调强放疗联合替莫唑胺治疗脑胶质瘤术后残余病灶的疗效观察

目的探讨调强放疗(IMRT)联合替莫唑胺(TMZ)治疗脑胶质瘤术后残余病灶的疗效,为临床治疗提供依据。方法选择2012-01—2014-02我院收治的脑胶质瘤患者62例,按照随机数字表法随机分为观察组和对照组,观察组采用IMRT联合TMZ治疗,对照组给予IMRT治疗。比较2组近期和远期临床疗效,并记录不良反应发生情况。结果观察组有效率69.70%显著高于对照组的34.48%,差异有统计学意义(χ~2=7.688,P0.05);观察组半年生存率(78.79%)显著高于对照组(55.17%),差异有统计学意义(χ~2=3.939,P0.05);观察组1a生存率(63.63%)显著高于对照组(37.93%),差异有统计学意义(χ~2=4.084,P0.05)。2组Ⅲ、Ⅳ级恶心呕吐反应、骨髓抑制反应发生差异无统计学意义(χ~2=0.764,P0.05);2组均无严重放射性脑病发生。结论 IMRT联合TMZ治疗脑胶质瘤术后残余病灶,能够显著改善近期和远期临床疗效,且不良反应未明显加重,值得临床推广。     

替莫唑胺联合精确放疗治疗术后脑恶性胶质瘤临床观察

目的通过对比观察替莫唑胺联合精确放疗和单纯精确放疗对术后脑恶性胶质瘤的疗效及安全性。方法选择本院2003-05~2008-11收治的45例术后病理确诊的恶性胶质瘤患者,随机分为实验组21例和对照组24例。实验组在精确放疗同时采用替莫唑胺(TMZ)化疗2个周期,放疗后TMZ巩固治疗2~4个周期;对照组仅行精确放疗。结果实验组的平均无进展生存时间为11.6个月,对照组为7.8个月。实验组的中位生存期为15.7个月,对照组为10.1个月;1、2 a生存率实验组分别为71.4%、38.1%,对照组分别为41.7%、12.5%,2组比较差异有统计学意义(P均<0.05)。2组均未出现严重放射性脑病及胃肠道反应,Ⅲ度及以上骨髓抑制,实验组为23.8%,对照组为16.7%,2组比较差异无统计学意义(P>0.05)。结论 TMZ联合精确放疗提高了术后恶性胶质瘤的中位生存期,1、2 a生存率、毒副作用增加但无显著差别。     

三维适形放疗联合替莫唑胺治疗脑胶质瘤临床观察

目的探讨三维适形放疗联合替莫唑胺治疗脑胶质瘤患者的疗效及对其生活质量的影响。方法选取2013-01—2015-07河南科技大学第一附属医院治疗的84例脑胶质瘤患者,根据治疗方案分为2组各42例。对照组行单纯三维适形放射治疗,观察组在此基础上联合替莫唑胺化疗。统计2组临床疗效及治疗期间不良反应发生率,并对比治疗前后生活质量评分比较,随访1 a,统计1 a后2组生存率。结果观察组治疗总有效率与疾病控制率均高于对照组,差异有统计学意义(P0.05);治疗前,2组生活质量评分差异无统计学意义(P0.05),治疗后观察组生活质量评分高于对照组,差异有统计学意义(P0.05);2组治疗期间未发生Ⅲ～Ⅳ度血液学不良反应,其他不良反应主要表现为白细胞减少(Ⅰ～Ⅱ度)、恶心呕吐(Ⅰ～Ⅱ度)及粒细胞减少(Ⅰ度),且发生率组间比较差异无统计学意义(P0.05),经对症干预后均可缓解,未对治疗产生明显影响;1 a后,观察组生存率高于对照组,差异有统计学意义(P0.05)。结论三维适形放疗联合替莫唑胺化疗对脑胶质瘤的临床效果显著,且有一定安全性,有利于改善患者生活质量,提高生存率。     

替莫唑胺联合放疗治疗脑胶质瘤术后复发患者28例疗效观察

目的 探讨替莫唑胺联合放疗治疗脑胶质瘤术后复发疗效.方法 2008-01～2010-01月收治的脑胶质瘤术后复发患者28例采取替莫唑胺联合放疗治疗疗效.结果 治疗后3个月进行疗效评定,PR 12例,SD 14例,DP 2例,有效率(CR+PR+)92.85％.进行6个月复查时无疾病进展生存率23/28例(82.14％)...     

