高级别脑胶质瘤术后三维适形放疗联合替莫唑胺化疗的疗效观察

背景与目的：国外已有同期放，化疗治疗高级别脑胶质瘤成功经验。本研究观察术后三维适形放疗加替莫唑胺同步和辅助化疗治疗高级别脑胶质瘤的近期疗效和不良反应。方法：收集2003年1月至2006年12月收治的21例高级别脑胶质瘤部分切除术后患者，行三维适形放疗[2．0Gy／（次·d），5d／周，总剂量60～70Gy]，替莫唑胺同步化疗6～7周＋辅助化疗3～6疗程。结果：本组21例患者有效率为81．0％。6个月无疾病进展生存率为76．2％（16121），1年无疾病进展生存率52．4％（11／21），1年生存率为71．4％（15／21）；患者对治疗的耐受性良好，常见的不良反应为头痛、恶心、呕吐和乏力。结论：高级别脑胶质瘤术后三维适形放疗联合替莫唑胺化疗近期疗效良好。且患者对治疗的耐受性好，是切实可行的治疗方案。     

脑胶质瘤诊疗进展

尽管目前脑胶质瘤的诊断随着WHO诊断指南的更新在不断改变,但是目前的治疗方法依然以手术治疗为主、辅以放疗和化疗。高级别脑胶质瘤的治疗效果仍不如人意,如何改善患者预后是目前医学探索脑胶质瘤领域的重点问题。目前脑胶质瘤的诊疗研究涌现出许多新思路、新方法,其中以电场治疗为代表的一部分临床试验取得了较好的效果,此外,免疫治疗领域和靶向治疗领域也有了一定的进展。本文旨在分享、探讨这些新方法,总结脑胶质瘤诊疗进展。     

高级别脑胶质瘤的放疗进展

高级别脑胶质瘤(WHO Ⅲ、Ⅳ级胶质细胞瘤)是成人最常见的颅内恶性肿瘤,约占颅内原发恶性肿瘤的35%~45%。肿瘤没有完整包膜,呈浸润性生长,与正常脑组织分界不清。手术难以完全切除,术后放疗和化疗是重要的辅助治疗手段,可以明显改善患者生存。随着同期放化疗作为标准治疗模式的出现以及精确放疗时代的到来,近年来关于照射范围、术后开始放疗时间、放疗剂量及分割方式等方面问题仍存在很大争议。本文就这些问题综述如下。     

替莫唑胺联合放疗治疗18例初诊高级别脑胶质瘤患者的临床观察

背景与目的:高级别脑胶质瘤(HGG)病程发展快,死亡率高,寻找新的治疗方法和开发新的化疗药物成为目前这种疾病研究的热点.本研究通过观察替莫唑胺同步放疗加单药辅助化疗治疗初诊高级别脑胶质瘤的疗效和安全性,对替莫唑胺一线治疗脑胶质瘤的临床获益性进行探讨.方法:采用60Co对18例HGG患者进行全脑(DT 40 Gy/20 f)加局部小野(DT 20 Gy/10 f)照射DT 60 Gy/30 f×6周,放疗期间每日口服替莫唑胺75 mg/m2,放疗结束后4周,继续给予替莫唑胺标准5 d方案辅助化疗6个周期,每一周期28 d.第1周期用量150 mg/m2,连用5 d,无明显血液毒性后,从第2周期起剂量增至200 mg/m2.结果:18例高级别脑胶质瘤患者中位随访12.5个月,11例出现复发或进展,5例死亡.中位疾病无进展生存期为9.8个月(95%CI,6.1～9.8个月),中位总生存时间为14个月(95%CI,8.5～19.5个月),1年总生存率为55.6%,6个月疾病无进展生存率为81.8%.替莫唑胺不良反应发生率低,以轻度血液毒性为主.结论:替莫唑胺联合同步放疗加后续单药辅助化疗治疗初诊高级别脑胶质瘤有较好的临床疗效,本疗法安全性好,患者能够从中受益.     

