低级别胶质瘤的治疗

低级别胶质瘤占胶质瘤的15%～25%,生物学特性及临床预后相差较大。如何治疗低级别胶质瘤仍存在较大争议。根据大宗的文献资料,从循证医学的角度考虑,目前多数认为,手术切除肿瘤能够明确病理、缓解肿瘤的占位症状和延缓病情的进展,除症状不明显、全身情况差或肿瘤位于脑干等深部重要功能区的患者外,多宜行手术。手术应在最大限度保全神经功能的前提下尽可能彻底切除肿瘤,对切除肿瘤确有困难的也应尽可能做活检(包括立体定向活检)。术后应在72小时内复查MRI,明确肿瘤切除程度。放疗在低级别胶质瘤治疗中的作用逐渐被肯定。除年龄小于40岁,以癫痫为主要临床表现,且手术后影像学证明肿瘤切除彻底的患者外,其他低级别胶质瘤患者建议行术后放射治疗。在化疗方面,传统的PCV方案及不良反应较小的口服化疗药替莫唑胺,对低级别胶质瘤显示出一定的疗效,但仍需进行深入的研究。此外,分子靶向治疗及生物治疗等手段也被考虑应用于低级别胶质瘤的治疗,但还有待前瞻性的临床研究。     

脑胶质瘤146例手术效果及预后因素分析

背景与目的:脑胶质瘤占所有颅内肿瘤的一半左右,且好发于中青年人,对家庭和社会影响较大。本文总结脑胶质瘤手术治疗效果并探讨影响预后的因素。方法:回顾性分析我院近5年来手术治疗的脑胶质瘤患者病例资料并随访,对手术效果及预后行单、多因素综合分析。结果:显微手术治疗146例患者,男性77例,女性69例;年龄7～80岁,平均38.6岁;低级别胶质瘤(LGG)74例,高级别胶质瘤(HGG)72例,全切和大部切除117例,部分切除和活检29例,无手术死亡。术前、术后平均KPS为63.1、81.5分,术后平均升高18.4分,术后复发51例;获得完整随访资料71例,男性42例,女性29例;全切、次全切、部分切除加活检例数分别为21、35、15,共死亡29例,死亡比例40岁以下9/38,40岁及以上20/33;LGG8/36,HGG21/35。结论:年龄、肿瘤级别、肿瘤切除程度、术前术后KPS及放化疗与胶质瘤患者预后密切相关;年龄、肿瘤级别是预后的最危险因素,术后KPS及肿瘤切除程度与患者预后正相关。     

高分级脑胶质瘤术后精确放疗患者的预后影响因素

目的:分析高分级脑胶质瘤术后精确放疗患者预后的危险因素及干预对策。方法:回顾自2009年6月至2013年6月入我院的病理诊断为高分级脑胶质瘤术后精确放疗的患者资料。对患者的一般情况如性别、年龄、手术切除程度、病理分级、化疗、放疗量、KPS评分、术前癫痫发作、总生存期（随访2年）等数据进行分析,评价高分级脑胶质瘤术后精确放疗患者预后的危险因素。结果:在123例患者中,年龄16~86岁,平均发病年龄46.9岁,男性平均发病年龄42.0岁,女性平均发病年龄49.5岁。小于40岁患者68例,大于等于40岁患者55例。从发病到明确诊断平均时间9.8月,中位生存时间19个月,1年生存率69%,2年生存率37.4%。单因素分析显示,年龄、手术切除程度、病理分级、化疗与高分级脑胶质瘤术后精确放疗患者预后显著相关（P＜0.05）,性别、放疗、术前癫痫发作、KPS评分与高分级脑胶质瘤术后精确放疗患者预后无明显相关（P>0.05）。多因素COX回归分析显示,年龄<40岁（RR=1.844,95%CI:1.047~3.249）、肿瘤全切（RR=2.348,95%CI:1.389~3.968）、病理分级3级（RR=2.632,95%CI:1.479~4.684）、同步替莫唑胺化疗（RR=0.557,95%CI:0.329~0.944）能够显著延长患者的总生存时间。结论:年龄、手术切除程度、病理分级、化疗等是高分级脑胶质瘤术后精确放疗患者生存预后的危险因素。年龄<40岁、肿瘤全切、病理分级低、同步化疗患者生存预后较好。     

