脑胶质瘤的放射治疗进展

 脑胶质瘤治疗以外科手术为主，由于肿瘤侵蚀性强，与脑组织无明显分界，手术难以彻底切除，易复发，生存期短，死亡率高。因此，术后辅助放射治疗占有重要地位。而脑胶质瘤的预后受患者的年龄、Karnofsky评分、病理类型和侵犯范围等因素的影响，其疗效仍不理想。为探索脑胶质瘤放射治疗的疗效，近年来放射治疗的新设备、新技术不断改善和进步，为脑胶质瘤的放射治疗提供了条件。主要阐述了高分级与低分级脑胶质瘤放射治疗以及放疗联合化疗的现状和进展。     

高级别脑胶质瘤放疗剂量分割研究现状及进展

高级别脑胶质瘤恶性度高,手术加术后常规放疗及化疗综合治疗是目前标准治疗方案,但疗效仍未见明显改善。研究显示高级别脑胶质瘤对放疗敏感度差,这就需要探索不同放疗分割模式的获益可能,为改善高级别脑胶质瘤患者的预后,近年来不少学者在放射治疗分割方式方面做了大量研究。本文就脑胶质瘤放疗剂量分割现状及其疗效作一总结。     

脑胶质瘤干细胞研究进展

脑胶质瘤是常见的脑原发恶性肿瘤,其治疗主要依据WHO分级;手术切除为首选,术后放疗及放化疗是提高脑胶质瘤生存期的重要手段.低分级脑胶质瘤的治疗效果较好,生存期较长;而高分级患者治疗后的生存期只能以月来描述.脑胶质瘤治疗失败的主要原因是局部复发,而导致复发的重要原因是胶质瘤干细胞未得到有效控制.因此,脑胶质瘤干细胞的鉴别及生物学特性的研究成为近年来国内外学者关注的热点,笔者综述脑胶质瘤干细胞的研究进展.     

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。     

复发性脑胶质瘤患者再手术治疗的预后因素分析

目的 探讨复发性脑胶质瘤患者再手术治疗的预后因素。方法 回顾性分析80例行再手术治疗的复发性脑胶质瘤患者临床资料,并对患者进行1年左右的随访,记录其生存情况。结果 80例脑胶质瘤患者再手术后1年生存率为71.25%(57/80),中位生存时间为15个月。与死亡组比较,存活组再手术前KPS评分、病理Ⅰ～Ⅱ级和全切手术者占比均较高(P<0.05),经Cox回归分析发现再手术前KPS评分、病理分级和手术切除范围是复发性脑胶质瘤患者再手术预后的影响因素(P<0.05)。ROC曲线发现,再手术前KPS评分、病理分级和手术切除范围对预测患者再手术预后均具有一定价值,3项联合时预测效能最高。结论 复发性脑胶质瘤患者再手术治疗后的1年生存率受再手术切除范围、术前KPS评分和病理分级的影响,可将其作为预测患者再手术后预后的因子。     

磷酸酯酶与张力蛋白同源物、Ki-67在脑胶质瘤中的表达及与患者预后的关系

目的 探讨磷酸酯酶与张力蛋白同源物（PTEN）、Ki-67在脑胶质瘤中的表达及与患者预后的关系。方法 选取152例脑胶质瘤患者的肿瘤组织及相应癌旁组织,免疫组化法检测PTEN、Ki-67表达情况。随访1年,记录患者的预后情况,脑胶质瘤患者预后影响因素采用多元Logistic回归分析。结果 脑胶质瘤患者肿瘤组织中Ki-67的阳性表达率明显高于癌旁组织,PTEN的阳性表达率明显低于癌旁组织,世界卫生组织（WHO）分级为Ⅲ～Ⅳ级脑胶质瘤患者肿瘤组织中Ki-67的阳性表达率明显高于Ⅰ～Ⅱ级患者,PTEN的阳性表达率明显低于Ⅰ～Ⅱ级患者,差异均有统计学意义（P﹤0.01）。随访1年,152例脑胶质瘤患者中,预后不良47例,预后良好105例,预后不良和预后良好脑胶质瘤患者WHO分级、Ki-67表达情况、PTEN表达情况比较,差异均有统计学意义（P﹤0.01）。多元Logistic回归分析结果显示,WHO分级为Ⅲ～Ⅳ级、Ki-67阳性表达、PTEN阴性表达均为脑胶质瘤患者预后的独立危险因素（P﹤0.01）。结论 脑胶质瘤患者肿瘤组织中Ki-67的阳性表达率较高、PTEN的阳性表达率较低,WHO分级为...     

