放化疗同步与单纯放疗治疗胶质母细胞瘤的疗效比较

目的 比较单纯放疗(RT)与放疗加替莫唑胺(RT-TMZ)治疗胶质母细胞瘤的局控率、生存率及不良反应.方法 对60例首次术后的胶质母细胞瘤随机分为接受单纯放疗、放疗加每天持续的替莫唑胺治疗以及6个周期的替莫唑胺辅助治疗.每组30例.主要研究目标为整体生存率.结果 RT-TMZ组与RT组总有效率分别为53.3%和26.6%;1年累计局部复发率分别为63.3%和90.0%,1年无复发生存率分别为36.7%和10.0%,1年生存率分别为56.7%和16.7%(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 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.     

原发性脑胶质瘤术后替莫唑胺化疗的临床观察

目的观察应用替莫唑胺（TMZ）治疗手术后脑原发性胶质瘤患者的疗效和安全性。方法选择26例年龄为18～60岁，经病理检查诊断为星形细胞瘤（Ⅱ～Ⅳ级）患者，其中间变性星形细胞瘤（Ⅱ～Ⅲ级）18例，胶质母细胞瘤（Ⅳ级）8例。给予TMZ150-200mg／（mz·d），连续空腹口服5d，28d为一个疗程（本组患者治疗3-6个疗程）。每一个疗程均随访患者的临床表现，血常规及肝、肾功能，以判断患者能否耐受。TMZ治疗第三及第六个疗程末施行相应的增强CT或MRI检查，与化疗前的影像学资料进行比较，判断肿瘤实体变化情况。结果26例患者中有3例肿瘤完全消失，2例肿瘤体积缩小〉50％，5例病情稳定，5例无反应，11例肿瘤体积增大，治疗有效率为10／26，患者6个月生存率为16／26。生存最长者已达20个月。化疗期间患者的不良反应及骨髓毒性较轻微。结论TMZ能有效地延缓肿瘤复发．且安全性和耐受性较好，为一有良好前景的化疗药物。     

三维适形放疗联合替莫唑胺化疗对术后脑胶质瘤的疗效观察

目的分析比较三维适形放疗联合替莫唑胺化疗和单纯放疗对脑胶质瘤部分切除术后患者的疗效和安全性。方法选取自2003年10月至2006年6月42例脑胶质瘤部分切除术后患者，随机分为2组：单纯放疗组（19例）仅行三维适形放疗，分次局部照射，2．0Gy／次，1次／d，5d／周，共持续6周，总剂量60Gy；联合治疗组（23例）于三维适形放疗同时联合替莫唑胺化疗6周＋辅助化疗6疗程。影像学动态观察患者肿瘤体积的变化及Karnofsky评分评价神经功能状态。结果放疗结束24周后，联合治疗组在影像学所示肿瘤实体的缩小和神经功能状态（日常生活能力）的改善方面均优于单纯放疗组（P〈0．05）。结论放疗联合替莫唑胺化疗可提高脑胶质瘤部分切除术后肿瘤缓解率和患者生活质量。     

替莫唑胺胶囊治疗恶性脑胶质瘤30例疗效分析

目的评价替莫唑胺胶囊（TMZ）治疗人脑恶性胶质瘤的临床疗效及不良反应。方法2005年1月至2008年1月对一个单位30例术后确诊的恶性脑胶质瘤且使用TMZ化疗的患者进行随访,观察近期治疗反应、生存期,并分析常规病理和分子病理对治疗效果的影响。结果TMZ治疗结束时,30例患者客观有效率和疾病控制率分别为53．3％和80．0％,O^6-甲基鸟嘌呤-DNA甲基转移酶（MGMT）对近期疗效无明显影响（P〉0．05）,而不同病理类型的近期疗效存在明显差异（P〈0．05）。随访期间共有12例患者死亡,生存期为0．7～3．7年,中位生存期为1．5年。MGMT阳性和阴性患者的中位生存期分别为1．3年和1．5年,无明显差异（P：0．31）。胶质母细胞瘤和间变型星形细胞瘤的中位生存期分别为1．3年和2．0年,亦无明显差异（P=0．28）。不良反应包括厌食、便秘等消化道症状11例（36．7％）,白细胞减少3例（10．0％）,假性进展2例（6．7％）。结论TMZ对恶性胶质瘤患者有较好的临床疗效,不良反应少,耐受性好,治疗方案简便,是一种理想的恶性胶质瘤术后辅助化疗药物。     

