多形性胶质母细胞瘤预后因素分析

目的 探讨多形性胶质母细胞瘤(GBM)预后相关的临床因素.方法 回顾性分析160例随访资料完整的GBM,采用Kaplan-Meier法计算生存率及进行单因素分析,Log-rank法进行生存率显著性检验,Cox比例风险回归模型作多因素分析.结果 本组病人术后1年、2年、5年生存率分别是65.3％、34.1％、9.1％.单因素分析显示年龄、肿瘤切除程度、治疗方式是影响GBM生存率的因素.多因素分析显示年龄、肿瘤部位、肿瘤切除程度及治疗方式是与GBM预后相关的独立因素.结论 年龄、肿瘤部位、肿瘤切除程度和治疗方式是影响GBM预后的主要因素,积极的手术治疗和规范化、个体化的综合治疗可有效提高GBM病人的生存率.     

复发性多发胶质母细胞瘤的预后分析

目的 探讨复发性多发胶质母细胞瘤（GBM）预后的影响因素。方法 2005年1月至2012年12月手术切除并获得完整随访的复发性GBM 106例,其中单发78例,多发28例（多发组）;根据患者年龄、性别、肿瘤部位、手术切除程度、术后是否放化疗、术前KPS评分从单发GBM中选取与多发GBM相匹配的病例28例作为对照（单发组）;多发组根据肿瘤切除程度进一步分为全切组和部分切除组。结果 本组复发性多发GBM占26.4%。多发组中位生存期（4.5个月）明显短于单发组（8.5个月;P <0.05）。多发患者中,全切组中位生存期（7.9个月）明显长于部分切除组（3.7个月;P <0.05）。结论 复发性多发GBM预后较单发患者差;肿瘤切除程度越高,患者预后也越好,建议术中在保证重要功能的基础上尽量多切除肿瘤。     

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.     

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。     

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.     

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。     

儿童髓母细胞瘤患者临床因素与预后的相关性分析

目的 探讨影响儿童髓母细胞瘤(MB)患者预后的临床因素.方法 选择中山大学附属第一医院神经外科自2001年11月至2010年7月收治的儿童MB患者47例,采用Kaplan-Meier生存分析法和Cox回归模型分析患者年龄、性别、病程、肿瘤部位、术前转移、肿瘤切除程度、病理亚型、脑干侵袭程度、放疗与手术的时间间隔、化疗对生存时间即预后的影响.结果 本组患者2年生存率为91.4%,5年生存率为50%.Kaplan-Meier生存分析显示肿瘤全切或次全切者生存率高于大部分切除者,术前无转移患者生存率高于有转移者,放疗与手术的时间间隔≤42 d者生存率高于时间间隔>42 d者,差异均有统计学意义(P<0.05).Cox 回归模型分析显示术前转移、放疗与手术的时间间隔为儿童MB患者预后的影响因素,术前无转移、放疗与手术的时间间隔≤42 d患者预后较好.结论 术前有无转移和放疗与手术的时间间隔是影响儿童MB患者预后的独立因素.

Abstract：

Objective To analyze the correlation between the prognosis of pediatric medulloblastoma (MB) and its relevant clinical factors. Methods Forty-seven children with MB,admitted to our hospital from November 2001 to July 2010, were chosen;a retrospective analysis, using Kaplan-Meier survival tested by log-rank and Cox proportional hazards regression model, was performed to identify the correlation between the prognosis of pediatric MB and relevant clinical factors which included age, gender, course of disease, tumor location, pathological subtype, preoperative metastasis,extent of tumor resection, interval between surgery and radiation, brainstem invasion and chemotherapy.Results The 2-year survival rate of these patients was 91.4%, and 5-year survival rate 50%.Kaplan-Meier curves indicated that patients with total or subtotal tumor resection had a significantly higher survival rate than those with partial resection (P<0.05);patients without preoperative metastasis had a significantly higher survival rate than those with preoperative metastasis (P<0.05);and patients with interval between surgery and radiation≤42 d had a significantly higher survival rate than those with interval between surgery and radiation >42 d (P<0.05). Cox proportional hazards regression analysis indicated that preoperative metastasis (RR, 6.808;95%CI, 1.844 to 25.113;P<0.05) and interval between surgery and radiation (RR, 5.642;95% CI, 2.042 to 15.587;P<0.05) were the influencing factors for prognosis of MB. Patients without preoperative metastasis and with interval between surgery and radiation ≤42 d enjoyed good prognosis results. Conclusion Both preoperative metastasis and interval between surgery and radiation are independent factors for prognosis of pediatric MB.     

