• Asian Pacific Journal of Cancer Prevention
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• v.15 no.3
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• pp.1333-1337
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• 2014

Background: Astrocytic tumors, the most common primary glial tumors of the central nervous system, are classified from low to high grade according to the degree of anaplasia and presence of necrosis. Despite advances in therapeutic management of high grade astrocytic tumors, prognosis remains poor. In the present study, the frequency and prognostic significance of c-erb-B2 in astrocytic tumors was investigated. Materials and Methods: Records of 72 patients with low- and high-grade astrocytic tumors were evaluated. The expression of C-erbB-2 was determined immunohistochemically and intensity was recorded as 0 to 3+. Tumors with weak staining (1+) or no staining (0) were considered Her-2 negative, while tumors with moderate (2+) and strong (3+) staining were considered Her-2 positive. Results: Of the 72 patients, 41 (56.9%) had glioblastoma (GBM), 10 (13.9%) had diffuse astrocytoma, 15 (20.8%) had anaplastic astrocytoma, 6 (8.3%) had pilocytic astrocytoma. C-erbB-2 overexpression was detected in the tumor specimens of 17 patients (23.6%). Six (8.3%) tumors, all GBMs, exhibited strong staining, 2 (2.7%) specimens, both GBMs, exhibited moderate staining, and 9 specimens, 5 of them GBMs (12.5%), exhibited weak staining. No staining was observed in diffuse astrocytoma and pilocytic astrocytoma specimens. Median overall survival of patients with C-erbB-2 negative and C-erbB-2 positive tumors were 30 months (95%CI: 22.5-37.4 months) and 16.9 months (95%CI: 4.3-29.5 months), respectively (p=0.244). Conclusions: Although there was no difference in survival, C-erbB-2 overexpression was observed only in the GBM subtype.

• Journal of Korean Neurosurgical Society
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• v.30 no.4
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• pp.430-436
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• 2001

Objective : The proliferative potential of intracranial glioma affects the histological malignancy and prognosis of patients with these tumors. In this study, we present the relationship between MIB-1 labeling index(LI) and clinical variables which might play the major role in determining the prognosis of patient with astrocytic tumors. Patients and Methods : Excised tumor specimens from a total of 52 patients were stained to detect monoclonal MIB-1-Ki-67 antibody by avidin-biotin complex immunohistochemistry. The MIB-1 LI was evaluated with histological grades, demograpghic data, and survival time. The statistical significance of their correlation was analyzed by Pearson correlation test. Results : The 52 patients included 30 male patients and 22 female patients. The tumors according to the criteria of the World Health Organization(WHO) classification were verified as pleomorphic xanthoastrocytoma in one, pilocytic astrocytomas 4, astrocytomas 1, anaplastic astrocytomas 3, and glioblastomas 31. MIB-1 LI in astrocytic ttumors showed no correlation with age and gender. However, the patients under 10 years had the longest survival time, whereas short survival time was observed in the older patients. The mean MIB-1 LI of different tumor grades were as follows : pleomorphic xanthoastrocytoma, $4.40{\pm}0.00$ ; pilocytic astrocytoma, $4.53{\pm}3.09$ ; astrocytoma, $5.50{\pm}6.03$ ; anaplastic astrocytoma, $12.68{\pm}12.50$ ; Glioblastoma, $21.31{\pm}19.63$. Although the levels of MIB-1 LI were varied in individual tumors, the MIB-1 LI was increased in parallel with the histological grades. Glioblstomas showed significantly higher MIB-1 LI compared with that of anaplastic astrocytomas and low grade astrocytomas (p = 0.001). The mean survival time of entire group of patients was also well correlated with MIB-1 LI in astrocytic tumors(p = 0.015). Moreover, the mean survival time of the entire group of patients with Lis < 10 was $125.33{\pm}113.57weeks$, and the mean survival of those with $Lis{\geq}10$ was $60.71{\pm}62.58weeks$. This difference was also statistically significant(p = 0.004). Conclusion : The results of this study suggest that MIB-1 LI correlates with histological grades and might play a significant role in predicting the survival of patients with astrocytic tumors.

