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Objective: To analyze the prognosis factors of cerebrospinal fluid (CSF) spread after surgery in glioblastoma (GBM) patients when tumors progressed and the effect factors on prognosis. Methods: A retrospective study was conducted on 124 patients who were pathologically diagnosed as glioblastoma after surgery, and found tumor progressed during regularly follow-up at Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University between January 2009 and August 2017.There were 82 males and 42 females, aged 47.9 years(range: 19 to 75 years) .Patients were divided into local recurrence group(96 cases) and CSF spread group (28 cases) .Clinical data were recorded in detail and compared by independent sample t test or χ(2) test.Kaplan-Meier survival curves was used to demonstrated the distribution of progression free survival (PFS) overall survival (OS) and post progression survival (PPS), and differences between local recurrence and CSF spread groups were assessed by Log-rank test.Cox proportion hazard regression analysis was used to identify independent prognostic factors. Results: Logistics regression analysis showed ventricle entry was the only prognosis factor of CSF spread ( OR= 2.667, 95 % CI : 1.128 to 6.304, P= 0.025).No significant distinction was observed in PFS between CSF spread group and local recurrence group(7.0 months vs .9.3 months, P= 0.066).However, OS and PPS were substantially shortened in CSF spread group (13.0 months vs .23.0 months, P= 0.011; 6.0 months vs .11.0 months, P= 0.022, respectively).Mutations of isocitrate dehydrogenase gene, distant spread, gross-total resection, Ki-67 index>30% were independent prognostic factors of GBM patients. Conclusions: Ventricle entry is a prognosis factor for CSF spread, after which the median OS and PPS are markedly diminished.However, ventricle entry is not independent prognosis factor shortening survival.

Glioblastoma (GBM) is the most common primary intracranial malignancy. The comprehensive treatment mode based on surgical resection has become the key to improve the prognosis of GBM and the quality of life of patients. This article reviews the progress of GBM in the fields of surgery, radiotherapy, chemotherapy, targeted therapy and immunotherapy during the past twenty years, mainly explores the similarities and differences between the treatment strategies of newly diagnosed and recurrent GBM and analyzes the difficulties in the current clinical practice of GBM.

Objective: To analyze the treatment effect of patients with glioblastoma (GBM) and explore prognostic factors. Methods: The clinical data of 635 patients diagnosed as GBM at Neurosurgical Oncology Department Ⅳ of Beijing Tiantan Hospital, Capital Medical University from January 2007 to March 2018 were retrospectively reviewed. There were 386 males and 249 females with an age of (48.7±11.8) years (range: 18-75 years). Patients were divided into three groups according to the time of admission: 2007-2010 group( n= 174), 2011-2014 group ( n= 237) and 2015-2018 group ( n= 224). Kaplan-Meier plot was used to analyze the effects of different treatment periods, treatment schemes and clinical factors on the survival of patients with GBM. Cox proportion hazard regression analysis was used to identify independent prognostic factors. Results: The median progression-free survival (PFS) and overall survival (OS) of patients in 2007-2010 group, 2011-2014 group, 2015-2018 group was 9.0 months (95% CI : 7.5-10.5), 10.0 months (95% CI : 8.8-11.2), 12.0 months (95% CI : 10.7-13.3) and 17.0 months (95% CI : 13.2-20.8), 20.0 months (95% CI : 16.9-23.1), 23.0 months(95% CI : 17.5-28.5), respectively. The PFS and OS of patients improved significantly over the years (χ(2)=9.693, P= 0.008 and χ(2)=8.616, P= 0.013). Multivariate survival analysis showed that age, extent of resection, radiotherapy and tumor distant dissemination were independent prognostic factors (all P< 0.05). Conclusions: With the continuous development of clinical treatment regimen, the therapeutic effect of Chinese GBM patients has improved remarkably. Age, extent of resection, radiotherapy and tumor distant dissemination are independent prognostic factors associated with survival time.