替莫唑胺联合调强放疗治疗胶质母细胞瘤术后残留临床研究

目的分析比较替莫唑胺化疗联合调强放疗和单纯调强放疗治疗脑胶质母细胞瘤术后残留患者的疗效和安全性。方法胶质母细胞瘤术后局部有残留患者共36例,随机分为观察组和对照组,各18例。观察组在调强放疗时同步口服替莫唑胺化疗,对照组行单纯调强放疗,两组放疗方法相同。治疗期间观察治疗副作用,在所有患者治疗结束后定期随访,影像学动态观察患者肿瘤体积的变化及Karnofsky评分评价神经功能状态。结果观察组肿瘤体积的缩小和神经功能评分的改善均优于对照组(P0.05)。两组生存率比较有统计学意义(P0.05)。两组不良反应有恶心、呕吐、头痛及骨髓抑制等,程度均较轻,无重要脏器损害,未影响治疗。结论替莫唑胺化疗联合调强放疗疗效优于单纯调强放疗,且不良反应可耐受。     

精确放疗同步替莫唑胺治疗胶质母细胞瘤疗效初探

目的 探讨精确放疗同步替莫唑胺化疗对多形性胶质母细胞瘤的临床疗效.方法 回顾性分析2009年7月至2010年12月北京世纪坛医院收治的54例多形性胶质母细胞瘤,术后接受精确放疗(三维适形或调强放疗)同步替莫唑胺化疗,随后接受替莫唑胺辅助化疗.结果 全组共21例死亡,均死于肿瘤复发.全组1年总生存率为79.6％,1年无进展生存率为48.7％.32例出现复发,其中原位复发为16例.卡氏评分(KPS≥70分)组1年总生存率显著高于卡氏评分(KPS＜ 70分)组(86.8％与50.8％,P=0.005).全切或近全切除组1年总生存率高于部分切除组(84.4％与70.5％,P=0.067).仅2例出现3度以上不良反应(骨髓抑制).结论 精确放疗同步替莫唑胺化疗是多形性胶质母细胞瘤安全有效的治疗模式,卡氏评分和手术切除肿瘤的程度是影响生存的重要因素.     

高分级脑胶质瘤术后三维适形放疗联合替莫唑胺化疗的疗效

目的回顾性分析高分级脑胶质瘤术后三维适形放疗联合替莫唑胺化疗的临床疗效及安全性。方法收集2008-05—2011-05在我院治疗的高分级脑胶质瘤术后患者38例,其中间变性星形细胞瘤(WHO 3级)26例,多形性胶质母细胞瘤(WHO 4级)12例,手术完整切除22例,残留16例。均用三维适形放疗(3DCRT),5d/周,1次/d,2Gy/次,总量52~66Gy/[(26~33)次·(5.5~6.5)周],其中≥60Gy者28例,<60Gy者10例。替莫唑胺150mg/(m2·d),顿服,连续5d,28d为1周期,放疗第一周开始口服,共4个周期。结果全组1、3a生存率分别为68.4%、31.6%,中位生存时间为(21.23±4.45)个月;手术完整切除与手术残留组1、3a生存率分别为77.3%、45.5%与56.3%、12.5%(P<0.05);放疗剂量≥60Gy组与<60Gy组1、3a生存率分别为78.6%、39.3%与40.0%、10.0%(P<0.05)。急性放化疗反应主要为皮肤反应、白细胞减少、胃肠道反应及急性脑损伤反应。晚期发生放射性脑损伤仅2例。结论术后三维适形放疗联合替莫唑胺治疗高分级脑胶质瘤有较好的临床疗效,不良反应小,但手术后残留患者预后差,推荐术后放疗剂量不低于60Gy。     

