顺铂联合替莫唑胺治疗MGMT启动子非甲基化的 复发高级别胶质瘤

目的 探讨顺铂（DDP）联合替莫唑胺（TMZ）治疗MGMT启动子非甲基化的复发高级别胶 质瘤的疗效。方法 纳入2016 年4 月30 日至2018 年3 月31 日收治55 例MGMT启动子非甲基化的复发 高级别胶质瘤,均经过手术病理证实为高级别胶质瘤（WHO Ⅲ级或Ⅳ级）和MGMT启动子非甲基化。随 访期间经头颅MRI 和（或）再次手术的病理确诊为肿瘤复发,并给予DDP联合TMZ化疗。观察患者的不 良反应和生存情况。结果 WHO Ⅲ级有效率为12.0%（3/25）,中位生存期为42 个月;WHO Ⅳ级有效率 为6.7%（2/30）,中位生存期为17 个月。总有效率为9.1%（5/55）,总生存期为19 个月。不良反应主要为骨 髓抑制、胃肠道症状和肝肾功能损伤,经对症治疗后均恢复。结论 DDP 联合TMZ 治疗MGMT 启动子 非甲基化的复发高级别胶质瘤具有一定的疗效。     

成人高级别脑胶质瘤术后替莫唑胺联合依托泊苷治疗的临床运用与观察

目的比较替莫唑胺联合依托泊苷与单用替莫唑胺在成人高级别脑胶质瘤术后综合治疗中的疗效差异。方法 42例成人高级别脑胶质瘤患者行手术切除病灶,术后随机分为两组,单药组(单用替莫唑胺)和联合治疗组(替莫唑胺联合依托泊苷)。比较两组患者的无进展生存期及不良反应。结果单药组和联合治疗组的中位无进展生存时间分别为17.5周和24.4周,6个月无进展生存率分别为31.8%和45.0%。联合治疗组的无进展生存期和6个月无进展生存率均要明显高于单药组(均P0.05)。同时,两组患者的不良反应无显著差异。结论在成人高级别脑胶质瘤术后综合治疗中,替莫唑胺联合依托泊苷的化疗疗效要优于单用替莫唑胺治疗,该方案值得临床推广。     

贝伐单抗联合化疗治疗复发高级别胶质瘤的疗效观察及安全性分析

目的探讨贝伐单抗联合化疗治疗复发高级别胶质瘤的疗效及安全性。方法回顾性分析2011年3月~2013年12月符合入选标准的11例复发高级别胶质瘤患者,接受贝伐单抗联合替莫唑胺(TMZ)化疗方案治疗。化疗效果按照肿瘤可计算MRI增强范围评价疗效,并观察患者治疗前至再次进展之间KPS、QOL评分改变。不良反应参照WHO抗癌药物急性与亚急性毒性反应分度标准。结果 11例患者全部完成2个周期以上的化疗。疗效评价,总体完全缓解(CR)4例,部分缓解(PR)6例,病情稳定(SD)1例,病情进展(PD)0例,缓解率(RR)为90.9%(10/11),DCR为100%(11/11);中位PFS为5.4个月,中位OS为6.5个月。贝伐单抗联合TMZ所致不良反应以胃肠道反应(66.3%)、骨髓抑制(43.2%)、肾损伤(39.0%)、高血压(27.3%)常见,本组多为Ⅰ、Ⅱ级(35.93%),很少Ⅲ级(2.60%),无Ⅳ级;治疗后患者KPS评分及QOL评分均较治疗前均有改善(均P0.05)。结论贝伐单抗联合TMZ化疗对复发高级别胶质瘤的治疗有良好的抗肿瘤活性和较高的疾病控制率,安全性较高,是一种可优先选择的治疗方法。     

复发高级别胶质瘤的治疗

尽管给以联合的治疗方案,高级别胶质瘤最终都会迅速复发。复发后的病人一般状态不同,分子生物学特点各异,为了获得最长的高质量生存期,治疗方案的选择非常重要。本文拟从复发高级别胶质瘤的诊断、不同体能状态和各种不同治疗方案对病人的影响等几个方面进行综述,以期寻找复发高级别胶质瘤的最适合治疗方法。     

