多形性脑胶质母细胞瘤化疗对预后的评价

多形性胶质母细胞瘤（glioblastoma multiforme,GBM）,按Kernohan分类属于星形细胞瘤Ⅲ～Ⅳ级,WHO2007年中枢神经系统肿瘤分类标准将其归类为星形细胞瘤Ⅳ级,占中枢神经系统恶性肿瘤的25％。该病男性发病率高于女性,具有家族聚集倾向。以往研究认为该病平均发病年龄为60岁,但近些年患者呈现出年轻化的趋势。     

多形性胶质母细胞瘤基因治疗的研究进展

基因治疗有望改变胶质母细胞瘤临床疗效。目前在导入自杀基因、修复或导入抑癌基因、肿瘤免疫基因治疗、血管生成抑制基因治疗、溶瘤病毒治疗等基因治疗策略方面展开了广泛的研究。但因存在GBM发病机制不明确,基因载体、基因转染调控技术不完善,安全性等问题。目前尚没有基因治疗在临床中取得良好效果的报道。     

多发性多形性胶质母细胞瘤

病例介绍。患男，53岁、主因1日内癫痫发作3次入院．服用镇静药好转。神经系统查体无阳性体征。     

颅内多发多形性胶质母细胞瘤3例报告

目的探讨颅内多发多形性胶质母细胞瘤的临床特点.方法对3例多发多形性胶质母细胞瘤病人行手术治疗,术后给予放疗等辅助治疗,结合文献分析其影像学特点,总结临床经验.结果多发多形性胶质母细胞瘤临床特点为:病程短,病情进展迅速,容易误诊.CT上常表现为脑实质内多发病灶,形态不规则,边界不清,伴有程度不一的瘤周水肿和占位效应.MRI检查示病灶T1W像上呈低信号,T2W为高信号,边界不清,但在肿瘤增殖旺盛处,T1W为高信号,T2W为低信号.结论术前对该病作出正确诊断,有助予治疗方案的设计及治疗效果的评估.     

原发性胶质母细胞瘤预后危险因素分析

目的 探讨原发性胶质母细胞瘤预后的危险因素。方法 收集1994~2014年收治的69例原发性胶质母细胞瘤的临床资料及肿瘤标本,以死亡作为随访终点,采用Cox比例风险模型筛选生存期危险因素。结果 本组随访时间为3.0~25.5个月,中位随访时间为11.0个月。单因素分析结果 显示,年龄≥50岁、肿瘤未全切、染色体1p/19q未缺失、异柠檬酸脱氢酶1（IDH1）未突变为生存期危险因素（P <0.05）;Cox多因素分析结果 显示,年龄≥50岁及染色体1p/19q未缺失为独立危险因素（P <0.05）。将危险因素进行量化并分为高、中、低危组,中位无进展生存期分别为3.5、6.5、9.0个月,中位总体生存期为6.5、11.0、15.0个月;3组中位无进展生存期和中位总体生存期均有显著差异（P <0.05）。结论 年龄≥50岁、肿瘤未全切、1p/19q未缺失和IDH1未突变,是影响原发性GBM生存期的危险因素;将GBM生存期危险因素量化后进行分组,可为GBM个体化治疗提供一定帮助。     

影响胶质母细胞瘤患者预后的多因素分析

目的 探讨影响胶质母细胞瘤患者预后的临床因素.方法 回顾2008年1月至2013年1月于南方医科大学南方医院行显微手术治疗的198例原发胶质母细胞瘤患者的临床资料,对性别、年龄、起病至就诊时间、术前有无癫痫发作、术前KPS评分、肿瘤部位、肿瘤直径、肿瘤是否发生囊变、手术切除程度、术后是否行同步放化疗、术后是否存在颅内感染共11项因素进行生存分析.结果 单因素分析结果示术前有无癫痫发作、肿瘤部位、术前KPS评分、手术切除程度、术后是否同步放化疗、术后是否存在颅内感染对胶质母细胞瘤患者的预后有影响(P＜0.05);多因素分析结果示手术切除程度、肿瘤部位、术前KPS评分、术后是否同步放化疗、术后是否颅内感染具有统计学意义(P＜0.05).结论 手术切除程度、肿瘤部位、术前KPS评分、术后同步放化疗是影响胶质母细胞瘤患者的主要预后因素,其中手术切除程度是最重要的预后因素;而术后颅内感染的患者生存时间延长,可能与感染诱导的肿瘤免疫有关.     