Objective: To investigate the clinic effect of the sodium fluorescein-guided microsurgical resection of glioblastoma. Methods: In a retrospective clinical study, 82 patients with glioblastoma confirmed by post-operative pathologic inspection in the Department of Neurosurgery of Tianjin Huanhu Hospital from January 2016 to June 2017 were randomly divided into sodium fluorescein (FL) group (42 cases) and traditional microsurgical (TM) group (40 cases). The tumors were removed by the sodium fluorescein-guided surgical procedure in the FL group. The tissues which displayed different intensity of fluorescent staining were taken for the pathologic inspection. The resection of tumors were completed under common microscope in the TM group. The two groups of patients underwent MRI enhanced scan at 48 hours after operation to determine the degree of tumor resection. The rate of gross total resection, postoperative complication, recurrent rate of two groups were compared by χ(2) test or Fisher exact test. Results: Totally 135 fluorescent staining samples were obtained in the FL group. Forty-two samples were showed strong fluorescent staining, and all samples were proved to be tumor tissue by pathologic inspection, the sensitivity of FL was 100%. Thirty-seven gliomas were detected from 45 samples of faintly fluorescent staining, sensitivity of FL was 82.3%. Eight gliomas were found from 48 samples of non-fluorescent staining, the specificity of FL was 83.3%. The total resection rate of sodium fluorescein group was 85.7% (36/42), higher than that of traditional microsurgical group (62.5% (25/40)) (χ(2)=5.795, P =0.016). Two groups of patients were followed up to 6 months after the operation, and 6 cases (14.3%, 6/42) were recurred in the FL group. Among them, 1 case died and the average Karnofsky performance score was 82.2±15.2. There were 12 recurrent cases (33.3%, 12/36) in the TM group, of which 2 cases were died and the average Karnofsky performance score was 76.9±20.3. There was significantly statistical difference in recurrent rate (χ(2)=3.962, P =0.047). Conclusions: The sensitivity and specificity of fluorescein staining in glioblastoma tissue are high. And the application of sodium fluorescein-guided microsurgical resection of glioblastoma is safe and simple. Therefore, it is helpful to improve the total resection rate of glioblastoma patients and reduce the recurrence rate.

Objective: To evaluate the efficacy of intraoperative magnetic resonance imaging (iMRI) and multimodal navigation in surgical resection of glioblastoma., Methods: Between February 2009 and July 2010, 76 glioblastoma patients underwent surgical resection guided by iMRI and multimodal navigation. The cohort consisted of 43 male and 33 female patients, with a mean age of 49 years (range: 14-79 years). Rates of gross total resection (GTR) and extent of resection (EoR) were calculated at first and final iMRI scans.Pearson χ(2) test was used to compare the rates of GTR., Results: iMRI and multimodal navigation were successfully implemented in all cases. Rates of GTR were misestimated by neurosurgeons in 24 cases (31.6%), which were confirmed by first iMRI. Total tumor resection were achieved in 20 cases (26.3%) as a result of iMRI scan, increasing the rates of gross total resection from 52.6% to 78.9% (χ(2) = 11.692, P = 0.001). Extent of resection in 28 patients who underwent further tumor resection were increased from 81.5% to 98.1%, leading to the overall extent of resection improved from 92.3% to 98.4%. At 3-month follow-up, 3 cases (3.9%) developed permanent neurologic deficits. The mean clinical follow-up was 15.6 months (range 3.0-45.0 months). The 2-year overall survival rate was 19.7%. The median progression-free survival of gross total resection group was 12 months (95% CI: 10.1-13.9 months), compared with 9 months (95%CI: 7.9-10.1 months) of the subtotal resection group (χ(2) = 4.756, P = 0.029). The overall survival of gross total resection group was 16 months (95% CI: 13.7-18.3 months), compared with 12 months (95% CI: 9.7-14.3 months) of the subtotal resection group (χ(2) = 7.885, P = 0.005)., Conclusion: Combined with multimodal navigation, iMRI helps maximize surgical resection of glioblastoma, preserving neurological function while increasing progression-free survival and overall survival.

Objective: To study the correlation between loss of heterozygosity (LOH) on chromosome 10q and pathologic features, pathogenesis, prognosis of astrocytic tumors., Methods: LOH on 10q was studied by interphase fluorescence in-situ hybridization (FISH) in 85 cases of astrocytic tumor, including 35 cases of WHO grade II tumors and 50 cases of WHO grade IV tumors., Results: LOH on 10q was detected in 6 cases (17.1%) of diffuse astrocytoma (WHO grade II) and 34 cases (68.0%) of glioblastoma (WHO grade IV). 10q polysomy was detected in 7 cases (20.0%) of diffuse astrocytoma and 11 cases (22.0%) of glioblastoma. The rates of LOH on 10q in young age group and elderly group were 36.4% (12/33) and 82.4% (28/34), respectively. The difference was of statistical significance (P < 0.05). The rates of LOH on 10q in the diffuse astrocytoma and glioblastoma were 21.4% (6/28) and 87.2% (34/39), respectively. The difference was also statistically significant (P < 0.05). Univariate survival analysis showed that patient age, pathologic grade and 10q on LOH correlated with duration of survival (P < 0.05)., Conclusions: There are correlation between 10q LOH, patient age and pathologic grade of astrocytic tumors. LOH on 10q is also related to the pathogenesis of astrocytic tumors and is helpful in predicting prognosis.