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。     

ITGA5在胶质瘤组织中的表达及临床意义

目的:探究整合素α5（integrinα5,ITGA5）在脑胶质瘤组织中的表达及其与临床病理参数和预后的关系。方法:比较TCGA数据库中胶质瘤和正常脑组织ITGA5的表达差异和临床预后的生物学信息。收集临沂市人民医院54例脑胶质瘤手术患者的脑胶质瘤组织标本和临床资料,以及20例脑外伤患者颅内减压后的脑组织标本。以外伤后的脑组织为对照,采用免疫组织化学染色法与蛋白质印迹法检测ITGA5蛋白在胶质瘤中的表达。采用统计学方法研究ITGA5表达水平与临床病理参数的相关性。通过绘制生存曲线,比较ITGA5高表达和低表达患者的预后差异。结果:TCGA数据库中ITGA5在LGG与GBM中的表达均有显著差异（P＜0.001）,表达量随着胶质瘤WHO病理分级的升高而增加,且与患者的不良预后相关。ITGA5在胶质瘤组织中的高表达率为59.2%（32/54）,外伤后脑组织中的高表达率为5.0%（1/20）,两者之间的差异有统计学意义（P＜0.05）。ITGA5在胶质瘤组织中的表达与WHO分级、Ki-67和p53基因型相关（P＜0.05）,而与年龄、性别和肿瘤部位无关（P＞0.05）。ITGA5高表达胶质瘤患者的生存时间显著低于ITGA5低表达胶质瘤患者（P＜0.05）。结论:ITGA5在胶质瘤组织中的表达增加,且ITGA5的表达与胶质瘤病理分级和患者生存密切相关。     

术前预后营养指数在脑胶质瘤患者术后预后评估中的应用

目的:探讨术前预后营养指数(prognostic nutrition index,PNI)在脑胶质瘤患者术后临床预后中的应用。方法:收集2011年1月至2017年6月四川省大邑县人民医院神经外科手术治疗且经术后病理确诊的131例初发脑胶质瘤患者的临床资料及术后生存资料,采用ROC曲线分析获得PNI的最佳临界值,依据该最佳临界值将患者分为高PNI值组及低PNI值组,采用卡方检验比较两组临床病理学特征,采用Cox比例风险回归模型分析PNI与胶质瘤患者术后临床预后的关系。结果:131例脑胶质瘤患者术后中位总生存时间（overall survival,OS）为23个月,95%CI:9.736~36.264个月,术后1年、2年、3年、5年生存率分别为76.3%、52.0%、43.0%、33.5%。ROC曲线分析,PNI的最佳临界值为48.5。低PNI值组中年龄≥45岁、行非全切手术和较低级别肿瘤分级所占的比例较高PNI值组更高(P＜0.05)。多因素Cox回归分析显示,肿瘤分级、PNI值是影响脑胶质瘤患者术后预后的独立影响因素。结论:PNI值为脑胶质瘤患者预后的独立危险因素,较低的PNI水平预示着较差的预后。PNI值可用于初步判断脑胶质瘤患者的预后。     

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。     

神经导航显微手术辅以光动力疗法治疗脑胶质瘤

背景与目的:神经导航引导下显微手术和光动力疗法均是治疗脑胶质瘤的新技术,本文探讨此二种方法有机结合治疗脑胶质瘤的效果。方法:在12例脑胶质瘤手术中,先应用GE350磁导航系统引导显微镜下切除肿瘤,再应用波长为630nm半导体激光器直接照射肿瘤残腔(200J/cm2),在照光前3小时静脉滴注血卟啉单甲醚5mg/kg。结果:术后近期效果满意,无严重神经功能障碍并发症。1例于术后2个月出现脑水肿,给予对症处理后恢复,无治疗相关死亡。结论:神经导航引导下显微手术和光动力疗法有机结合治疗脑胶质瘤是可行的。     