影响胶质母细胞瘤切除术后的预后因素分析

目的 探讨影响胶质母细胞瘤切除术后的预后因素.方法 对山东省三家医院1999-2004年经手术治疗且随访资料完整的205例胶质母细胞瘤进行回顾性研究,Kaplan-Meier单因素分析筛选预后相关因素,并通过Cox回归模型对筛选出的相关因素进行多因素分析.结果 患者中位生存期为12.0个月,术后6、12、18、24个月的积累生存率分别为82%、52%、27%、17%.多因素分析显示年龄、肿瘤部位、术前KPS评分、手术切除程度、术后放疗、化疗是影响预后的主要因素.结论 经多因素分析证实肿瘤的切除程度、术后放疗和化疗均能显著影响胶质母细胞瘤的预后,其中放疗是最具统计学意义的治疗方式.     

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。     

Medulloblastoma in pediatric age: a single-institution review of prognostic factors

We report a retrospective study of 35 cases of medulloblastoma in pediatric patients treated at our institution during an 18-year period. Ten of the patients were infants (age <2 years) and 25 were children (age >2 years). The main factors affecting prognosis were total removal of the tumor (P<0.01) and tumor stage (P<0.01). There were no differences between the survival rate of infants and children, infants had a worse prognosis in regard to quality of life than children.     

63例脑膜转移瘤预后因素分析

目的 探讨脑膜转移瘤(CM)的预后因素.方法 对天津医科大学附属肿瘤医院自1998年至2008年确诊的63例CM患者的临床资料进行回顾性分析,主要分析因素有性别、年龄、原发灶类别、KPS评分、确诊原发灶与发现脑膜转移瘤间隔时间、治疗方式、放疗剂量、原发灶控制情况等,Kaplan-Meier法计算生存期并绘制生存曲线,log-rank法进行检测验证,Cox多因素回归模型进行预后分析.结果 截止到随访结束,所有患者均已死亡,总生存期为2～732d,1年生存率为7.9%(5/63),中位生存期为67 d.Cox模型多因素分析显示KPS评分、原发灶控制情况、确诊原发灶与发现脑膜转移瘤间隔时间为独立预后因素.结论 CM主要预后因素为KPS评分、原发灶控制情况、确诊原发灶与发现脑膜转移瘤间隔时间.CM最佳治疗模式有待进一步研究,针对患者具体情况的个体化治疗值得在临床推广.     

53例儿童视路胶质瘤的临床特点及预后分析

目的 探讨我国儿童视路胶质瘤的临床特征、治疗方法及预后.方法 回顾性分析2003年4月至2011年1月在北京天坛医院小儿神经外科专业病房收治的53例视路胶质瘤患者临床资料,通过随访,分析无进展生存的影响因素.结果 本组患者平均年龄7.6岁(10个月～15岁),以DodgeⅡ型为主,均接受肿瘤部分切除术,随访到的41例患者中,其中30例稳定,11例进展,无进展生存期平均为26个月(3-64个月),术后是否接受放疗差异具有统计学意义(P＜0.01),合并神经纤维瘤病1型(NF-1)的2例,占4％.结论 我国儿童视路胶质瘤与国外报道的临床特征存在一定差别,肿瘤部分切除术可以有效降低手术并发症,结合术后放射治疗可有效控制肿瘤,获得较好的 治疗效果.     