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。     

三维适形放疗联合替莫唑胺治疗恶性脑胶质瘤术后患者的Meta分析

目的系统评价三维适形放疗联合替莫唑胺（3D-CRT/TMZ）治疗恶性脑胶质瘤术后患者的疗效及安全性。方法检索EMbase、PubMed、Cochrane、中国知网、维普数据库和中国生物医学文献服务数据库等数据库,查找3D-CRT／TMZ治疗恶性脑胶质瘤术后患者的临床随机对照试验,采用RevMan5．2．0软件进行Meta分析。结果共纳入16个研究,共1410例患者。Meta分析结果显示：与3D-CRT相比,3D-CRT／TMZ能显著提高恶性脑胶质瘤术后患者治疗的有效率[优势比（OR）=3．60,95％可信区间（CI）为2．35-5．50,P〈0．00001]、术后1年生存率（OR=3．51,95％CI为2．53～4．87,P〈0．01）、术后2年生存率（OR=3．67,95％CI为（2．61～5．16,P〈0．01）和术后3年生存率（OR=3．73,95％CI为2．44～5．71,P〈0．01）及显著延长患者中位生存时间（平均差异：5．58,95％CI为3．56～7．61,P〈0．01）,但3D-CRT／TMZ不良反应的发生率明显增高（OR=1．54,95％CI为1．14～2．09,P=0．005）。结论3D-CRT/TMZ治疗恶性脑胶质瘤术后患者的有效率、生存率、中位生存时间等疗效显著优于单纯3D-CRT治疗,而不良反应方面高于单纯3D-CRT治疗,但患者一般可耐受。     

替莫唑胺联合放疗治疗Ⅲ～Ⅳ胶质瘤术后的临床研究(附60例临床分析)

目的探讨替莫唑胺联合放疗治疗Ⅲ～Ⅳ胶质瘤术后的临床效果。方法将2012年4月至2015年12月收治的60例Ⅲ～Ⅳ胶质瘤术后患者随机分为对照组与试验组,每组30例。对照组给予单纯放射疗法治疗,试验组加予替莫唑胺口服治疗。检测血清转化生长因子(TGF-β)、胶质纤维酸性蛋白(GFAP),采用Karnofsky(KPS)功能状态量表评估患者机能状态,采用生活质量(quality of life,QOL)评估患者生活质量,比较近期疗效以及长期疗效。结果与治疗前比较,两组血清TGF-β、GFAP水平均显著降低(P0.01),KPS、QOL评分均显著升高(P0.01);与对照组比较,试验组血清TGF-β、GFAP水平均显著较低(P0.01),KPS、QOL评分均显著较高(P0.01);治疗结束后,对照组总有效率63.33%,试验组总有效率73.33%,比较有统计学意义(Z=-2.146,P=0.0320.05);随访至2017年12月,对照组生存率为36.67%(11/31),试验组生存率为60.00%(18/30),经Log-Rank检验有统计学意义(χ~2=3.900,P=0.0480.05)。结论替莫唑胺联合放疗能够提高Ⅲ～Ⅳ胶质瘤术后近远期疗效,值得临床推广应用。     

丘脑胶质瘤的显微手术治疗

目的 探讨丘脑胶质瘤显微外科治疗的安全性和有效性。方法 回顾性分析2014年1月至2017年12月显微手术治疗的11例丘脑胶质瘤的临床资料。结果 肿瘤全切除5例,次全切除4例,大部分切除2例。7例术后症状改善,3例无明显变化,1例加重。无手术死亡病例。11例随访9~27个月;7例因肿瘤复发死亡,中位生存时间12.4个月（9~17个月）;1例术后16个月复发,目前随访19个月仍存活;其余3例临床症状稳定,影像学随访未见肿瘤复发。结论 显微手术是治疗丘脑胶质瘤的有效手段,手术入路需根据术前影像学检查结果个性化制定;熟练掌握显微神经外科技术和辅助技术（包括神经导航、电生理监测等）可降低手术并发症发生率和病死率。     

替莫唑胺应用于恶性脑胶质瘤的研究进展

脑胶质瘤是临床最常见的肿瘤之一,约占颅内肿瘤发病率的40％～50％,由于胶质瘤呈恶性浸润性生长,且多生长在脑重要结构,如基底节、中央沟区、丘脑、脑干等部位,不仅手术难以全切,而且术后易复发。长期以来,单纯手术治疗恶性脑胶质瘤的5年存活率〈25％。但术后合理的放疗、化疗和其他综合治疗可以控制肿瘤生长和延缓复发,使一些病人病情得到较好的改善。化疗作为颅内恶性胶质瘤综合治疗手段之一,已为广大临床医生所接受。替莫唑胺作为一种新型的烷化剂,对恶性脑胶质瘤辅助治疗效果良好。本文就替莫唑胺应用于恶性脑胶质瘤的发展近况作一综述。     