Background & Objective: Malignant glioma cells are resistant to most chemotherapeutic agents. Nitrosourea and temozolomide (TMZ) are main agents for treating malignant glioma. Resistance of malignant glioma to these agents is frequently associated with high levels of DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT). This study was to evaluate the efficacy of individualized chemotherapy, according to chemotherapy sensitivity and resistance assays (CSRAs) and MGMT expression pattern, on malignant glioma, and observe the adverse events., Methods: The pathologically confirmed malignant glioma patients, treated by operation at Cancer Center of Sun Yat-sen University from Dec. 2001 to Feb. 2006, were enrolled. The fresh tumor tissues obtained during operation were immediately sent for CSRAs using MTT assay. The expression of MGMT protein was detected by immunohistochemistry. After radiotherapy,the patients received chemotherapy according to the results of CSRAs and MGMT expression. The patients were evaluated for response to chemotherapy according to WHO criteria, and for toxicity according to National Cancer Institute (NCI) criteria., Results: Forty-two patients were evaluated for response to chemotherapy. Seven patients received 2 chemotherapy regimens consecutively, therefore, overall 49 cases were evaluable. Of the 49 cases, 6 (12%) achieved complete remission (CR), 10 (20%) achieved partial remission (PR), 20 (41%) had stable disease (SD), and 13 (27%) had progressive disease (PD). The objective response rate (CR and PR) was 33%, and the disease control rate (CR, PR, and SD) was 73%. Hematologic toxicities were the main adverse events observed in this study, included grade IV anemia (1%), grade III-IV leukopenia (28%), and grade III-IV thrombocytopenia (8%). Non-hematologic toxicities mainly included nausea/vomit, fatigue, and alopecia., Conclusion: Individualized chemotherapy based on in vitro CSRAs and MGMT expression for patients with malignant glioma could improve overall response rate.

Objective: To further study the clinical features, diagnosis, and surgery outcome of brain-stem gliomas., Methods: Totally 311 patients with brain-stem gliomas received surgery operations in our hospital from 1980 to the end of 2001. The clinical data, neuroimages, growth patterns, and operative feasibility were analyzed., Results: Different brain-stem gliomas showed different growth patterns. In this series, total excision rate of the tumor was 40.5%, subtotal 29.9%, partial 29.6%, and operative mortality 1.3%. Among 311 patients, 72.4% patients had been improved and stable in their symptoms after operation, and 27.6% deteriorated or having transitory new signs. Five years survival rate is 67% in ependymoma patients, 42% in astrocytoma patients. None of brain-stem glioblastoma patients survived up to 5 years., Conclusions: The histology and growth pattern of brainstem gliomas varies. The patients with well-differentiated gliomas of brain-stem may be cured by microsurgical removal. For malignant ones, partial removal may prolong survival and facilitate the following combined therapy.

Background & Objective: Surgery is the major treatment for glioma, and radiotherapy is often needed after operation. This study was to evaluate prognostic factors of patients with cerebral glioma treated with radiotherapy., Methods: Records of 158 patients with cerebral glioma, including 123 patients with astrocytoma (AC), 12 patients with oligodendroglioma (OD) or mixed oligoastrocytoma (OA), and 23 patients with glioblastoma multiforme (GBM), received radiotherapy in our center were analyzed. Eighty patients received total resection, 77 received subtotal resection, and 1 received biopsy before radiotherapy. Median radiation dose was 58 Gy (36-75 Gy). Median waiting time from operation to radiotherapy was 29 days (12-261 days). Sixty-eight patients received chemotherapy before or after radiotherapy. Cox model was used for univariate and multivariate analysis., Results: Median follow-up was 23 months (2-62 months), 27 patients relapsed, and 57 patients died. The 2- and 4-year overall survival rate were 66.5% and 45.7%. Univariate analysis showed that histologic grade (I/II vs. II/IV), histologic type (AC/OD vs. GBM), Karnofsky performance state (KPS) before radiotherapy (>/=80 vs.< 80), extent of resection (total vs non-total), and age(40 years) were significant predictors in association with overall survival rate of patients with glioma. Multivariate analysis showed that histologic grade (P=0.001), age (P=0.006), KPS before radiotherapy (P=0.009), and extent of resection (P=0.037) were independent prognostic factors of glioma., Conclusion: Low grade (I/II), age /=80 before radiotherapy, and total resection are independent factors for predicting better survival of glioma patients.