• Proceedings of the KSMRM Conference
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• 2003.10a
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• pp.21-21
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• 2003

목적： 악성뇌종양 주변부위의 역동자기공명영상에서의 시간신호강도곡선 양상으로 종양의 성장 양상이나 예후를 판단할 수 있는지를 알고자 한다. 대상 및 방법： Anaplastic oligodendroglioma 3예, Anaplastic astrocytoma 1예, Glioblastoma multiforme 1예, Malignant ependymoma 2예, Medulloblastorna 1예로서, 총 8예의 종양절제전, 혹은 후의 잔류 종양을 대상으로 하였다. Routine MRI에 추가하여 종양부위에서 Turbo spin echo T1 강조 역동자기공명영상을 하였으며, Gd-DTPA 0.1 mmol/kg를 급속 주사 한 후, TR/TE, 350/15, slice thickness 6 mm, slice number 3, NEX 2회, scan time은 15 초로 하여 5 분 동안 20회 영상을 얻었다. 가시적으로 조영증강이 없는 종양의 주변부위나 수술경계부위에 관심영역을 그려서 시간신호강도곡선을 얻었으며, 첫 회 조영제 통과시의 peak 이후에 신호가 감소하는 경우를 Normal pattern으로, peak 이후에 신호가 계속 유지되거나 증가하는 경우를 Tumor pattern으로 하였으며, Normal pattern과 Tumor pattern을 보인 예들을 구분하여 종양의 재성장 상태와 환자의 생존 기간을 비교 관찰하였다.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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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.

• Radiation Oncology Journal
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• v.14 no.2
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• pp.87-93
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• 1996

Purpose : To determine the incidence and prognostic effects of EGFR over-expression in the high-grade astrocytomas. Materials and Methods : With 23 paraffin blocks of the high-grade astrocytomas (7 anaplastic astrocytomas and 16 glioblastoma multiforme), expression of EGFR were evaluated by immunohistochemical staining employing polyclonal antibody raised to short cytoplasmic domain of the molecule. Result : Two out of 7 anaplastic astrocytomas and 9 out of 16 glioblastoma multiforme patients showed overexpression of EGFR(p=0.44). Three out of 11 patients of age below 55 and 8 out of 12 patients of age over 54 showed EGFR overexpression(p=0.141). Median survival of the EGFR negative anaplastic astrocytoma patient was 37 months. Median survival of the glioblastoma multiforme Patients were 11 months in EGFR negative group and 7 months in EGFR positive group. But survival difference was not significant (p=0.17). Conclusion There was a marked trend of increasing overexpression of EGFR in older patients. But survival of the glioblastoma multiforme decreased by the overexpression of the EGFR without significant.

• Journal of Korean Neurosurgical Society
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• v.49 no.6
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• pp.334-338
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• 2011

Objective : The incidence of leptomeningeal dissemination from malignant glioma is rare, so the clinical features of this are not well documented yet We attempted to determine the clinical features of leptomeningeal dissemination from malignant gliomas. Methods : We retrospectively analyzed 11 cases of leptomeningeal dissemination of malignant glioma, who were treated at our institution between 2006 and 2009. We investigated the clinical features of these patients by considering the following factors : tumor locations, the events of ventricular opening during surgery and the cerebrospinal fluid (CSF) profiles, including the cytology. Results : The group was composed of 9 males and 2 females. The histological diagnosis of their initial intracranial tumors were 4 primary glioblastoma, 3 anaplastic astrocytoma, 1 anaplastic oligoastrocytoma, 2 ganglioglioma and 1 pleomorphic xanthoastrocyotma with anaplastic features. The mean age of the patients at the time of the initial presentation was $42.8{\pm}10.3$ years. The mean time between surgery and the diagnosis of spinal dissemination was $12.3{\pm}7.9$ (3-28) months. The mean overall survival after dissemination was $2.7{\pm}1.3$ months. All our patients revealed a history of surgical opening of the ventricles. Elevated protein in the CSF was reported for eight patients who had their CSF profiles checked. Conclusion : We propose that in the malignant gliomas, the surgical opening of ventricles can cause the spinal leptomeningeal dissemination and the elevated protein content of CSF may be a candidate marker of leptomeningeal dissemination.