基于放化疗敏感性相关基因的原发胶质母细胞瘤预后预测模型的构建和验证

目的筛选原发胶质母细胞瘤放化疗敏感性相关基因,基于相关基因构建原发胶质母细胞瘤患者的预后预测模型并验证。方法回顾性分析中国脑胶质瘤基因组图谱计划(CGGA)2019数据库(102例,试验组)和CGGA数据库(54例,验证组)中术后接受规范放化疗的原发胶质母细胞瘤患者的临床资料及转录组测序数据。在试验组中筛选长生存期亚组(≥18个月,49例)与短生存期亚组(≤9个月,22例)患者的差异基因,进一步将患者的年龄、肿瘤异柠檬酸脱氢酶(IDH)突变状态、染色体1p/19q共缺失状态、O6-甲基鸟嘌呤DNA甲基转移酶(MGMT)启动子区甲基化状态以及差异基因均纳入多因素Cox回归分析,筛选其中为独立预后因素的目标差异基因,取其风险比的自然对数作为各基因相应的系数,计算预后风险评分。采用单因素和多因素Cox回归分析法评估预后风险评分是否为独立预后因素;采用Kaplan-Meier法绘制生存曲线,log-rank检验比较高风险组(预后风险评分>0分)与低风险组(预后风险评分≤0分)患者生存期的差异。通过Pearson相关性分析筛选与风险评分呈正相关的基因,并对其进行功能富集分析。结果试验组中,长生存期亚组与短生存期亚组患者的性别、年龄、肿瘤切除程度、IDH突变状态、染色体1p/19q缺失状态以及MGMT启动子甲基化状态的差异均无统计学意义(均P>0.05)。长生存期亚组与短生存期亚组比较,9个基因表达量显著升高(均P<0.05),28个基因表达量显著降低(均P<0.05)。采用多因素Cox回归分析法筛选出4个目标差异基因,分别为AKR1C1(HR=0.910,95%CI:0.850~0.974,P=0.006)、CPZ(HR=0.947,95%CI:0.898~0.999,P=0.044)、HIST1H3H(HR=1.299,95%CI:1.025~1.647,P=0.031)以及TBX5(HR=1.104,95%CI:1.034~1.179,P=0.003),其对应的预测模型中的系数分别为-0.0947、-0.0547、0.2624、0.0994。试验组和验证组中,预后风险评分(高风险)均为预后的独立危险因素(试验组中,HR=2.407,95%CI:1.470~3.939,P<0.001;验证组中,HR=2.054,95%CI:1.101~3.830,P=0.024)。试验组和验证组中,高风险亚组(分别为51、22例)患者的总生存期均比低风险亚组(分别为51例、32例)短,差异均有统计学意义(均P<0.05)。功能富集分析结果显示,在试验组与验证组中,与预后风险评分正相关的基因更多地富集在细胞增殖、基因表观遗传学调控、DNA修复及核因子κB信号通路的激活等生物学功能上。结论基于放化疗敏感性相关基因AKR1C1、CPZ、HIST1H3H以及TBX5构建的预后预测模型或可用于预测原发胶质母细胞瘤患者的预后。     