高级别脑胶质瘤术后同步加量与序贯加量调强放疗疗效比较北大核心CSCD

目的探讨高级别脑胶质瘤术后同步加量调强放疗和术后序贯加量调强放疗的疗效及不良反应。方法回顾性分析2010年1月至2017年12月连续住院行术后放疗的高级别脑胶质瘤患者142例,根据治疗方式分为同步加量调强放疗及序贯加量调强放疗两组,两组放疗期间均给予替莫唑胺同步化疗,对比两组患者的随访情况。结果全组的中位总生存(OS)为24个月,中位无进展生存(PFS)为17个月,中位无瘤生存(DFS)为25个月;同步加量放疗组与序贯加量放疗组的中位OS分别为27.2个月和21个月(P=0.950),中位PFS分别为21.2个月与15个月(P=0.21),中位DFS分别为28个月与18个月(P=0.171),疾病控制率分别为92.86%与85.17%(P=0.541),两组OS、PFS、DFS、近期疗效及不良反应方面差异均无统计学意义,但同步加量组的适形性优于序贯加量组(P=0.032)。结论高级别脑胶质瘤术后同步加量对比序贯加量调强放疗,在生存期、近期疗效及治疗不良反应方面差异均无统计学意义,但同步加量组适形性明显更好,可推荐用于高级别脑胶质瘤术后放疗。     

替莫唑胺化疗联合放疗治疗高级别脑胶质瘤的疗效及其对血清标志物的作用

目的 探究替莫唑胺化疗联合放疗治疗高级别脑胶质瘤的疗效及其对血清标志物的作用.方法 将82例高级别脑胶质瘤患者按照治疗方式的不同分为单一放疗组与联合化疗组,每组41例.单一放疗组采用常规术后放疗,联合化疗组在单一放疗组的基础上给予替莫唑胺化疗.比较两组患者治疗前后的血管内皮生长因子(VEGF)水平、表皮生长因子(EGF)水平、T淋巴细胞亚群水平、卡氏功能状态(KPS)评分和生活质量(QOL)评分、蒙特利尔认知评估量表(MoCA)评分及近期临床疗效.结果 治疗后,联合化疗组患者VEGF、EGF水平均明显低于单一放疗组(P﹤0.01),CD8+明显低于单一放疗组(P﹤0.01),CD3+、CD4+、CD4+/CD8+均明显高于单一放疗组(P﹤0.01),KPS、QOL、MoCA评分均明显高于单一放疗组(P﹤0.01).联合化疗组患者总有效率为90.24％,高于单一放疗组的75.61％,差异有统计学意义(P﹤0.05).联合化疗组患者不良反应总发生率为7.32％,明显低于单一放疗组的24.39％,差异有统计学意义(P﹤0.01).结论 替莫唑胺化疗联合放疗治疗高级别脑胶质瘤,可降低对患者认知功能造成的影响,改善患者的T淋巴细胞亚群水平及血清标志物水平.     

脑胶质瘤术后立体定向放射治疗(SFR)疗效观察

目的回顾性分析脑胶质瘤术后多分割立体定向放射治疗(SFR)的疗效。方法16例脑胶质瘤术后患者,8例行常规放疗(RT) 立体定向放疗,8例单行立体定向放疗。肿瘤剂量(DT)(57.72±10.33)Gy。结果低分级脑胶质瘤(I、II级)1、2、3年生存率为100%(6/6)、100%(6/6)、83.3%(5/6),高分级脑胶质瘤(III、IV级)1、2、3年生存率为80%(8/10)、70%(7/10)、50%(5/10)。结论采用多分割立体定向放射治疗治疗脑胶质瘤有较好的临床疗效,是控制肿瘤生长及延迟复发的重要辅佐治疗手段。     