岛叶胶质母细胞瘤的临床特征和预后影响因素分析

目的探讨岛叶胶质母细胞瘤的临床特征和影响预后的临床因素。方法回顾性分析2006年7月至2013年6月中国脑胶质瘤基因组图谱计划(CGGA)数据库中44例岛叶胶质母细胞瘤患者的临床资料。所有患者均行肿瘤切除术,术后27例接受放、化疗联合治疗,另17例未接受。总结所有患者的临床特征,包括是否存在癫痫发作史、异柠檬酸脱氢酶1(IDH1)突变、O6-甲基鸟嘌呤-DNA-甲基转移酶(MGMT)甲基化、肿瘤强化情况及临床分型等。采用Kaplan-Meier法分析所有患者的无进展生存期(PFS)和总生存期(OS)。进一步采用多因素Cox回归分析方法探讨影响患者PFS和OS的临床因素。结果44例患者中,33例(75.0%)存在癫痫发作史,11例(25.0%)为IDH1突变型,19例(43.2%)存在MGMT甲基化,42例(95.5%)存在肿瘤强化。Yasargil分型:2例为3A型,27例为3B型,15例为5A/B型;Saito分型:2例局限于岛叶皮质内,9例经前环岛沟向额叶侵袭,16例经下环岛沟向颞叶侵袭,17例经2个以上环岛沟向多方侵袭;Moshe分型:35例对豆纹动脉形成包绕或侵袭,余9例未侵袭;壳核分型:38例对壳核不同程度的侵袭,余6例未累及。Kaplan-Meier法分析结果显示,所有患者的中位PFS为278 d,中位OS为435 d。多因素Cox回归分析结果显示,肿瘤体积小于中位数(HR=0.390,95%CI:0.189~0.802,P=0.011)、IDH1突变(HR=0.391,95%CI:0.175~0.876,P=0.023)及术后放、化疗联合治疗(HR=0.346,95%CI:0.162~0.738,P=0.006)是影响患者PFS的独立保护因素;而MGMT甲基化(HR=0.371,95%CI:0.181~0.758,P=0.007)、肿瘤切除程度≥90%(HR=0.412,95%CI:0.194~0.875,P=0.021)及术后接受放、化疗联合治疗(HR=0.347,95%CI:0.170~0.708,P=0.004)是影响患者OS的独立保护因素。结论岛叶胶质母细胞瘤对脑深部重要的神经血管结构具有很强的侵袭性,手术切除难度大,预后差;最大程度切除肿瘤并规范放、化疗可改善患者的预后。     

脊髓多形性胶质母细胞瘤椎管内转移播种一例

患者男,19岁。胸腰痛6个月,加重伴双下肢无力1周入院。查体:T7以下浅感觉减退,L2以下感觉消失,右下肢肌力Ⅰ级,左下肢肌力Ⅲ级,L4～5椎间隙腰穿:压力300cmH2O,淡黄色脑脊液,奎肯试验椎管不通。MRI示脊髓胸段(T5～7)弥漫性增粗,其内信号不均,T12椎体以下1/3水平状横断影,分割椎管内蛛网膜下腔为略低的信号改变,下部蛛网膜下腔高信号内可见多发小圆形中等信号异常占位病变,附着在马尾及硬脊膜上,蛛网膜下腔远端骶管可见一直径3cm中等信号软组织占位影,形成充盈缺损,液体梗阻平面以上蛛网膜下腔内信号不均匀,冠状位可见多发软组织占位,其…     