恶性胶质瘤靶向治疗研究进展

目的 恶性胶质瘤是一种最常见的原发恶性脑肿瘤,是癌症治疗中最具挑战性疾病之一.因为手术切除后肿瘤易复发和治疗抵抗性,患者预后普遍较差.胶质瘤的分子靶向治疗正逐渐引起广泛关注.本研究总结恶性胶质瘤发病相关的分子病理改变和靶向药物的临床应用与研究进展.方法 采用PubMed文献检索系统,以“恶性胶质瘤”和“分子靶向治疗”为关键词,检索2007-01-01-2015-12-31的相关文献.纳入标准:(1)与恶性胶质瘤分子靶向通路相关的文献;(2)与恶性胶质瘤抗血管生成治疗相关的文献;(3)与恶性胶质瘤分子靶向药物的Ⅰ期及Ⅱ期临床研究相关的文献;(4)与恶性胶质瘤分子靶向耐药相关的文献.根据纳入标准分析文献43篇.结果 胶质瘤靶向治疗方向主要集中在RTK/RAS/PI3K通路、促血管生成通路和一些其他重要的细胞内信号转导通路.然而,一些因素如信号通路之间的串扰、瘤内异质性和胶质瘤干细胞的治疗抵抗性限制了单一药物的活性.各种分子靶向药物单药治疗未能表现出更好的生存获益,还需与其他治疗方法联合应用.目前对于恶性胶质瘤患者多靶点激酶抑制剂治疗的研究还处于起始阶段.结论 分子靶向药物在恶性胶质瘤的治疗中具有重要临床意义和应用潜力,但由于胶质瘤的复杂的分子生物学特性,分子靶向治疗面临诸多挑战,还需进一步探索与研究.     

胶质瘤能量代谢与放射敏感度的研究进展

放射治疗是胶质瘤重要的辅助治疗手段,尽管近年来胶质瘤的综合治疗取得了一定进展,然而其预后仍然较差,如何提高胶质瘤的放射敏感度是当前胶质瘤研究的热点之一.胶质瘤能量代谢改变促进了其恶性进展及放化疗抵抗,然而其确切机制仍然不清,该文就胶质瘤能量代谢改变及其与胶质瘤放射敏感度的研究进展进行综述,旨在为进一步提高胶质瘤放射敏感...     

Copper/Zinc Superoxide Dismutase,Nuclear DNA Content,and Progression in Human Gliomas

To our knowledge, there have been no previous reports regarding the immunohistochemistry and image cytometry to demonstrate elevated Copper/zinc superoxide dismutase (Cu/Zn SOD) expression and numbers of the clonal cells in human gliomas. In 30 well-studied patients with gliomas, immunoreactivity for Cu/Zn SOD and cytometric evidence of DNA ploidy in the G2M cell cycle phase were evaluated from routinely prepared tissue blocks.Cu/Zn SOD positive tumor cells were shown in 8 of 13 glioblastomas (mean quantitative immunoreactivity SOD score; 1), 3 of 8 anaplastic gliomas (score; 0.6), and none of 9 low-grade gliomas. The differences in SOD score was not significant. In hypertetraploid glioblastomas, time to progression was shorter than for hypertetraploid of anaplastic gliomas, while SOD scores were not significantly different. The same relationship held for tetraploid specimens. Considering variables in combination, hypertetraploid gliomas with high SOD immunoreactivity showed a significantly short time to progression (p<0.05) (1–5 months after radiotherapy and chemotherapy) compared with hypertetraploid, low-SOD immunoreactivity gliomas or tetraploid, low-SOD immunoreactivity gliomas.The tumor cells with high SOD activity also tended to be resistant for radiotherapy and anticancer drugs. Those results were suggested that the high grade glioma with a single clone and low SOD activity were effective for radiotherapy associated with oxidative stress, and that the high grade gliomas with more than two clones and high SOD activity were very less effective for same therapy.Cu/Zn SOD activity and the degree of the clonality in human gliomas should be very important factors influencing a choice of oxidative cytotoxic treatment.     

Molecular analysis of CDKN2 (p16) in gliomas associated with clinical data

We analyzed alterations in CDKN2 in gliomas from an ethically mixed population and correlated the results with patients clinical data. We screened for methylation at CDKN2 and for microsatellite instability (MSI) and loss of heterozygosity (LOH) in the region 9p21-22 using 4 markers. We found: 3/30 (10%) cases with CDKN2-methylated gliomas; an average of 4% of MSI; and 24.5% of LOH in the region 9p21-22. Methylation of CDKN2 was only detected in patients showing high-grade gliomas with short survival. MSI and LOH in the region 9p21-22 were detected in patients showing high-grade gliomas with short survival and in one patient with a recurrent low-grade astrocytoma grade II who died from the disease after 3 years, indicating that such alterations represent poor prognosis.     