贝伐单抗治疗高级别脑胶质瘤的研究进展

脑胶质瘤中3/4以上的患者为高级别脑胶质瘤,其恶性程度高,术后易复发,预后极差。虽然术后同步放化疗能使高级别脑胶质瘤患者生存获益,但其仅能延长有限的生存时间。近年来,肿瘤的分子靶向治疗逐渐成为研究热点。血管内皮生长因子在脑胶质瘤及其周围组织中高表达,调控着肿瘤的生长过程,是脑胶质瘤治疗的有效靶点。贝伐单抗能够特异性地阻止血管内皮生长因子与其受体结合,抑制肿瘤血管的形成;同时还能使肿瘤血管正常化,改善血管通透性,增加肿瘤组织有效药物浓度,从而达到其抗肿瘤的作用。本文就贝伐单抗的作用机制及近些年贝伐单抗单药与联合化疗或其他药物治疗高级别脑胶质瘤的研究进展进行综述。      

多模态MRI在高级别脑胶质瘤放疗中的应用

放疗是高级别脑胶质瘤治疗的重要手段之一。目前,对于利用定位CT和常规MRI图像进行靶区勾画的范围仍然没有统一标准。随着影像学技术的不断发展,研究者们发现利用多模态MRI包括氢质子磁共振波谱分析(¹H-MRS)、BOLD-fMRI (血氧水平依赖性功能磁共振)、弥散加权成像(DWI)、弥散张量成像(DTI)等可更有效地评估肿瘤的浸润范围及定位周围重要组织,从而作为一种补充手段应用于靶区勾画和保护危及器官之中。此外,多模态MRI对评估放疗疗效、探测放射损伤及鉴别真假性进展也有一定作用。文章就多模态MRI在高级别脑胶质瘤术后放疗中应用作一综述。     

HSV-TK/GCV自杀基因系统联合不同分割剂量照射对人胶质瘤细胞的实验研究

脑胶质瘤对常规分割放疗的疗效较差,促使人们探索非常规分割放疗的价值.自杀基因治疗被认为是肿瘤基因治疗最有前景的策略之一,而肿瘤基因-放疗是近年提出的肿瘤治疗新思路.单纯疱疹病毒(herpes simplex virus,HSV)-胸苷激酶(thymidine kinase,TK)(HSV-TK)/鸟嘌呤(ganciclovir,GCV)(HSV-TK/GCV)自杀基因系统治疗脑胶质瘤已进入临床Ⅲ期实验,但仍存在不足之处[1].Rogulski等[2]实验证明HSV-TK/GCV系统均能提高肿瘤对放射的敏感性.笔者通过逆转录病毒介导将HSV-TK转入人胶质瘤细胞系U251(U251/TK细胞)后联合不同分割方式照射,观察其杀伤效应,为临床改进胶质瘤治疗方案提供理论基础.     

A Systematic Overview of Radiation Therapy Effects in Brain Tumours

A systematic review of radiation therapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for evaluation of the scientific literature are described separately (Acta Oncol 2003; 42: 357-365). This synthesis of the literature on radiation therapy for brain tumours is based on data from 9 randomized trials and 1 meta-analysis. Moreover, data from 2 prospective studies, 3 retrospective studies and 4 other articles were used. In total, 19 scientific articles are included, involving 4 266 patients. The results were compared with those of a similar overview from 1996 including 11 252 patients. The conclusions reached can be summarized as follows: The conclusion from SBU 129/2 that curative treatment is not available for patients with high-grade malignant glioma (grade III and IV) is still valid.The survival benefit from postoperative radiotherapy compared to supportive care only or chemotherapy is about 3-4 months, as demonstrated in earlier randomized studies.

Quality of life is now currently estimated and considered to be of major importance when reporting the outcome of treatment for patients with brain tumours.

There is no scientific evidence that radiotherapy using hyper- and hypofractionation leads to longer survival for patients with high-grade malignant glioma than conventional radiotherapy. There is large documentation, but only one randomized study.There is some documentation to support the view that patients with grade IV glioma and poor prognosis can be treated with hypofractionation and with an outcome similar to that after conventional fractionation. A shorter treatment time should be convenient for the patient.Documentation of the benefit of a radiotherapy boost with brachytherapy is limited and no conclusion can be drawn.There is no scientific evidence that radiotherapy prolongs life for patients with low-grade glioma.There are some data supporting that radiotherapy can be used to treat symptoms in patients with low-grade glioma. As no controlled studies have been reported, no firm conclusion can be drawn.     