原发性脊髓胶质母细胞瘤的临床特点及预后因素分析

目的 探讨原发性脊髓胶质母细胞瘤的临床特点及其预后影响因素.方法 回顾性纳入2008年1月至2015年12月四川大学华西医院神经外科行手术治疗的14例原发性脊髓胶质母细胞瘤患者,总结其临床特征并分析影响患者预后的因素.结果 14例患者中,近全切除4例,部分切除5例,活检5例.9例术后接受放、化疗,3例仅行化疗,2例未行放、化疗.中位随访时间为15个月（5-26个月）,1年和2年生存率分别为79％ （11/14）和7％（1/14）.中位总生存期（OS）为15个月,中位无进展生存期（PFS）为8个月.单因素Log-rank分析显示,年龄以及是否进行术后放疗均为OS和PFS的影响因素（均P〈0.05）;术前Karnofsky功能状态评分（KPS）为OS的影响因素（P=0.033）,但并非PFS的影响因素（P=0.106）;性别、肿瘤切除程度以及病理学结果均非OS及PFS的影响因素（均P〉0.05）.单因素Cox回归分析显示,年龄、术后是否放疗均影响OS和PFS（均P〈0.05）;而术前KPS仅影响OS（P=0.046）.多因素Cox逐步回归分析显示,术后是否放疗为影响OS和PFS的惟一因素（均P 〈0.05）,放疗者较未放疗者的生存期长.结论 原发性脊髓胶质母细胞瘤临床罕见且预后极差.肿瘤切除程度与患者的预后无关,术后联合放疗能在一定程度上延长患者的生存期.     

贝伐单抗在多形性胶质母细胞瘤中的研究进展

胶质瘤来源于神经上皮组织,是颅内最常见的原发性肿瘤,约占颅内肿瘤的40%。世界卫生组织(WHO)根据病理学和临床标准将胶质瘤分为I～IV级,其中,多形性胶质母细胞瘤(glioblastoma multiforme,GBM)约占成人胶质瘤的50%,恶性程度极高,预后极差,即使经过手术切除以及术后标准放化疗,其中位生存期也仅为14.6个月[1]。这可能与GBM本身     

Overall survival,prognostic factors,and repeated surgery in a consecutive series of 516 patients with glioblastoma multiforme

Helseth R, Helseth E, Johannesen TB, Langberg CW, Lote K, Rønning P, Scheie D, Vik A, Meling TR. Overall survival, prognostic factors, and repeated surgery in a consecutive series of 516 patients with glioblastoma multiforme.
Acta Neurol Scand: 122: 159–167.
© 2010 The Authors Journal compilation © 2010 Blackwell Munksgaard. Objectives – To study overall survival (OS), prognostic factors, and repeated surgery in glioblastoma multiforme (GBM). Material and methods– Retrospective study of 516 consecutive adult patients who underwent primary surgery for a GBM in year 2003–2008. Results – Median age at primary surgery was 63.7 years (range 18.0–88.0). Median OS was 9.9 months. Age >60 years, poor preoperative ECOG score, bilateral tumor, biopsy rather than resection, and no temozolomide chemoradiotherapy were negative risk factors. Repeat surgery was performed in 65 patients (13%). Median time between first and second surgery was 7 months. Indications for second surgery were increasing neurological deficits (35.4%), raised ICP (33.8%), asymptomatic but reoperated because of tumor progression verified on MRI (20.0%), and epileptic seizures (11%). Patients who underwent repeated surgery had longer OS; 18.4 months vs 8.6 months (P < 0.001). Conclusions – OS for adult GBM patients was 9.9 months. Negative prognostic factors were increasing age, poor neurological function, bilateral tumor involvement, biopsy instead of resection, and RT alone compared to temozolomide chemoradiotherapy. Our rate of repeated surgery for GBM was 13% and the main indications for second surgery were raised ICP and increasing neurological deficits. In a carefully selected group of patients, repeat surgery significantly prolongs OS.     