放、化疗同步治疗高级别胶质瘤

目的比较单纯放疗与放疗加替莫唑胺（放疗同时和放疗后给药）治疗高级别胶质瘤的局控率、生存率及不良反应。方法对52例首次术后的问变性星形及胶质母细胞瘤随机分为接受单纯放疗（分次照射局部放疗，2Gy／d，5d／w，共持续6W，总剂量60Gy）、放疗加每天持续的替莫唑胺治疗（75mg／m^2／d），7d／w，从放疗开始到放疗结束）以及6个周期的替莫唑胺辅助治疗（150～200mg／m^2，治疗5d，每28d为一个疗程）。每组26例。主要研究目标为整体生存率。结果放疗加替莫唑胺（RT—TMZ）组与单纯放疗（RT）组总有效率（CR＋PR）分别为76．9％和50．0％；6个月无进展生存率分别为73．1％和46．2％；中位无进展生存期分别为8．8个月和6．2个月（P〈0．05）。1年累积局部复发率分别为42．3％和76．9％；1年无复发生存率分别为57．7％和23．1％，1年生存率分别为65．4％和30．8％（P〈0．05）。RT—TMZ组常见不良反应是恶心，呕吐，白细胞和血小板下降，但仅限于Ⅰ～Ⅱ度。结论两组相比在提高局控率、延缓肿瘤复发与提高患者无瘤生存期方面RT—TMZ组要优于RT组，而不良反应方面两组反应均较轻微，所以放疗加替莫唑胺治疗新确诊的间变性星形及胶质母细胞瘤有效并能够明显提高生存率而毒副作用小。     

颈内动脉超选择灌注卡铂治疗颅内胶质瘤和转移瘤临…

本文报告经颈内动脉超选择灌注卡铂治疗胶质瘤１０例，颅内转移癌２例。化疗前及化疗后一月检查ＣＴ比较瘤体变化。１０例胶质瘤中８例瘤体缩小１０％～２０％，２例瘤体增大。２例转移癌中１例瘤体完全消失，１例瘤体缩小７０％。全部患者均无视网膜及神经系统毒性反应。根据国际通用的肿瘤疗效观察标准分析，颈内动脉超选择灌注卡铂治疗胶质瘤效果不理想，但对颅内转移癌有满意的疗效。本文对颈内动脉灌注给药的方式方法进行了探讨     

老年高级别胶质瘤的临床特点和治疗

目的探讨老年高级别胶质瘤患者的临床特点和治疗方案。方法回顾性分析2012年4月至2017年8月中国医学科学院,北京协和医院神经外科连续收治的32例老年高级别胶质瘤患者的临床资料,总结其临床表现、术前Karnofsky功能状态评分(KPS)、合并症情况(查尔森合并症指数)、肿瘤病理学分型、治疗方法以及患者的总生存期。所有患者均行手术切除肿瘤或活组织检查术,术后辅以放化疗、单纯化疗或靶向治疗。采用Kaplan-Meier法探讨手术方式、合并症情况以及术前KPS对患者总生存期的影响。结果32例患者中,男21例,女11例;年龄为(71.9±6.9)岁(65~79岁);其中世界卫生组织(WHO)Ⅳ级(胶母细胞瘤)22例(68.7%),Ⅲ级10例(31.3%);术前中位KPS(范围)为78.1分(40~90分);中位查尔森合并症指数(范围)为5.7(4~8)。32例患者中,行病灶切除术21例(65.6%),行活组织检查术11例(34.4%)。术后行标准Stupp方案治疗7例,行替莫唑胺辅助化疗9例,行靶向治疗1例,未行进一步治疗11例。失访4例。32例患者的总生存期为1.2~73.3个月,中位值为15.8个月。生存分析结果表明,手术方式、术前KPS以及查尔森合并症指数并非患者总生存期的影响因素(均P>0.05)。结论老年高级别胶质瘤患者的一般情况较差,合并症多,通过采用手术、放化疗等综合治疗后生存期仍较短。在进行治疗方案的选择时,应根据患者的具体情况选择相对有利的治疗方案。     