恶性胶质瘤替莫唑胺治疗有效

美国临床肿瘤学会（ASCO）发表2005年临床肿瘤研究进展报告．评出肿瘤临床研究十一项重大进展，其中包括恶性胶质瘤替莫唑胺治疗有效。两项研究表明：替莫唑胺加放疗可延长某些恶性胶质瘤病人的寿命。恶性胶质瘤是一种高度耐药的脑肿瘤。替莫唑胺可抑制癌细胞的增殖和播散。替莫唑胺加放疗组的生存期比单纯放疗组长（14．6个月对12．1个月。替莫唑胺加放疗组2年生存率是放疗组的2倍以上。另一项研究表明：替莫唑胺治疗有效病人的肿瘤细胞往往具有特定遗传标志（MGMT基因改变）。     

恶性脑胶质瘤术后替莫唑胺同步放化疗的疗效观察

目的探讨恶性脑胶质瘤术后替莫唑胺同步放化疗的疗效。方法选取2009-02—2010-08于我院就诊并住院的脑胶质瘤术后患者98例,分为单纯放疗组和同步放化疗组各49例,单纯放疗组接受单纯放疗(DT 60Gy),同步放化疗组在此基础上加服替莫唑胺75mg/(m2·d)同步化学治疗,放疗后口服替莫唑胺150~200mg/(m2·d),连续服用5d,每个疗程28d,服用6个疗程。2组治疗过程中均给予甘露醇和地塞米松等药物以降低颅内压。比较2组1、3、5a生存率。结果单纯放疗组1、3、5a生存率分别为61.22%、24.49%、14.29%,同步放化疗组分别为79.59%、51.02%、32.65%,同步放疗组疗效优于单纯放疗组(P0.05)。结论替莫唑胺同步放化疗在恶性脑胶质瘤术后的疗效优于术后单纯放疗。     

肿瘤治疗电场联合替莫唑胺化疗与单独使用替莫唑胺化疗对胶质母细胞瘤临床疗效比较的Meta分析

目的 探讨单独使用替莫唑胺（TMZ）与替莫唑胺联合肿瘤治疗电场（TTF）治疗胶质母细胞瘤安全性和疗效的比较。方法 检索Pubmed、Cochrance、Embase、Ovid、Scopus、Web of Science、中国知网、万方数据知识服务平台、维普中文期刊数据库、中国生物医学文献服务系统数据库、谷歌学术自建库至2020年4月5日的文献,筛选TMZ和TTF+TMZ进行疗效比较的随机对照研究,按照纳入和排除标准,把总体生存率（OS）和无进展生存期（PFS）作为结局指标,最后使用Review Manager进行统计分析。结果 最终纳入4篇研究,共1091例患者,其中单纯TMZ组381例,TTF+TMZ组710例。TTF+TMZ组的平均OS （26.9个月）和平均PFS （14.7个月）,优于单纯TMZ组的平均OS （12.63个月）和平均PFS （5个月）（P<0.01）。结论 TTF+TMZ治疗GBM的有效性优于单纯使用TMZ的患者。     