Carbonic anhydrase IX is a prognostic biomarker in glioblastoma multiforme

The identification of prognostic factors in patients with glioblastoma multiforme (GBM) represents an area of increasing interest. Carbonic anhydrase IX (CA‐IX), a hypoxia marker, correlates with tumor progression in a variety of human cancers. However, the role of CA‐IX in GBM remains largely unknown. In the present study, we evaluated the prognostic role of CA‐IX in GBM patients. In total, 66 consecutive patients with GBM who received concomitant chemoradiotherapy and adjuvant chemotherapy with temozolomide were retrospectively reviewed, and all patients received temozolomide chemotherapy for at least 3 months. Kaplan–Meier curves and log‐rank tests were used for analysis of progression‐free survival (PFS) and overall survival (OS), and a multivariate Cox proportional hazard model was employed to identify factors with an independent effect on survival. The median OS was longer in patients with low levels of CA‐IX expression (18 months) compared to patients overexpressing CA‐IX (9 months) (P = 0.004). There was not a statistically significant difference in median PFS (3.5 vs. 8 months, P = 0.054) between patients with high or low levels of CA‐IX expression. In multivariate analysis, the variables that were identified as significant prognostic factors for OS were preoperative Karnofsky performance scale score (KPS) (hazard ratio (HR), 3.703; P = 0.001), CA‐IX overexpression (HR, 1.967; P = 0.019), and incomplete adjuvant temozolomide treatment (HR, 2.241; P = 0.003) and gross‐total resection (HR, 1.956; P = 0.034). Our findings indicated that CA‐IX may be a potential prognostic biomarker in the treatment of GBM.     

胶质母细胞瘤患者自噬相关mRNA与lncRNA的预后判断价值

目的 分别构建由自噬相关基因（ATG）与自噬相关lncRNA（ATL）构成的预后模型,预测胶质母细胞瘤（GBM）患者的预后情况,为其个性化诊疗与基础研究提供依据。方法 利用TCGA数据库中GBM的测序与临床数据,通过单因素Cox回归分析筛选差异表达且具备预后价值的ATG与ATL,之后通过多因素Cox回归分析分别构建预后模型,根据模型计算患者风险值并验证其有效性。结果 GBM组织相较正常组织共筛选到72个差异表达的ATG（上调53个,下调19个）和170个ATL（上调102个;下调68个）,单因素Cox回归分析筛选到16个与患者预后相关的ATG和22个ATL,多因素Cox回归分析分别纳入3个ATG与8个ATL构建预后模型。生存曲线显示在2个模型中高风险组生存率远低于低风险组,受试者工作特性曲线证明2个模型均具有较好的预测能力。结论 所构建的2个预后模型可有效预测患者生存情况,并提供个性化诊疗与基础研究参考。     

Nucleolar organizer regions and post–operative survival in glioblastoma multiforme

Counts of argyrophil nucleolar organizer regions (AgNORs) have been proposed as a method of assessing tumour growth rate. AgNOR counts have been shown to correlate with histological grade in glial and some non-glial tumours but few studies have included data relating to clinical outcome. We have examined the relationship between tumour AgNOR counts and postoperative survival in a retrospective study of 54 patients with glioblastoma multiforme. The mean number of AgNORs per nucleus varied from 1.7 to 10.8 in biopsies from different patients and correlated with mitotic rate (P less than 0.01) but not with post-operative survival, which ranged from 2 days to 54 months with four patients still alive. AgNOR counts were inversely related to patient age (P less than 0.01) and older patients tended to survive for shorter periods (P less than 0.05). Although AgNOR counts are related to the rate of tumour cell division, they are not useful for predicting the post-operative survival of patients with glioblastoma multiforme.     

Quality-adjusted survival after tumor resection and/or radiation therapy for elderly patients with glioblastoma multiforme