胶质瘤68例放射治疗疗效及预后因素

目的 回顾分析胶质瘤术后患者放射治疗的疗效，探讨影响放射治疗胶质瘤的顸后因素。方法 资料完整的胶质瘤患者67例，其中低分级39例，高分级24例，室管膜瘤4例。所有患者均进行了手术切除（其中全切术31例，次全切除术36例），手术后一月内接受^60Coγ，射线放射治疗。Kaplan—Meier法计算生存率，Cox比例风险模型进行预后的多因素分析。结果单因素分析显示，患者年龄〈45岁、低分级胶质瘤、手术全切肿瘤者的1年，3年，5年生存率较高。多因素分析显示，年龄、病理分级、手术切除程度是独立预后因素。结论年龄、病理分级、手术切除程度是影响放射治疗胶质瘤的重要预后因素。     

脑胶质瘤术后放射治疗疗效及预后75例分析

背景与目的:手术难以真正彻底切除脑胶质瘤,术后放射治疗已成为常规。本文回顾性分析胶质瘤患者术后放射治疗的疗效,探讨影响放射治疗胶质瘤预后的因素。方法:对资料完整的75例胶质瘤患者进行回顾性分析。其中低分级胶质瘤28例,高分级胶质瘤40例,未明确分级的7例。手术全切65例,次全切5例,单纯活检5例。术后接受放射治疗的中位时间为35天,其中16例采用60Coγ射线,59例采用直线加速器光子线和电子线混合线束。Kaplan-Meier法计算生存率,Cox比例风险模型进行预后的多因素分析。结果:低分级胶质瘤的1、3、5年生存率分别为92.0%、66.9%、61.7%;高分级胶质瘤的1、3、5年生存率分别为76.9%、38.0%、22.4%。年龄<40岁、低分级胶质瘤、手术全切肿瘤、放疗剂量≥60Gy的患者预后较好。结论:年龄、病理分级、手术切除程度、放疗剂量是影响放射治疗胶质瘤预后的重要因素。     

112例脑胶质瘤术后放射治疗的临床预后分析

目的回顾性分析脑胶质瘤患者术后放射治疗的疗效,探讨评价影响放射治疗胶质瘤预后的因素。方法对临床资料完整的112例脑胶质瘤患者进行回顾性分析,其中Ⅰ～Ⅱ级胶质瘤54例,Ⅲ～Ⅳ级58例。手术全切61例,次全切43例,单纯活检8例。术后等待放射治疗的中位时间为27.5 d,放射治疗的中位剂量为56 Gy。采用Cox比例风险模型进行预后的单因素和多因素分析。结果低分级胶质瘤的1,3年生存率分别为88.9%和53.0%;高分级胶质瘤的1,3年生存率分别为68.9%和17.2%。年龄≤40岁、低分级胶质瘤、手术全切肿瘤、放疗前Karnofsky评分≥80分的患者预后较好。结论年龄、病理分级、手术切除程度以及放疗前的功能状况是影响胶质瘤放射治疗预后的独立因素。     

164例胶质瘤术后放射治疗疗效及预后

目的：回顾性分析胶质瘤患者术后放射治疗的疗效。探讨影响放射治疗胶瘤预后的因素。方法：对资料完整的164例胶质瘤患者进行回顾性研究,其中低分级胶质瘤79例,高分级胶质瘤47例,室管膜细胞瘤24例,少突胶质细胞瘤14例。手术全切71例,次全切86例,单纯活检7例,术后2周至1个月内接受放射治疗,其中135例采用^60Coγ射线,29例采用加速器光子线和电子线混合线束,寿命表法计算生存率,Cox比例风险模型进行预后的多因素分析。结果：低分级胶质瘤的1、3、5年生存率分别为91％、89％、82％;高分级胶质瘤的1、3、5年生存率分别为53％、40％、365。年龄＜40岁、低分级胶质瘤、手术全切肿瘤的患者预后较好。结论：年龄、病理分级、手术切除程度是影响放射治疗胶质瘤预后的重要因素。     

脑胶质瘤放射治疗的预后因素分析

目的评价和分析脑胶质瘤患者放射治疗的预后因素。方法选择接受放射治疗的脑胶质瘤术后患者162例,采用COX模型对预后因素进行单因素和多因素分析。结果平均随访时间30个月,复发14例,死亡45例。单因素分析结果显示,病理分级、病理类型、放疗前功能状态、手术切除范围和年龄是影响胶质瘤患者总生存率的因素。多因素分析结果显示病理分级、病理类型、年龄、放疗前功能状态、手术切除范围和放疗技术是影响总生存率的独立预后因素。结论低分级胶质瘤、星形细胞瘤和少突胶质瘤、年龄≤40岁、放疗前Kamofsky评分≥80分和肿瘤全切是预后较好的独立因素。     