Adjuvant chemotherapy for adults with malignant glioma: a systematic review

OBJECTIVE: This systematic review examines the role of chemotherapy following surgery and external beam radiotherapy for adults with newly diagnosed malignant glioma. METHODS: MEDLINE, EMBASE, and the Cochrane Library databases were searched to August 2006 to identify relevant randomized controlled trials (RCTs) and meta-analyses. Proceedings from the 1997 to 2006 annual meetings of the American Society of Clinical Oncology were also searched. RESULTS: Two RCTs reported a survival advantage in favour of radiotherapy with concomitant and adjuvant temozolomide compared with radiotherapy alone in patients with anaplastic astrocytoma or glioblastoma. Twenty-six RCTs and two meta-analyses detected either no advantage or a small survival advantage in favour of adjuvant chemotherapy. CONCLUSION: Concomitant temozolomide during radiotherapy and post-radiation adjuvant temozolomide is recommended for all patients ages 18-70 with newly diagnosed glioblastoma multiforme who are fit for radical therapy (ECOG 0-1). Temozolomide may be considered in other situations (i.e., ECOG 2, biopsy only, age > 70, intermediate grade glioma), but there is no high-level evidence to support this decision. Moreover, there are few data on long-term toxicities or quality of life with temozolomide. Adjuvant chemotherapy may be an option for younger patients with anaplastic (grade 3) astrocytoma and patients with pure or mixed oligodendroglioma. However, there is no evidence of a survival advantage from adjuvant chemotherapy in these patients, and treatment-related adverse effects and their impact upon quality of life are poorly studied. The combination of procarbazine, lomustine, and vincristine (PCV) is not recommended for patients with anaplastic oligodendroglioma and oligoastrocytoma.     

Clinical outcome of concomitant chemoradiotherapy followed by adjuvant temozolomide therapy for glioblastaomas: Single-center experience

Introduction

The use of radiotherapy plus temozolomide administered concomitantly with and after radiotherapy for glioblastoma was recently shown to improve median and 2-year survival in a large international multicenter study. To compare this result in routine clinical practice, an audit of the management and outcome of patients with glioblastoma at our institute was performed.

Methods

A total of 79 patients with pathologically confirmed glioblastoma were treated with radiotherapy (daily fractions of 2 Gy for a total of 60 Gy) combined with temozolomide at a dose of 75 mg/m² per day, followed by 6 cycles of adjuvant temozolomide (150–200 mg/m², 5 consecutive days per month). The primary end point was overall survival (OS). Secondary endpoints included progression-free survival (PFS) and toxicity. We evaluated the clinical outcome of concomitant chemoradiotherapy for newly diagnosed glioblastomas at a single institute in Korea.

Results

The median age was 52 years (15–76 years), 47 patients were male and 32 patients were female. 92.4% of the patients had undergone debulking surgery. The median overall survival (OS) was 18.3 months (95% CI, 16.3–20.1 months), and the time to progression was 6.7 months (95% CI, 5.2–8.3 months). The 1-year and 2-year survival rates were 70.1% and 37.1%, respectively. In the retrospective analysis, the patients with a post-operative KPS over 80 showed more prolonged survival than those who had a KPS less 80 (23.1 months vs. 13.4 months; p < 0.001). Age and extent of surgery did not emerge as significant factors. Twenty-four patients (30%) were treated with low-dose continuous temozolomide therapy after the tumor had recurred. Hematologic toxicity was the main adverse effect, occurring in seven patients (8.8%). Patients with lymphopenia were not reported.

Conclusions

This study is the largest study of radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma in Korean patients, who share a common genetic feature. The median and 2-year survival outcomes in this study are comparable to the previous reports. However, for the recurrent glioblastomas refractory to temozolomide, further clinical trials using other agents should be studied continuously in the future.     

Loco-regional treatments in first-diagnosis glioblastoma: literature review on association between Stupp protocol and Gliadel

Loco-regional chemotherapy with carmustine wafers (Gliadel) positioned at surgery and followed by radiotherapy has been shown to prolong survival in first-diagnosis glioblastoma, as well as concomitant radiochemotherapy with temozolomide. The combination of Gliadel with the Stupp protocol has mostly been investigated in retrospective studies. objective of this study was to review the literature of efficacy and toxicities in patients with first-diagnosis glioblastoma treated with surgery, Gliadel, radiotherapy and temozolomide chemotherapy. The data in the literature regarding the combined use of Gliadel with chemotherapy, concomitant with radiotherapy and adjuvant temozolomide for glioblastoma was analyzed and compared. The results on survival and toxicity are summarized. The combination of Gliadel and radiotherapy with temozolomide is well tolerated and may increase survival without a substantial increase in major toxicity. However, only prospective comparative studies will be able to address the issue of true advantage in survival with this combination.     