Objective: Prognostic factors are poorly defined for the elderly subpopulation with glioblastoma multiforme and have been exclusively related to conventional survival analysis. In this study an additional quality adjusted survival analysis (QAS) was performed. The prognostic evaluation of both survival- and QAS data after standard treatment were checked for concordant/discordant findings. Their usefulness for estimation of treatment effects and treatment strategies was then evaluated. Methods: 123 patients ≥ 65 years of age with a supratentorial, de novo glioblastoma were included in the current retrospective report. Microsurgery plus radiation therapy (planned tumor dose: 60 Gy) was performed in 58 patients, and radiation therapy alone after stereotactic biopsy (planned tumor dose: 60 Gy) in 65 patients. The functional status of each patient was scored when joining the study and at every follow-up using 15 selected neurological signs and symptoms (NSSs). Gradation of severity of each NSS was performed with subjective weights. Survival time of each patient was adjusted according to any changes in these NSSs to become the Quality Time (Q-TIME). Time intervals spent with side effects of the treatment (TOX) were subtracted from Q-TIME to become the patient's QAS (QAS = Q-TIME–TOX). Prognostic factors for both survival and QAS were obtained from the Cox model. Results: Overall survival and QAS were 24 weeks and 10.5 weeks, respectively. Perioperative morbidity and mortality were 5.2 % and 1.7 % in the surgery group and 1.5 % and 1.5 % in the biopsy group, respectively (p > 0.05). Tumor resection gained favorable prognostic importance for patients with midline shift in terms of both survival and QAS (p < 0.0001). Otherwise, radiation therapy alone was as effective as surgery plus radiation therapy (concordant finding). A pretreatment Karnofsky Score (KPS) < 70 was an unfavorable predictor for QAS (p < 0.002) but not for survival (discordant finding). Median QAS for patients with a pretreatment KPS < 70 was only 10 weeks. Age did not reach prognostic relevance. Conclusion: The dramatic decrease of QAS as compared with survival indicates extremely limited posttreatment improvement and/or rapid deterioration of the neurological score after standard treatment for the older subpopulation with glioblastoma multiforme. Supportive treatment should be considered for patients with a pretreatment KPS < 70. Received: 10 September 2002, Received in revised form: 25 November 2002, Accepted: 2 December 2002 Correspondence to F. W. Kreth, M. D.     

小胶质细胞/巨噬细胞在胶质母细胞瘤中作用的研究进展

胶质母细胞瘤（GBM）是成人最常见的颅内恶性肿瘤,具有极强的侵袭性。此外,由于化疗药物难以通过血脑屏障和胶质母细胞瘤的耐药性,及对放疗敏感性较差等特点,故预后极差。其中肿瘤微环境的改变起到了至关重要的作用,在微环境中胶质瘤相关的小胶质细胞/巨噬细胞（GAMs）的作用正逐渐被重视。GAMs不仅有中枢系统的常驻小胶质细胞,还有来自外周的巨噬细胞。GAMs还有截然不同的两种极化类型,即抑制肿瘤生长的M1表型和促进肿瘤生长的M2表型。并且GAMs不单单和肿瘤细胞具有联系,还与微环境中其他非癌性脑细胞也有互动。该文将从GAMs的来源、极化、与肿瘤微环境中各种细胞间的相互影响阐述其在GBM中的作用,并且从靶向治疗的角度探讨其最新的研究进展。     

Long-term survival of glioblastoma multiforme: importance of histopathological reevaluation

The overall prognosis for patients with glioblastoma multiforme is extremely poor. However, a small proportion of patients enjoy prolonged survival. This study investigated retrospectively the extent to which erroneous histopathological classification may contribute to long-term survival of patients initially diagnosed with “glioblastoma multiforme”. We compared two age- and gender-matched patient groups with different postoperative time to tumor progression (TTP), defined as “short-term” for TTP of less than 6 months (n=54) and “long-term” for TTP of more than 12 months (n=52). Histological specimens of the corresponding tumors, all primarily diagnosed as glioblastome multiforme, were reevaluated according to the current World Health Organization (WHO) classification of central nervous system tumors, with the investigators being blinded to clinical outcome. Among the tumors from short-term TTP patients, one tumor (2%) was reclassified as anaplastic oligoastrocytoma (WHO grade III) while the remaining 53 were confirmed as glioblastoma multiforme. In contrast, 13 tumors (25%) from the long-term TTP patients were reclassified, mostly as anaplastic oligodendroglioma (WHO grade III; n=7) or anaplastic oligoastrocytoma (WHO grade III, n=2), respectively. In addition, three were reclassified as anaplastic astrocytoma (WHO grade III), and one was identified as anaplastic pilocytic astrocytoma (WHO grade III). Our data indicate that a sizable proportion of glioblastoma patients with long-term survival actually carry malignant gliomas with oligodendroglial features. The correct histopathological recognition of these tumors has not only progrostic but also therapeutic implications, since oligodendroglial tumors are more likely to respond favorably to chemotherapy. Received: 9 November 1999, Received in revised form: 13 January 2000, Accepted: 3 February 2000