• Journal of Korean Neurosurgical Society
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• v.54 no.6
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• pp.489-495
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• 2013

Objective : To evaluate the efficacy of temozolomide (TMZ) chemotherapy for recurrent anaplastic oligodendroglioma (AO) and anaplastic oligoastrocytoma (AOA). Methods : A multi-center retrospective trial enrolled seventy-two patients with histologically proven AO/AOA who underwent TMZ chemotherapy for their recurrent tumors from 2006 to 2010. TMZ was administered orally (150 to 200 $mg/m^2/day$) for 5 days per 28 days until unacceptable toxicity occurred or tumor progression was observed. Results : TMZ chemotherapy cycles administered was median 5.3 (range, 1-41). The objective response rate was 24% including 8 cases (11%) of complete response and another 23 patients (32%) were remained as stable disease. Severe side effects (${\geq}$grade 3) occurred only in 9 patients (13%). Progression-free survival (PFS) of all patients was a median 8.0 months (95% confidence interval, 6.0-10.0). The time to recurrence of a year or after was a favorable prognostic factor for PFS (p<0.05). Overall survival (OS) was apparently differed by the patient's histology, as AOA patients survived a median OS of 18.0 months while AO patients did not reach median OS at median follow-up of 11.5 months (range 2.7-65 months). Good performance status of Eastern Cooperative Oncology Group 0 and 1 showed prolonged OS (p<0.01). Conclusion : For recurrent AO/AOA after surgery followed by radiation therapy, TMZ could be recommended as a salvage therapy at the estimated efficacy equal to procarbazine, lomustine, and vincristine (PCV) chemotherapy at first relapse. For patients previously treated with PCV, TMZ is a favorable therapeutic option as 2nd line salvage chemotherapy with an acceptable toxicity rate.

• Journal of Korean Neurosurgical Society
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• v.30 no.9
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• pp.1115-1119
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• 2001

Objective : Management strategies for pediatric chiasmatic-hypothalamic gliomas(CHG) include surgery, irradiation, chemotherapy and a combination of these modalities. This study was performed in order to compare the efficacy of various methods of treatment and to describe its optimal management. Material and Method : We have reviewed the results of management of 6 children with a diagnosis of CHG, who were observed closely during the last 8 years. The patients were aged 7 months to 15 years. Our patients presented with diencephalic syndrome, endocrine dysfunction, and progressive visual loss. None of these had evidence of neurofibromatosis-1. Treatment consisted of surgery alone(2), surgry and irradiation(2), surgery, irradiation and chemotherapy(1), and surgery and chemotherapy(1). Results : Four children had large exophytic suprasellar tumors and two showed diffuse midline lesions. Obstructive hydrocephalus was present in all patients. Pathologic examination revealed anaplastic astrocytoma in 1 and lowgrade astrocytoma in 5. Two patients, recently treated with radiation therapy following radical subtotal resection, showed significant tumor reductions and good clinical status. Four patients had partial tumor resection. Of these patients, two developed disease stabilization during follow-up period of 7 and 8 years, respectively. Life-threatening complications were noted in remaining two patients. Conclusion : CHG may follow an unpredicatable course and show a various reponse to each treatment modality. Further studies are indicated to define the optimal method of treatment of CHG in childhood.

• Journal of Korean Neurosurgical Society
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• v.30 no.6
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• pp.683-687
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• 2001