Effects of treatment on long-term survivors with malignant astrocytomas

We reviewed the records of 160 consecutive patients with glioblastoma and anaplastic astrocytoma to evaluate the long-term consequences of radiation therapy and chemotherapy. We defined long-term survivors as those patients with glioblastoma or anaplastic astrocytoma who lived at least 100% longer than median survival of historical controls, for example, 2 years for patients with glioblastoma and 4 years for patients with anaplastic astrocytoma. There were 9 (5.6%) long-term survivors. Three (30%) became demented and died without evidence of tumor recurrence. One, after survival of 10 years, died of tumor recurrence. Of the remaining survivors, 2 (22%) have significantly impaired short-term memory function and other neurological deficits such as gait apraxia. Three (30%) can function independently. It is likely but cannot be proved that it is radiotherapy and not chemotherapy that is the causal factor of this dismal therapeutic outcome. Our study suggests restraint in the use of radiotherapy for patients with brain tumors that have more favorable prognoses than glioblastomas and anaplastic astrocytomas, such as low-grade astrocytomas and oligodendrogliomas.     

Evaluation of ACNU alone and combined with tegafur as additions to radiotherapy of the treatment of malignant gliomas--a cooperative clinical trial

Controlled, prospective, randomized studies were performed to evaluate the effects of 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3- (2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) and ACNU plus tegafur as additions to radiotherapy for the treatment of malignant gliomas. In the first trial, 105 patients with glioblastoma or anaplastic astrocytoma were randomly divided into two groups after surgery and received radiotherapy (RT, 40 to 60 Gy to the whole brain), or radiotherapy plus concomitant chemotherapy with ACNU (100 mg/m2 on day 1 and 42). Effects of the treatment were compared in 82 evaluable patients from results of CT scans taken before and one month after the completion of radiotherapy. The regression rates more than 50% of the tumor size were observed in 15.0% of patients treated with RT alone and in 47.6% of patients treated with RT plus ACNU. The difference was statistically significant (p less than 0.005). In the second trial, 87 patients were randomly divided into two groups and received RT plus ACNU, or RT plus combined chemotherapy with ACNU and tegafur (400 mg/m2, daily for 8 weeks). Sixty-nine patients were within the valid study group. The regression rates more than 50% of the tumor size were observed in 34.2% of patients treated with RT plus ACNU: and in 41.2% treated with RT, ACNU plus tegafur. No statistical difference was noted in the response rate between the groups. These results indicate that ACNU is an effective agent in conjunction with radiotherapy for patients with malignant gliomas, and that tegafur does not enhance the effectiveness of ACNU.     

Concomitant and adjuvant temozolomide of newly diagnosed glioblastoma in elderly patients

Objective

The effect of concomitant and adjuvant temozolomide in glioblastoma patients above the age of 65 years lacks evidence. However, after combined treatment became standard at our center all patients were considered for combined therapy. We retrospectively analyzed the effect of temozolomide focused on elderly patients.

Methods

293 patients with newly diagnosed glioblastoma treated single-centered between 1998 and 2010, by radiation alone or concomitant and adjuvant radiochemotherapy, were included. Treatment groups were analyzed by multi- and univariate analysis. Matched pairs for age, by a 5-year-caliper, extent of resection and general state was generated for all patients and elderly subgroups.