脑胶质瘤临床复发的原因分析

1 对象与方法1.1 一般资料40例首次手术肉眼全切并电凝瘤周正常组织的脑胶质瘤病人,其中男25例,女15例;年龄16~65岁,平均39.6岁。术后复发时间为5~34个月,平均11个月。肿瘤部位:额叶13例,颞叶4例,枕叶5例,顶枕6例,额颞8例,颞顶4例。星形细胞瘤Ⅰ级3例,Ⅰ~Ⅱ级5例,Ⅱ级3例,Ⅱ~Ⅲ级6例,Ⅲ级12例,Ⅲ~Ⅳ级6例,Ⅳ级5例。1.2 CT检查首次手术前后及复发时均行头颅CT平扫及增强扫描。首次CT示瘤周围水肿32例。术后首次CT扫描均未见肿瘤残留,22例原瘤周围有水肿带。复发后CT示复发肿瘤位于原水肿区者17例。2 结果第2次手术见复发肿瘤…     

高级别胶质瘤的治疗现状及思考

正高级别胶质瘤包括间变型胶质瘤(WHOⅢ级)和胶质母细胞瘤(WHOⅣ级)。胶质瘤的治疗方案包括手术、放疗以及化疗。针对胶质母细胞瘤,Stupp方案是目前国际通行的标准治疗方案——在最大程度保护脑功能前提下最大范围手术切除肿瘤,随后同步替莫唑胺(temozolomide,TMZ)的放疗,以及后续的TMZ化疗[1];其中位生存期为14.6个月[1]。自Stupp方案报道以来,已近10年,虽然高级别     

卡铂与鬼臼乙叉甙联合应用治疗复发性恶性幕上脑胶质瘤

目的 探讨卡铂与鬼臼乙叉甙联合治疗复发性恶性幕上脑胶质瘤的疗效。方法 对３１例复发性恶性幕上脑胶质瘤患者给予卡铂与鬼臼乙叉甙各１００ｍｇ／ｍ＾２,每日１次,静脉滴注连续３天,疗程每４周重复１次,至少用３个疗程,每个程程后分别进行评价。结果３１例中部分缓解４例,稳定１０例,部分缓解和率共计为４５％,部分缓解和稳定患者的中位恶化期为２８周,中位生存期为５１周。全组患者中位生存期为４５周。结论 卡我后     

Preirradiation ifosfamide,carboplatin, and etoposide (ICE) for the treatment of high-grade astrocytomas in children

Background Astrocytomas are the most common form of primary intracranial tumor; however, survival of patients with high-grade tumors has not changed much compared with that reported in the early 1970s.Objective Our objective was to assess the efficacy, security, and survival rate of postoperative chemotherapy with ifosfamide, carboplatin, and etoposide (ICE) in pediatric patients with anaplastic astrocytomas (AA) and glioblastoma multiforme (GM).Methods In a phase II study, we evaluated 25 children with AA or GM. The proposed treatment was four courses of chemotherapy with ICE followed by hyperfractionated radiotherapy, and then four more courses of ICE. Patients were evaluated using MRI after surgery, after the second course of chemotherapy, and again after the last. Toxicity was determined before each course.Results The overall and disease-free survival at 60 months was 67% and 56% respectively. For supratentorial localization it was 92% at 60 months and 20% at 18 months for brain stem tumors. Fourteen patients had a complete response and 9 died as a result of tumor progression.Conclusions Postoperative chemotherapy with ICE reduces the tumor size and increases the survival rate of pediatric patients with malignant astrocytomas with minimal toxicity.A commentary on this paper is available at     

Carboplatin and etoposide combined with bevacizumab for the treatment of recurrent glioblastoma multiforme

Relapsed glioblastoma multiforme (GBM) responds poorly to standard therapies. Vascular endothelial growth factor (VEGF) is implicated in the development of GBM and the anti-VEGF monoclonal antibody bevacizumab has shown early clinical promise against malignant glioma. We treated six patients with recurrent GBM using bevacizumab combined with carboplatin and etoposide chemotherapy (ACE regimen). Toxicity was that expected for carboplatin and etoposide alone, except for an ischemic stroke in one patient. We observed partial responses in five patients and one responding patient developed extensive tumour necrosis after 2 cycles of treatment. Median progression-free and overall survival was 19 and 29.9 weeks, respectively. Four responding patients developed recurrence, which was characterized by markedly less peri-tumoral edema, mass effect and necrosis compared with tumours at baseline. Two patients developed local extracranial extension. In conclusion, ACE was active in recurrent GBM and was mostly well tolerated.     