脑胶质瘤患者预后影响因素分析

[目的]探讨脑胶质瘤患者预后影响因素,以提高胶质瘤患者术后生存率。[方法]外科手术后经病理确诊为脑胶质瘤的患者158例,查找病历和电话随访收集其资料,生存分析单因素分析使用Kaplan-Meier法计算生存率,并采用Log-rank检验;多因素分析采用Cox分析。[结果]单因素分析表明影响预后的因素有：年龄、肿瘤级别、KPS评分、术后放疗和化疗。多因素分析显示年龄、肿瘤级别、KPS评分、术后放疗和化疗是影响预后的独立因素。[结论]年龄小、级别低、KPS评分高的患者术后预后较好,术后辅助放疗或者化疗有助于改善预后。     

外科治疗食管、贲门癌预后与年龄的关系

目的　回顾性研究了手术切除食管癌和贲门癌的病人 ,评价了手术时的年龄与预后的关系。方法　从 1983年到 1995年 ,我科共手术切除食管癌和贲门癌 14 49例 ,将病人按手术时的年龄分成 7个组 ,然后根据病人的性别 ,年龄分别计算其生存率 ,使用图表法进行对比。结果　通过比较我们发现年龄小于 40岁和大于 70岁的病人其总的预后是差的 ,而 40～ 70岁之间的病人 ,其五年生存率差别不大。 <3 0岁 ,3 0～ 3 9岁 ,40～ 49岁 ,5 0～ 5 9岁 ,60～ 69岁 ,70～ 79岁和 >80岁的病人 ,五年生存率分别是 7 5 % ,10 3 % ,3 0 6% ,3 7 1% ,3 4 2 % ,13 4%和 0 0 %。结论　年轻病人预后差的原因可能是肿瘤的分化差 ,转移发生较快 ,姑息性手术比率较高有一定的关系 ,而高龄病人长期生存率低可能与其它疾病导致死亡率增高有关。因此 ,我们认为对食管癌和贲门癌病人行手术治疗时 ,特别对于年轻或高龄病人 ,年龄是一个预后因素。     

胶质瘤中端粒酶逆转录酶启动子区突变分析及其预后意义

目的:探讨端粒酶逆转录酶(TERT)启动子区突变与胶质瘤患者临床病理指标的关系及其对预后的影响。方法:应用Sanger测序技术检测78例脑胶质瘤组织中TERT启动子区C228T和C250T位点的突变情况,分析TERT启动子区突变与临床病理指标的关系及其对预后的影响。结果:TERT启动子区突变在脑胶质瘤中的发生率为32.1%,在低级别(Ⅰ~Ⅱ)和高级别(Ⅲ~Ⅳ)胶质瘤中突变分别占28.0%和34.0%。其中少突星形细胞瘤中突变占57.1%,胶质母细胞瘤中突变占44.4%,低级别星形细胞瘤和少突胶质细胞瘤中突变分别占28.6%和23.1%。TERT启动子区突变与胶质瘤患者术后生存时间显著相关,突变型术后生存时间显著短于野生型(P=0.001)。按低级别和高级别分组独立分析后发现,TERT启动子区突变在低级别组和高级别组中均与不良预后相关(P值分别为0.019和0.018)。Cox回归分析表明,TERT启动子区突变和术后放化疗是独立的预后影响因素(P=0.002,HR=3.486,95%CI: 1.591 ~7.637;P=0.004,HR=0.331,95%CI:0.156～0.699)。结论:TERT启动子区突变频繁发生于脑胶质瘤中,突变型胶质瘤患者预后不良。     

Vascular Endothelial Growth Factor (VEGF) in Astrocytic Gliomas – A Prognostic Factor?

Survival in astrocytic gliomas is closely related to WHO tumor grade. Within one tumor grade, especially in grade II and III tumors, the clinical course is variable and can hardly be predicted by histological criteria. Neovascularization is a neuropathological hallmark in high grade gliomas and angiogenic factors may play an important role in malignant tumor progression. Therefore, 162 primary astrocytic gliomas (57 astrocytomas WHO grade II, 27 astrocytomas WHO grade III and 78 glioblastomas WHO grade IV) were investigated immunohistochemically for expression of vascular endothelial growth factor (VEGF), which is considered to represent the main angiogenic factor in astrocytic gliomas. Clinical data known to influence prognosis were documented. VEGF expression was found in 21 of 57 astrocytomas WHO grade II (36.8%), in 18 of 27 astrocytomas WHO grade III (66.7%) and in 50 of 78 glioblastomas (64.1%). A strong correlation between VEGF expression and survival was found within the whole study group, however, within one tumor grade no such correlation was obvious. In a multifactorial analysis VEGF expression was not found to be an independent prognostic factor in astrocytic gliomas.     