MicroRNAs involved in chemo- and radioresistance of high-grade gliomas

High-grade gliomas (HGGs) are malignant primary brain tumors of glial cell origin. Despite optimal course of treatment, including maximal surgical resection followed by adjuvant chemo- and/or radiotherapy, the prognosis still remains poor. The main reason is the commonly occurring chemo- and radioresistance of these tumors. In recent years, several signaling pathways, especially PI3K/AKT and ATM/CHK2/p53, have been linked to the resistance of gliomas. Moreover, additional studies have shown that these pathways are significantly regulated by microRNAs (miRNAs), short endogenous RNA molecules that modulate gene expression and control many biological processes including apoptosis, proliferation, cell cycle, invasivity, and angiogenesis. MiRNAs are not only highly deregulated in gliomas, their expression signatures have also been shown to predict prognosis and therapy response. Therefore, they present promising biomarkers and therapeutic targets that might overcome the resistance to treatment and improve prognosis of glioma patients. In this review, we summarize the current knowledge of the functional role of miRNAs in gliomas resistance to chemo- and radiotherapy.     

Phase II study of fotemustine in recurrent supratentorial malignant gliomas

38 adults with recurrent supratentorial malignant gliomas, including glioblastoma multiforme (21), anaplastic astrocytomas (9), probably transformed low-grade astrocytomas (6), pinealoblastoma (1) and non-metastatic tumour of unknown histology (1), were treated with fotemustine 100 mg/m² intravenously every week for 3 consecutive weeks followed by a 5-week rest period. Maintenance treatment consisted of one infusion every 3 weeks. Patients were divided into three groups according to treatment effect. 10 objective responses (26%) with a median time without progression of 32.7 weeks, 18 stabilisations (47%) and 10 failures (26%) were observed. Pathological findings of the initial primary tumour and neurological functional status were unequally distributed in these groups. Haematological and liver toxicities were mild, delayed, transient and reversible. Thrombocytopenia and leukopenia were more frequent (30%) in patients treated with prior chemotherapy. Fotemustine is a well tolerated active drug in recurrent malignant gliomas with an original and short treatment schedule.     

18F-FDOPA and 18F-FLT positron emission tomography parametric response maps predict response in recurrent malignant gliomas treated with bevacizumab

The current study examined the use of voxel-wise changes in (18)F-FDOPA and (18)F-FLT PET uptake, referred to as parametric response maps (PRMs), to determine whether they were predictive of response to bevacizumab in patients with recurrent malignant gliomas. Twenty-four patients with recurrent malignant gliomas who underwent bevacizumab treatment were analyzed. Patients had MR and PET images acquired before and at 2 time points after bevacizumab treatment. PRMs were created by examining the percentage change in tracer uptake between time points in each image voxel. Voxel-wise increase in PET uptake in areas of pretreatment contrast enhancement defined by MRI stratified 3-month progression-free survival (PFS) and 6-month overall survival (OS) according to receiver-operating characteristic curve analysis. A decrease in PET tracer uptake was associated with longer PFS and OS, whereas an increase in PET uptake was associated with short PFS and OS. The volume fraction of increased (18)F-FDOPA PET uptake between the 2 posttreatment time points also stratified long- and short-term PFS and OS (log-rank, P < .05); however, (18)F-FLT uptake did not stratify OS. This study suggests that an increase in FDOPA or FLT PET uptake on PRMs after bevacizumab treatment may be a useful biomarker for predicting PFS and that FDOPA PET PRMs are also predictive of OS in recurrent gliomas treated with bevacizumab.     

Epigenetic dysregulation in glioma

Given that treatment options for patients with glioblastoma are limited, much effort has been made to clarify the underlying mechanisms of gliomagenesis. Recent genome‐wide genomic and epigenomic analyses have revealed that mutations in epigenetic modifiers occur frequently in gliomas and that dysregulation of epigenetic mechanisms is closely associated with glioma formation. Given that epigenetic changes are reversible, understanding the epigenetic abnormalities that arise in gliomagenesis might be key to developing more effective treatment strategies for glioma. In this review, we focus on the recent advancements in epigenetic research with respect to gliomas, consider how epigenetic mechanisms dynamically regulate tumor cells, including the cancer stem cell population, and discuss perspectives and challenges for glioma treatment in the near future.     

Dendritic cell-based immunotherapy of malignant gliomas

The failure of conventional treatment modalities for gliomas, in spite of tremendous progress in research in the past two decades, has led to increasing interest in alternative treatment strategies, including immunotherapy. It has become evident that vaccination with dendritic cells (DC), designed to express tumor antigens, is a potent strategy to elicit anti-tumor immune response in both pre-clinical and clinical settings. Various methods have been applied in order to induce DC to express tumor antigens including: pulsing with isolated tumor peptides or whole tumor lysate; fusion with tumor cells; and pulsing with apoptotic tumor cells. Herein, we review the recent progress in DC biology with regard to tumor immunity and discuss current DC-based strategies and future prospects in immunotherapy for malignant gliomas.