长春西汀对抑郁症的辅助治疗作用

目的：探讨文拉法辛联合长春西汀对复发性抑郁症的疗效和不良反应。方法：复发性抑郁症患者78例,按就诊及确诊顺序编号,单号为合用组（文拉法辛联合长春西汀）;双号为单用组（单用文拉法辛）。疗程4周。采用汉密尔顿抑郁量表（HAMD）和治疗中出现的症状量表（TESS）评定疗效和不良反应。结果：两组HAMD评分均较治疗前显著下降（P〈0.01）;治疗4周,以合用组HAMD评分显著低于单用组（P〈0.01或P〈0.05）。两组不良反应差异无显著性（P〉0.05）。结论：文拉法辛联合长春西汀治疗抑郁症的效果优于单用文拉法辛,长春西汀对复发性抑郁症有辅助治疗作用。     

Usefulness of circulating tumor DNA from cerebrospinal fluid in recurrent high-grade glioma

Molecular documentation at relapse of high-grade glioma is an urgent need for patient care. A prospective pilot study was conducted to assess the rate of mutation detection using targeted deep sequencing on circulating tumor DNA from cerebrospinal fluid (CSF) after chemo-radiotherapy based treatment. Fifteen patients were included: 13 patients with glioblastoma, 1 patient with gliosarcoma and 1 patient with anaplastic astrocytoma. At progression, 10/15 patients (67%) had detectable mutations in the CSF. Among them, 5/10 patients harbored at least one common mutation between initial tumor and ctDNA. CSF protein level and cfDNA concentration were higher, although not significant, in the ctDNA positive group versus ctDNA negative group (1.17 g/L vs. 0.79 g/L). Molecular documentation obtained from ctDNA in CSF at the time of relapse is informative in around two-thirds of the patients.     

Carboplatin combined with carmustine and etoposide in the treatment of glioblastoma

The aim of this study was to verify the tolerability and efficacy of therapeutic chemotherapy protocols, employing different combinations of cis-platin, carbo-platin, etoposide and carmustine in primary glioblastoma patients. The purpose was focused on 2 end points: the response index to treatment, the TTP (tumor progression) and the ST (survival time). Eighty-four out of a group of 99 consecutive glioblastoma patients, entered this study. Patients were divided into 4 disparate treatment groups: (A) BCNU alone; (B) CDDP+VP-16; (C) CBDCA+BCNU; (D) CBDCA+BCNU+VP-16. The effectiveness and the TTP of the protocols differed, but differences were not statistically significant. Data concerning platinum treatment compare favorably with the best literature results. At 18 months more than half the carboplatin-treated patients are alive. Moreover these patients had a significantly longer ST than those treated with BCNU. We conclude that platinum-based chemotherapy has a beneficial effect on glial tumors.Paper presented at the National Congress at Sorrento in 1991 and selected by the Editorial Board of the Journal     

复发性脑胶质瘤的临床治疗进展

脑胶质瘤是最常见的中枢神经系统恶性肿瘤,大多数脑胶质瘤患者在接受标准疗法治疗后都会复发。目前尚没有复发性脑胶质瘤治疗的标准及共识,该文就复发性脑胶质瘤的临床治疗进展进行综述。     

Safety and feasibility of long-term temozolomide treatment in patients with high-grade glioma

We surveyed neuro-oncologists regarding patients treated with temozolomide for at least 12 cycles or 12 months. Patients receiving first-line temozolomide for a median 13 cycles had a median progression-free survival (PFS) of 14 months. Patients with recurrent disease receiving a median 14 cycles had a median PFS of 15.5 months. A small percentage of patients experienced grade III to IV toxicity. These results suggest that long-term treatment with temozolomide is feasible and well tolerated.     

BCNU as second line therapy for recurrent high-grade glioma previously treated with Temozolomide.

BCNU has an established role in the treatment of high-grade gliomas and has previously been used as first line therapy for recurrent disease. More recently, Temozolomide has taken its place as first line therapy for recurrent high-grade glioma. Thus, BCNU has become our standard second line therapy following disease progression after Temozolomide therapy. This study retrospectively analysed the activity and toxicity associated with BCNU as second line therapy. Twenty four patients with recurrent high-grade gliomas were treated with BCNU having previously received Temozolomide. Patients received BCNU intravenously at 130-200 mg/m2 every 6 weeks. The median number of treatment cycles was two (range 1-8). Of the 24 patients, one patient (4%) achieved a partial response and six (25%) achieved a minor response or stable disease. BCNU was generally well tolerated. In conclusion, BCNU has limited activity as second line chemotherapy following the use of Temozolomide. Novel strategies are required in this patient group.