Identification of high risk anaplastic gliomas by a diagnostic and prognostic signature derived from mRNA expression profiling

Anaplastic gliomas are characterized by variable clinical and genetic features, but there are few studies focusing on the substratification of anaplastic gliomas. To identify a more objective and applicable classification of anaplastic gliomas, we analyzed whole genome mRNA expression profiling of four independent datasets. Univariate Cox regression, linear risk score formula and receiver operating characteristic (ROC) curve were applied to derive a gene signature with best prognostic performance. The corresponding clinical and molecular information were further analyzed for interpretation of the different prognosis and the independence of the signature. Gene ontology (GO), Gene Set Variation Analysis (GSVA) and Gene Set Enrichment Analysis (GSEA) were performed for functional annotation of the differences. We found a three-gene signature, by applying which, the anaplastic gliomas could be divided into low risk and high risk groups. The two groups showed a high concordance with grade II and grade IV gliomas, respectively. The high risk group was more aggressive and complex. The three-gene signature showed diagnostic and prognostic value in anaplastic gliomas.     

Gliomas of the posterior fossa in adults

Infratentorial gliomas are relatively rare tumors compared to their supratentorial counterparts. As such they have not been extensively characterized as a group and are usually excluded from clinical studies. Using our database we aimed to characterize adult gliomas involving the posterior fossa with respect to their clinical behavior and prognostic factors. We reviewed our neurosurgical and neuro-oncological data bases for adult patients diagnosed with gliomas involving the posterior fossa between 1996 and 2010. Of 1,283 glioma patients, 57 patients with gliomas involving the posterior fossa were identified (4.4 %). Tumors were further classified by location as primary brainstem (n = 21) and primary cerebellar (n = 18) tumors. On univariate analysis survival was correlated to tumor grade and KPS. In addition we have identified a unique group of patients (n = 18) with previously diagnosed supratentorial gliomas who subsequently developed noncontiguous secondary infratentorial extension of their tumors with subsequent rapid clinical deterioration. Gliomas of the posterior fossa comprise a heterogeneous group of tumors. Histological grade of the tumor was found to be the main prognostic factor. Survival of primary cerebellar gliomas is comparable to supra-tentorial gliomas, while brainstem gliomas in adults fare better than in the pediatric population. Secondary extension of supratentorial gliomas to the posterior fossa signifies a grave prognosis.     

EGF-R and PDGF-R, but not bcl-2, overexpression predict overall survival in patients with low-grade astrocytomas

BACKGROUND AND OBJECTIVES: Therapy of malignant glioma tumors is based on histology and clinical factors. However, comparable lesions may correspond with important prognostic differences. Our purpose was to analyze retrospectively the prognostic input of platelet-derived growth factor receptor (PDGF-R), epidermal growth factor (EGF-R), and bcl-2 expression in 103 malignant gliomas from uniformly treated patients. METHODS: The expression of the antigens was analyzed by immunohistochemistry (IHC). Prognostic evaluation was performed with the multivariate proportional hazards model. The follow-up period lasted 19 (5-122) months for survivors. RESULTS: We observed that almost 50% of gliomas showed high expression of PDGF-R, while a lower expression of EGF-R and bcl-2 was found. No association between the main prognostic factors in malignant glioma (sex, age, histological grade, and Karnofsky score) and the labeling index (LI) of these antigens was observed. We found that only PDGF-R and EGF-R overexpression were associated with a shorter survival in patients with World Health Organization (WHO) II astrocytomas, being both associations independent of known prognostic factors, as shown by Cox model. Besides, we confirmed other authors' results that high histological grade and low performance score were associated with worse prognosis. CONCLUSIONS: PDGF-R and EGF-R expression could be relevant in determining the prognosis of low-grade astrocytomas (LGAs) and in providing a more objective mechanism for their classification.     