Use of adjuvant ICE chemotherapy in the treatment of anaplastic ependymomas

Despite the improved outcome for patients with ependymoma treated by surgery and radiotherapy, their prognosis remains relatively poor. To assess the impact of adjuvant chemotherapy, we reviewed the overall survival of consecutive patients with anaplastic ependymoma treated over a 10-year period with surgery and ICE (ifosfamide+ VP16+carboplatin) chemotherapy with or without radiation at our institution. There were 11 patients (6 male, 5 female), with a median age of 3.4 years (range 1.2–11.1): 4 under 2 years and 7 were over 2 years old. Overall, 5 had gross total resections: 4 are alive, 2 in continuous complete remission and 2 in second complete remission. One patient who was less than 2 years old died. Among the 6 with subtotal resection, 2 achieved a complete remission after chemotherapy. However, 5 of the 6 patients have since died of progressive disease, with a median overall survival of 75 months. Overall survival was 24% and progression-free survival was 39%. In 2 of 6 patients with residual postoperative disease a temporary objective response was noted with adjuvant ICE chemotherapy. This regimen did not confer an overall survival advantage. Received: 24 July 1998     

Glioblastoma: clinical characteristics, prognostic factors and survival in 492 patients

Objective

Glioblastoma is the most common and most malignant primary brain tumor in adults. The only overall accepted independent prognostic factors are patient age and performance. We present a large single institution patient series examined for prognostic factors using uni- and multivariate survival analysis.

Methods

492 patients were included who underwent craniotomy for newly diagnosed glioblastoma WHO grade IV between 1990 and 2007 at our department. The association to patient survival was estimated using log-rank test for univariate analysis and cox regression method for multivariate analysis.

Results

Median patient age was 62 years (mean: 60.4 years, range: 22–93 years), the male: female ratio was 1.26:1. Primary genesis was found in 91.0% of cases. A multifocal tumor was present in 110 cases (22.4%). The median pre- and post-operative Karnofsky Performance Score was 70. Total tumor resection was performed in 288 cases (58.5%), subtotal removal in 134 cases (27.2%). The following parameters were significantly associated with survival in univariate analysis: age, performance, primary genesis, multifocal tumor, neurological deficit, neuropsychological findings, seizures, incidental finding, total or subtotal resection, radiotherapy, chemotherapy, combined radio-/chemotherapy with temozolomide, re-craniotomy, second tumor in patient history. The following parameters were significantly associated with survival in multivariate analysis: age, performance, multifocal tumor, total or subtotal resection, radiotherapy, chemotherapy, combined radio-/chemotherapy with temozolomide.

Conclusion

In addition to patient age and performance, we identified multiple lesions and resection status as independent prognostic factors. Radiotherapy, chemotherapy and combined radio-/chemotherapy with temozolomide were significantly associated with prolonged survival.     

Efficacy of temozolomide as adjuvant chemotherapy after postsurgical radiotherapy alone for glioblastomas

Objectives

The aim of this study was to assess the efficacy of adjuvant TMZ chemotherapy for newly diagnosed GBM patients who were treated with surgery followed by radiotherapy alone.

Material and methods

Between January 2003 and April 2005, 59 consecutive GBM patients underwent radiation therapy after surgical resection and subsequently received TMZ chemotherapy. For the comparative analysis, we selected 60 clinically matched GBM patients who underwent radiotherapy followed by nitrosourea-based chemotherapy (NUBC), at the same institution between June 1995 and April 2005. The study cohort was divided into two groups, those with adjuvant TMZ treatment and with NUBC.

Results

59 patients with adjuvant TMZ treatment were assigned to the treatment group and 60 patients with NUBC to the control group. The median overall survival for the treatment group was 18.2 months (95% CI, 11.7–24.7 months), compared with the survival of 14.5 months (95% CI, 11.2–17.7 months) for the control group (p = 0.019). The progression-free survival for the treatment group was 5.6 months (95% CI, 4.4–6.7 months), while the control group showed progression-free survival of 3.3 months (95% CT, 3.2–6.0 months) (p = 0.030). Uni- and multivariate analysis revealed that extent of surgical resection, age ≥55 years and postoperative KPS were significantly associated with survival.

Conclusion

Adjuvant TMZ chemotherapy provided a clinically relevant benefit of survival, as compared with NUBC. Thus, we suggest that adjuvant TMZ chemotherapy may be effective even for patients who did not receive concomitant chemoradiotherapy for GBM.