伽玛刀联合替莫唑胺治疗脑胶质瘤的临床观察

目的 探讨伽玛刀联合替莫唑胺和伽玛刀治疗恶性脑胶质瘤的效果和安全性.方法 选择2003～2006年经病理证实为恶性胶质瘤的病人,采用病例对照研究的方法,随机分为二组,实验组(35例)在伽玛刀术后采用替莫唑胺5个周期化疗,对照组(48例)仅行伽玛刀治疗.长期随访,观察病人的无进展生存时间和总的生存时间以及药物的安全性.结果 实验组的平均平均生存期为14.2个月,对照组为7.8个月.实验组的2年生存率为20.5%,对照组为10.1%.常见的不良反应为恶心、呕吐等.结论 伽玛刀联合替莫唑胺治疗恶性胶质瘤有效,能提高生存率而毒副反应小.     

恶性复发性脑胶质瘤术中放射治疗

１０例恶性复发性脑胶质瘤经再次手术加术中放射治疗后，１年生存率为１００％，２年为５０％；再复发中位期间为９个月。本文报告术中放射治疗方法，并对其优点及治疗结果进行讨论。     

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。     

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。     

Hypofractionated intensity modulated radiotherapy with temozolomide in newly diagnosed glioblastoma multiforme

We conducted a phase I study to determine (a) the maximum tolerated dose of peri-radiation therapy temozolomide (TMZ) and (b) the safety of a selected hypofractionated intensity modulated radiation therapy (HIMRT) regimen in glioblastoma multiforme (GBM) patients. Patients with histological diagnosis of GBM, Karnofsky performance status (KPS) ⩾ 60 and adequate bone marrow function were eligible for the study. All patients received peri-radiation TMZ; 1 week before the beginning of radiation therapy (RT), 1 week after RT and for 3 weeks during RT. Standard 75 mg/m²/day dose was administered to all patients 1 week post-RT. Dose escalation was commenced at level I: 50 mg/m²/day, level II: 65 mg/m²/day and level III: 75 mg/m²/day for 4 weeks. HIMRT was delivered at 52.5 Gy in 15 fractions to the contrast enhancing lesion (or surgical cavity) plus the surrounding edema plus a 2 cm margin. Six men and three women with a median age of 67 years (range, 44–81) and a median KPS of 80 (range, 80–90) were enrolled. Three patients were accrued at each TMZ dose level. Median follow-up was 10 months (range, 1–15). Median progression free survival was 3.9 months (95% confidence interval [CI]: 0.9–7.4; range, 0.9–9.9 months) and the overall survival 12.7 months (95% CI: 2.5–17.6; range, 2.5–20.7 months). Time spent in a KPS ⩾70 was 8.1 months (95% CI: 2.4–15.6; range, 2.4–16 months). No instance of irreversible grade 3 or higher acute toxicity was noted. HIMRT at 52.5 Gy in 15 fractions with peri-RT TMZ at a maximum tolerated dose of 75 mg/m²/day for 5 weeks is well tolerated and is able to abate treatment time for these patients.     

Long-term treatment with temozolomide in malignant glioma

Six months of maintenance temozolomide (TMZ) following concurrent TMZ chemotherapy and radiation therapy has become the standard of care in the treatment of glioblastoma. In addition, TMZ has also been used to treat other forms of glioma although less evidence of efficacy exists. TMZ administration longer than 6 months is common in clinical practice, but it is unusual for the drug to be administered longer than 1 to 2 years. We report five patients who received long-term treatment with TMZ chemotherapy at normal dosing levels. One of these patients was diagnosed with glioblastoma, two with anaplastic astrocytoma, one with gliosarcoma, and one with oligo-astrocytoma. The length of treatment in our group of patients ranged from 45 to 85 cycles of TMZ. Common Terminology Criteria for Adverse Events (CTCAE) developed by The National Cancer Institute was used to classify toxicity. Two patients experienced no toxicity per CTCAE guidelines. One patient experienced grade I thrombocytopenia, one developed grade I leukopenia, and one experienced both grade I thrombocytopenia and grade I nausea, all which resolved with either withholding TMZ for 1 month or supportive treatment. Our report provides evidence that long-term TMZ chemotherapy is a therapeutic option when appropriately monitored.     