Objective : Angiogenesis, the proliferation of capillary endothelial cells, is a vital component in the development, progression, and metastasis of many human tumors. Vascular endothelial growth factor(VEGF) is an endothelial cell-specific mitogen and induces angiogenesis and vascular permeability. The features of glioblastoma, distinct from low grade astrocytomas, are the presence of necroses and vascular endothelial proliferation. In this study, we investigated VEGF expression in the different grades of astrocytomas and determined whether VEGF expression correlates with development of glioblastoma and progression of astrocytomas. Patients and Methods : Forty seven patients with astrocytic tumors(24 males and 23 females), aged 3 to 65 years, were evaluated. Immunohistochemical staining was carried out using labelled streptavidin biotin method and primary antibody was a antirabbit polyclonal Ab against N-terminus region of VEGF165(Oncogene research product, MA, USA). Immunoreactivity(IR) was classified into no IR(absent or a trace of stain), moderate IR and intense IR by level of staining amount and intensity. Results : Six pilocytic astrocytomas showed 3 no IR and 3 moderate IR, 10 astrocytomas showed 2 no IR, 6 moderate IR and 2 intense IR, 12 anaplastic astrocytomas showed I no IR, 7 moderate IR and 4 intense IR and 19 glioblastomas showed 1 no IR, 11 moderate IR and 7 intense IR. Immunoreactivity was significantly different between low and high grade of tumors but there was no significant difference between anaplastic astrocytomas and glioblastomas. Gemistocytic tumor cells represented the predominent VEGF-immunoreactive cell types, as compared with compactly-arranged small tumor cells. In glioblastomas VEGF IR was observed in both perinecrotic and vital tumor areas. Conclusion : VEGF seems to be a important angiogenic factor in anaplastic astrocytomas and glioblastomas and VEGF expression may contribute to neovascularization of human astrocytomas.

• Radiation Oncology Journal
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• v.16 no.4
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• pp.389-398
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• 1998

Purpose : To evaluate the role of conventional postoperative adjuvant radiotherapy in the management of supratentorial malignant glioma and to determine favorable prognostic factors affecting survival. Materials and Methods : From Sep. 1985 to Mar. 1997, the number of eligible patients who received postoperative radiotherapy completely was 69. They ranged in age from 7 to 66 years (median, 47). Forty-two (61$\%$) patients were glioblastoma multiforme and the other 27 (39$\%$) were anaplastic astrocytoma. Twenty patients (29$\%$) had Karnofsky score equal or more than 80 preoperatively. Forty-three patients (62$\%$) had symptom duration equal or less than 3 months. Twenty-four patients (35$\%$) had gross total resection and forty patients(58$\%$) had partial resection, the remaining five patients (7$\%$) had biopsy only. Radiotherapy dose ranged from 50.4 Gy to 61.2 Gy (median, 55.8; mode, 59.4) with fraction size of 1 8 Gy-2.0 Gy for 33-83 days(median, 48) except three patients delivered 33, 36, 39 Gr, respectively with fraction size of 3.0 Gy due to poor postoperative performance status. Follow-up rate was 93$\%$ and median follow-up period was 14 months. Results : Overall survival rate at 2 and 3 years and median survival were 38$\%$, 20$\%$, and 16 months for entire patients; 67$\%$, 44$\%$, and 34 months for anaplastic astrocytoma; 18$\%$, 4$\%$, and 14 months for glioblastoma multiforme, respectively (p=0.0001). According to the extent of surgery, 3-year overall survival for gross total resection, partial resection, and biopsy only was 38$\%$, 11$\%$, and 0$\%$, respectively (p=0.02) The 3-year overall survival rates for patients age 40>, 40-59, and 60< were 52$\%$, 8$\%$, and 0$\%$, respectively (p=0.0007). For the variate of performance score 80< vs 80>, the 3-year survival rates were 53$\%$ and 9$\%$, respectively (p=0.008). On multivariate analysis including covariates of three surgical and age subgroups as above, pathology, extent of surgery and age were significant prognostic factors affecting overall survival. On another multivariate analysis with covariates of two surgical (total resection vs others) and two a9e (50> vs 50<) subgroups, then, pathology, extent of surgery and performance status were significant factors instead of age and 3-year cumulative survival rate for the five patients with these three favorable factors was 100$\%$ without serious sequela. Conclusion : We confirmed the role of postoperative conventional radiotherapy in the management of supratentorial malignant glioma by improving survival as compared with historical data of surgery only. Patients with anaplastic astrocytoma, good performance score, gross total resection and/or young age survived longest. Maximum surgical resection with acceptable preservation of neurologic function should be attempted in glioblastoma patients, especially in younger patients. But the survival of most globlastoma patients without favorable factors is still poor, so other active adjuvant treatment modalities should be tried or added rather than conventional radiation treatment alone in this subgroup.