A dominant genetic model also did not demonstrate significant association of (AA+AG) genotype carriers with altered risk of overall cancer (OR=0.985, 95%CI=0.909-1.068, P=0.719). In addition, no significant association was observed between A allele of ERCC4 rs1800067 A/G polymorphism and altered cancer risk compared with G allele (OR=0.952, 95%CI=0.851-1.063, P=0.381). Subgroup analysis suggested that AA genotype carriers were significantly associated with decreased risk of glioma compared with wild-type GG genotype individuals (OR=0.523, 95%CI=0.275-0.993, P=0.048). For subgroup of lung cancer, A allele of ERCC4 rs1800067 A/G polymorphism was significantly associated with decreased risk of lung cancer compared with G allele (OR=0.806, 95%CI=0.697-0.931, P=0.003). Conclusions: This meta-analysis indicated that ERCC4 rs1800067 A/G polymorphism might not be associated with risk of overall cancer. However, individuals with the AA genotype were associated with significantly reduced risk of glioma compared with wild-type GG genotype; The A allele was associated with significantly reduced risk of lung cancer compared with G allele. Future large-scale studies performed in multiple populations are warranted to confirm our results.

• Asian Pacific Journal of Cancer Prevention
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• 제13권9호
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• pp.4783-4788
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• 2012

Objective: Previous studies of the association between X-ray cross-complementing group 1 (XRCC1) gene polymorphisms and the gliomas risk have yielded conflicting results, and thus a meta-analysis was performed to provide a more accurate estimation. Methods: A computerized literature search of 5 electronic databases was conducted to identify the relevant studies. Fixed or random effect models were selected based on the heterogeneity test. Publication bias was estimated using Begg's funnel plots and Egger's regression test. Results: A total of 11 studies (3,810 cases and 6,079 controls), 7 studies (2,928 cases and 5,048 controls), and 4 studies (1,461 cases and 2,593 controls) were finally included in the analyses of the association between XRCC1 Arg399Gln, Arg194Trp, and Arg280His polymorphisms and glioma risk, respectively. The pooled results showed that GlnGln carriage was associated with moderately increased risk of gliomas in Asians (GlnGln vs. ArgArg, OR=1.490, 95%CI 1.031-2.153; GlnGln/ArgGln vs. ArgArg, OR=1.321, 95%CI 1.037-1.684), whereas a marginal association was revealed in Caucasians. For the Arg194Trp polymorphism, although a significant association was shown in the homozygous genotype comparisons (TrpTrp vs. ArgArg, OR = 2.209, 95%CI 1.398-2.945), no significant link was found on subgroup analysis stratified by ethnicity. With regard to the Arg280His polymorphism, no significant association was found in each comparison. No particular study was found to significantly influence the pooled results, and no potential publication bias was detected. Conclusions: This meta-analysis suggested that the XRCC1 Arg399Gln polymorphism is moderately associated with increased risk of gliomas in Asians, while Arg194Trp and Arg280His polymorphisms demonstrated no significant influence. Due to the limited studies and the potential confounders, further studies are needed to confirm these results.