Results

103 patients received radiation only and 190 combined treatment. Multivariate and matched pair analysis revealed a benefit due to combined temozolomide (HR 1.895 and 1.752, respectively). For patients older than 65 years median survival was 3.6 (95% CI 3.2–4.7) and 8.7 months (6.3–11.8) for radiotherapy only and combined treatment (HR 3.097, p < 0.0001, n = 90). Over the age of 70 and 75 years median survival was 3.2 (2.3–4.2) vs. 7.5 (5.1–10.9, HR 4.453, p < 0.0001, n = 62) and 3.2 (1.4–3.9) vs. 9.2 months (4.7–13.5; HR 9.037, p < 0.0001, n = 24), respectively. In 8/56 (14%) patients over the age of 70 years temozolomide was terminated due to toxicity.

Conclusion

Retrospective matched pair analysis gives class 2b evidence for prolonged survival due to concomitant and adjuvant temozolomide in elderly glioblastoma patients. Until prospective data for combined radiochemotherapy in elderly patients will be available concomitant and adjuvant temozolomide therapy should not be withheld.     

人脑胶质瘤中miR-125b和Gli1的表达及临床意义

目的探讨miR-125b在胶质瘤中的表达及其与Gli1的关系。方法收集不同病理级别胶质瘤标本25例,以荧光定量PCR方法检测miR-125b和Gli1的表达,分析miR-125b和Gli1表达水平与胶质瘤病理级别及预后的关系。结果①miR-125b在各级别胶质瘤[星形细胞瘤(0.754±0.085)、间变星形细胞瘤(0.545±0.075)和胶质母细胞瘤(0.340±0.056)]中的表达较正常脑组织(1.000)下调(均P0.05),miR-125b的表达水平与肿瘤的恶性程度呈负相关;②Gli1表达水平在胶质瘤中[星形细胞瘤(1.034±0.093)、间变星形细胞瘤(1.203±0.113)和胶质母细胞瘤(1.578±0.087)]较正常脑组织(1.000)略高,肿瘤的恶性程度与Gli1表达水平呈负相关,间变星形细胞瘤与胶质母细胞瘤比较,差异有统计学意义(P0.05);③miR-125b低表达和Gli1过表达与患者的预后呈负相关。结论 miR-125b低表达和Gli1过表达与恶性胶质瘤的发生、发展密切相关。     

旋转式头部伽玛刀治疗脑转移瘤171例临床分析

目的 探讨旋转式头部伽玛刀在脑转移瘤治疗中的作用及疗效.方法 2010年9月至2011年10月间,我院共有171例脑转移患者接受了放射治疗,其中49人接受单纯全脑放疗（WBRT组）,占28.7％;102例接受了伽玛刀治疗,其中单独伽玛刀治疗（SRS组）50例,占29.2％;伽玛刀联合全脑放疗（WBRT＋ SRS组）72例,占42.1％.WBRT组患者接受全脑放疗40 Gy/20f/4w; SRS组患者接受旋转式头部伽玛刀治疗16 ～ 24 Gy/1f;WBRT＋ SRS组患者接受全脑放疗30 Gy/15f/3 w,后加旋转式头部伽玛刀治疗12 ～16 Gy/1f.观察3组患者的临床效果和并发症,并进行统计处理,分析三组患者的1年局部控制率和1年生存率.结果 3组患者均取得良好效果,未出现严重毒副作用;1年局部控制率分别为52.8％、81.7％、88.1％;1年生存率分别为47.6％、87.8％、92.9％.SRS组、WBRT＋ SRS组1年局部控制率和1年生存率明显高于WBRT组（P＜0.005）,差异有统计学意义;而SRS组和WBRT＋ SRS组1年局部控制率及1年生存率差异无统计学意义（P＞0.10）.结论 单纯头部伽玛刀治疗以及头部伽玛刀联合全脑放疗治疗脑转移瘤,安全有效,较传统的外照射全脑放疗,可以提高患者的生存时间及生存质量.