Rechallenge with temozolomide in patients with recurrent gliomas

Temozolomide (TMZ) is the standard of care for patients with newly diagnosed glioblastoma (GBM) as well as those with recurrent anaplastic glioma (AG) and GBM. It has become common practice to re-expose patients to TMZ who had been previously treated with TMZ, or to switch patients to alternative dosing regimens of TMZ when there are signs of relapse or progress on standard TMZ therapeutic regimens. To date, however, there is a scarcity of data on the efficacy of this therapeutic strategy, currently referred to as TMZ rechallenge. We have conducted a retrospective review of patients with recurrent glioma rechallenged with TMZ. Patients experiencing progressive disease (PD) during TMZ therapy who were rechallenged with alternative TMZ regimens and patients rechallenged after stable disease in a TMZ-free interval were evaluated separately. A total of 90 rechallenges were identified in 80 patients. The progression-free survival at 6 months (PFS-6) was 48% in patients with AG (12/25) and 27.7% in those with GBM (14/47). The PFS-6 was 16.7% in AG and 26.3% in GBM for patients switched during TMZ and 57.9 and 28.6% in patients rechallenged after a TMZ-free interval of at least 8 weeks. Relevant hematological toxicity (NCI-CTC grade 3–5) was observed in 22 of 90 rechallenges, and relevant non-hematological in ten of 90 rechallenges. Temozolomide was well tolerated and generated promising PFS-6 in patients who had previously failed TMZ, regardless if they progressed during TMZ treatment, or if they were rechallenged after a TMZ-free interval. These results suggest that the TMZ rechallenge strategy warrants further investigation in a prospective randomized trial.     

恶性脑胶质瘤综合治疗的疗效观察

目的探讨综合治疗恶性脑胶质瘤患者的疗效。方法对80例恶性脑胶质瘤患者资料进行回顾性分析,其中手术＋外放疗＋化疗23例;手术＋外放疗21例;手术＋内放疗17例;手术＋化疗19例。比较各组生存率、无进展生存时间和总生存时间。结果手术＋外放疗＋化疗组的年生存率明显高于其他组;其平均无进展生存时间为（56．33±3．36）周,手术＋外放疗组为（45．72±3．74）周,手术＋内放疗组为（46．83±4．55）周,手术十化疗组为（41．5±3．95）周。手术＋外放疗＋化疗组的平均总生存时间为（62．27±3．19）周,手术＋外放疗组为（56．33±3．74）周,手术＋内放疗组为（54．19±4,80）周,手术＋化疗组为（47．65±3．97）周。结论手术＋外放疗＋化疗是恶性脑胶质瘤的有效治疗方法。     

Role of temozolomide in pediatric brain tumors

Features of temozolomide Temozolomide (TMZ) belongs to the imidazotetrazine class and it is a DNA-methylating agent that has a good antitumor activity. Despite of dacarbazine, TMZ is spontaneously converted into its active metabolite 5-(3-methyltriazen-l-yl)imidazole-4-carboxamide at physiologic pH, so it is not required in enzymatic demethylation in the liver. TMZ is able to cross the blood brain barrier and is stable at gastric acid pH so it has almost 100% oral bioavailability and is rapidly absorbed after it is taken orally.Temozolomide in cancer patients On the basis of the relatively safe toxicity and the findings achieved in adult malignant gliomas, phase I and II clinical trials were set up to evaluate the opportunity of using this novel drug in pediatric cancer, too. In this review, we evaluate the antitumor activity of TMZ against high-grade gliomas, low-grade-gliomas, and medulloblastoma/primitive neuroectodermal tumors analyzing several phases I and II clinical trials in children.Conclusions In spite of the poor activity of TMZ against pediatric brain tumors, the use of the drug in combination with other compounds should be evaluated in phases I and II clinical trials. Moreover, the evaluation of the methylation status of the O6-methylguanine DNA methyltransferase promoter in glioblastoma biopsy specimens could be assayed as a predictive factor of TMZ efficacy.     

胶质瘤的靶向性基因治疗进展

在胶质瘤的基因治疗中，利用脑胶质瘤组织中相对特异性的标志物如表皮生长因子受体、端粒及端粒酶等实现目的基因在肿瘤组织的靶向性表达；同时对病毒载体进行重组，对肿瘤血管生成的抑制等实现选择性地、高效地对肿瘤组织的转染。