脑胶质瘤组织中Survivin细胞核表达与预后的关系

背景与目的:凋亡抑制蛋白Survivin与肿瘤的侵袭、放化疗抵抗及预后不良有关。Survivin蛋白具有细胞核和细胞浆两种表达形式;最新研究显示survivin细胞核表达对判断肿瘤的预后可能有更重要的意义。本研究旨在探讨脑胶质瘤中Survivin细胞核表达与肿瘤临床病理学特征及预后的相关性。方法:应用免疫组织化学方法和组织芯片技术,检测Survivin在88例胶质瘤组织中的核表达情况,结合临床资料进行统计学分析。结果:88例胶质瘤中,有24例(27.3%)出现Survivin细胞核阳性表达,其中病理Ⅰ～Ⅱ级和Ⅲ～Ⅳ级胶质瘤中的阳性率分别为12.1%(4/33)和36.4%(20/55)(P=0.013),而Survivin细胞核表达与患者的年龄(P=0.053)、性别(P=0.376)、治疗前卡氏评分(Karnofskyperformancestatus,KPS)(P=0.486)以及临床分期(P=0.359)均不相关。Survivin细胞核表达阳性组与阴性组的5年总生存率分别为22.7%、47.7%(P=0.005),3年无瘤生存率为分别为13.7%、39.5%(P=0.015),Survivin细胞核高表达组的中位生存时间为14.9个月,低表达组为20.2个月(P=0.089)。结论:Survivin细胞核表达与胶质瘤的病理学分级有关,而且是胶质瘤预后的不利因素。     

Efficacy of stereotactic radiosurgery as a salvage treatment for recurrent malignant gliomas

BACKGROUND: The objective of this prospective cohort study was to determine the efficacy of stereotactic radiosurgery (SRS) as a salvage treatment in patients with recurrent malignant gliomas. METHODS: Between January 2000 and December 2006, 114 consecutive patients were treated with SRS as a salvage treatment for recurrent malignant gliomas at a single institution. Clinical outcome and its prognostic factors were analyzed and compared with the historical control group who were treated at the same institution between 1995 and 1999. RESULTS: The median overall survival from the time of diagnosis was 37.5 months (95% confidence interval [95% CI], 11.7-63.2 months) for patients with grade 3 gliomas (according to World Health Organization criteria) and was 23 months (95% CI, 16.2-29.3 months) for patients with glioblastomas. The median progression-free survival after SRS was 8.6 months (95% CI, 1.1-16.2 months) for patients with grade 3 gliomas and 4.6 months for patients with glioblastomas (95% CI, 4.0-5.2 months). With regard to treatment-related complications, radiation-induced necrosis was observed in 22 of 114 patients (24.4%). Compared with this historic control group, SRS significantly prolonged survival as a salvage treatment in patients with recurrent glioblastomas (23 months vs 12 months; P < .0001), but it was not found to provide a significant surgical benefit in patients with recurrent grade 3 gliomas (37.5 months vs 26 months; P = .789). On univariate analysis of prognostic factors, tumor volume (<10 mL) and low histologic grade were found to significantly influence better survival (P = .009 and P = .041, respectively). CONCLUSIONS: SRS is a safe and effective modality in selected patients with recurrent small-sized glioblastomas. However, the efficacy of SRS for recurrent grade 3 gliomas needs to be further evaluated in well-designed clinical studies.     

Overexpression of a disintegrin and metalloprotease 8 in human gliomas is implicated in tumor progression and prognosis

A disintegrin and metalloprotease 8 (ADAM8) has been shown to be expressed in various cancer types, and its expression was associated with advanced progression of several tumors. However, little is known about ADAM8 in human gliomas. Therefore, we here evaluated the correlation of ADAM8 expression with the clinicopathological features and prognosis in the patients with gliomas. Immunohistochemistry and western blot were used to investigate the expression of ADAM8 protein, respectively, in 128 patients with gliomas. The expression levels of ADAM8 in glioma tissues were significantly higher (P = 0.002) than those in non-neoplastic brain tissues according to the immunohistochemistry analysis. In addition, a high level of ADAM8 expression was significantly more common in glioma tissues with advanced grade than those with low grade (P = 0.01), which were in line with the results of western blot analysis (P = 0.01). Moreover, the increased expression of ADAM8 was significantly correlated with low Karnofsky performance score (KPS) (P = 0.008), frequent intra-tumor necrosis (P = 0.01), and poor overall survival (P = 0.008). Furthermore, multivariate analysis identified the expression levels of ADAM8 (P = 0.01) and intra-tumor necrosis (P = 0.03) to be independent prognostic factors. These findings suggest for the first time that ADAM8 is frequently overexpressed in human gliomas and is closely associated with poor clinical outcome.