Background & Objective: Astrocytomas, constitute about 75% of neuroepithelial tumors, is one of the most common primary tumors in central nervous system with fairly high incidence and poor prognosis. Individualized multimodality is the hope for improving prognosis of patients with astrocytoma. This study was designed to investigate the efficiency of individualized treatment of microsurgery, radiotherapy, and chemotherapy for 62 patients with astrocytoma., Methods: Sixty-two patients with astrocytoma in study group were treated with individualized multimodality of microsurgery, postoperative radiotherapy, and/or postoperative chemotherapy according to in vitro sensitivity assay. After microsurgery, 59 patients accepted radiotherapy, 46 patients received chemotherapy. Fifty patients with astrocytoma in control group were treated with conventional treatment of surgery, chemotherapy, and radiotherapy. After surgery, 31 patients received radiotherapy following by BCNU chemotherapy, while 19 patients accepted BCNU chemotherapy following radiotherapy. Pathologic diagnosis of patients in study group were 19 cases of grade, 32 cases of grade III, and 11 cases of grade IV; in control group were 13 cases of grade II, 28 cases of grade III, and 9 cases of grade IV. Mean follow-up time were 25.8 months, and the outcome was evaluated by MRI, KPS, and survival rate., Results: Tumor total resection rate in study group was 67.7%, while that in control group was 58.0%. There was no significant difference of KPS and survival rate in patients with low-grade astrocytoma between 2 groups, while the outcome of patients with malignant astrocytoma was significantly improved by individualized treatment. In study group, 2-year expectant survival rate of patients with astrocytoma of grade III, and grade IV were 93.7%, and 36.3%, while in control group were 67.5%, and 22.2% (P< 0.05). In glioblastoma patients, median survival time of study group was 18.68 months, while that of control group was 12.83 months (P< 0.01)., Conclusion: Individualized microsurgery may improve the total resection of astrocytoma, and benefit to postoperative treatment.Individualized radiotherapy/chemotherapy may prevent patients from some complications. Individualized management may improve prognosis of patients with astrocytoma, particularly malignant astrocytoma.

Background & Objective: Prognosis of glioma is still poor, its main treatment is surgery. The extent of tumor resection relates with prognosis. This study was to evaluate the extent of resection, post-operative Karnofsky performance scale (KPS), and survival rate of the glioma patients received microsurgery., Methods: Records of 183 glioma patients received microneurosurgery were retrospectively analyzed, the extent of resection, post-operative KPS, and survival rate of patients were evaluated. Different microsurgical techniques were applied according to the location of gliomas. En bloc resection was performed for gliomas in non-functional areas by dissecting the tumors along edema area with high-power bipolar electrocoagulation. The tumors in functional areas were separated along cortex sulcus, the central part of tumor was removed firstly, and residual part was resected with low-power electrocoagulation. Gliomas close to important vessels were sucked, and electrocoagulation seldom performed., Results: Among 183 cases of glioma, 85 in non-functional area, 47 in functional area, and 51 close to important vessels. Total and sub-total resection was performed in 163 patients (89.1%). The average post-operative KPS was 74. The KPS was decreased in 23 patients, increased in 44 patients, and stable in 116 patients. Patients were followed up for 12-216 months with an average of 47.8 months. The follow-up rate was 100%. Among 113 patients with long-term follow-up (>/=5 years), 5-year survival rates of low-grade, and high-grade astrocytoma patients were 75.4% (52/69), and 18.2% (8/44)., Conclusion: Using different microsurgical patterns according to location of glioma, maximal resection of tumor may achieve with protection of neurological function.

Objective: To investigate molecular genetic alterations associated with primary and corresponding recurrent glioblastoma multiforme(GBM) and to identify which chromosomal regions of the whole genome may be involved in the recurrence of primary GBM., Methods: A high-resolution allelotyping study of one patient's primary GBM and corresponding recurrent GBM was performed by PCR-based loss of heterozygosity(LOH) analysis with the use of 382 fluorescent dye-labeled polymorphic microsatellite markers covering all 22 autosomes. The mean genetic distance between two flanking markers is 10 cM., Results: LOH at locus D9S157 on 9p21 and at loci D10S537, D10S185, D10S192, D10S597, D10S587, D10S217 on 10q21.3-26.3 was observed in the primary GBM. As for corresponding recurrent tumor, LOH was observed not only in expanded regions on 9p21 and 10q21.3-26.3 but also on multiple other chromosomal arms, including 1q, 7p,7q, 21q, 20p, 20q, 10p, 19p, 19q., Conclusion: Chromosome 9p and 10q may be involved in the development of this GBM. Although histopathological diagnoses of the primary and corresponding recurrent tumor are identical, the recurrence of GBM is characterized by an increased involvement of molecular genetic abnormalities and may be accompanied by inactivation of more tumor suppressor genes.

Background & Objective: Though radiosurgery has been used for more than 10 years, the value of radiosurgery for malignant glioma has not been clarified. This paper was designed to investigate efficacy of radiosurgery to malignant glioma by analyzing the prognostic factors affecting prognosis of malignant gliomas treated with linac radiosurgery., Methods: Fifty-eight patients with deep situated malignant gliomas, 28 anaplastic astrocytomas(AA) and 30 glioblastomas (GBM), aged from 7 to 70 years, were analyzed. The mean volume of tumor was 12.08 cm3, and mean prescription dose for linac radiosurgery was 19.42 Gy. The results were analyzed with Kaplan-Meier curve and Cox regression., Results: There were 44.8% of the tumors shrank. Median tumor local control interval was 10 months(15 months for AA and 9 months for GBM). Tumor local control probability was 37.9% for 1 year and 10.3% for 2 years. Median survival was 22.5 months for AA and 13 months for GBM and 15 months for all patients. The survival probability was 79.3% at 1 year and 20.6% at 2 years. Isocenter numbers and tumor volume were the prognostic factors for tumor control, but conformity index was prognostic factor for survival as determined by Cox regression analysis. Considered of pathology, only isocenter number and target volume significantly affected the tumor control interval. Complication appeared in 44.8% of the patients and the median interval of complication onset was 8 months. Symptomatic cerebral edema was observed in 31.0% of the patients., Conclusion: Linac radiosurgery can effectively improve tumor local control and elongate survival for the patients with deep situated malignant gliomas. Tumor volume is the prognostic factor for tumor control, while conformity index is prognostic factor for survival.

Objective: To find the superlative way of surgical removal of glioblastoma multiform under functional cortex by comparative study of 123 patients., Method: Surgical approaches include direct and total resection of tumors, trans-functional cortex or adjacent area beyond functional cortex. They were compared with partial tumor resection plus external/internal decompressive procedure, total removal of tumor plus functional cortex resection. Comprehensive analysis was made., Result: Total removal of tumors both trans-functional or adjacent cortex prolonged the survival time of patients. As a result, minimal damage was observed in patients with both approaches, which are helpful for recovery of impaired cerebral function. On the other hand, partial resection of tumors in spite of combining with decompressive procedure or functional cortex resection did not show the same benefit., Conclusion: Surgical resection of glioblastoma multiform through trans-functional cortex or adjacent cortex beyond functional area is superior to other approaches both in dealing with total tumors removal and cerebral function recovery. But the resection through adjacent cortex beyond functional area in recovery of impaired cerebral function is more effective.

A retrospective analysis of 73 patients with glioblastoma multiforme treated with surgery plus radiotherapy (63 cases) or surgery alone (10 cases) showed that the 5-year survival was 16% versus 0% and the median survival time was 14 versus 5 months. The median survival time in patients receiving postoperative radiotherapy was almost 3 times as long as that in patients treated with surgery alone. The difference in survival was insignificant between patients treated with a local extended field and those with whole brain plus local irradiation. The age, sex, course of disease, extent of operation and dose of irradiation are the factors influencing prognosis.