Silencing of R-Spondin1 increases radiosensitivity of glioma cells

Although radiation therapy is the most effective postoperative adjuvant treatment, it does not substantially improve the long-term outcomes of glioma patients because of the characteristic radioresistance of glioma. We found that R-Spondin1 (Rspo1) expression was elevated in high-grade gliomas and was associated with worse overall survival and disease-free survival. Rspo1 expression was also associated with reduced survival rates in glioma patients after treatment with radiotherapy and temozolomide (RT-TMZ). Importantly, Rspo1 was dramatically upregulated after radiation treatment in patients with glioma. Rspo1 silencing by shRNA potentiated glioma cell death upon radiation treatment. In a xenograft nude mouse model, combining radiation and silencing of Rspo1 potentiated tumor growth inhibition. Thus, combining radiotherapy with silencing of Rspo1 is a potential therapeutic approach.     

脑胶质瘤术后放疗疗效及预后影响因素分析

目的探讨脑胶质瘤术后放疗疗效及预后影响的相关性因素。方法将脑胶质瘤患者性别、年龄、切除程度、级别、手术放疗时间、放疗方式、肿瘤直径、术前KPS评分、术前水肿情况、放疗剂量纳入研究,计算上述指标与胶质瘤术后放疗疗效的相关性。结果患者治疗后1年、2年、3年的生存率分别为82．9％（126／152）、57．9％（88／152）、32．2％（49／152）。单因素分析结果显示,患者年龄、切除程度、级别、手术放疗时间、术前KPS评分为影响脑胶质瘤术后放疗疗效的相关因素。COX多因素分析显示,年龄、KPS评分、手术切除程度对脑胶质瘤患者预后具有影响。结论手术联合放疗对脑胶质瘤具有明显的手术疗效,年龄、KPS评分、手术切除程度对脑胶质瘤患者预后具有影响。     

A systematic overview of radiation therapy effects in brain tumours

A systematic review of radiation therapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for evaluation of the scientific literature are described separately (Acta Oncol 2003; 42: 357-365). This synthesis of the literature on radiation therapy for brain tumours is based on data from 9 randomized trials and 1 meta-analysis. Moreover, data from 2 prospective studies, 3 retrospective studies and 4 other articles were used. In total, 19 scientific articles are included, involving 4,266 patients. The results were compared with those of a similar overview from 1996 including 11,252 patients. The conclusions reached can be summarized as follows: The conclusion from SBU 129/2 that curative treatment is not available for patients with high-grade malignant glioma (grade III and IV) is still valid. The survival benefit from postoperative radiotherapy compared to supportive care only or chemotherapy is about 3-4 months, as demonstrated in earlier randomized studies. Quality of life is now currently estimated and considered to be of major importance when reporting the outcome of treatment for patients with brain tumours. There is no scientific evidence that radiotherapy using hyper- and hypofractionation leads to longer survival for patients with high-grade malignant glioma than conventional radiotherapy. There is large documentation, but only one randomized study. There is some documentation to support the view that patients with grade IV glioma and poor prognosis can be treated with hypofractionation and with an outcome similar to that after conventional fractionation. A shorter treatment time should be convenient for the patient. Documentation of the benefit of a radiotherapy boost with brachytherapy is limited and no conclusion can be drawn. There is no scientific evidence that radiotherapy prolongs life for patients with low-grade glioma. There are some data supporting that radiotherapy can be used to treat symptoms in patients with low-grade glioma. As no controlled studies have been reported, no firm conclusion can be drawn.     

Durable response of a radiation-induced,high-grade cerebellar glioma to temozolomide

Summary Background Radiation-induced high-grade gliomas are a rare but serious late complication of radiotherapy. We report a patient with radiation-induced cerebellar high-grade glioma who had a durable response to temozolomide. Patients and Methods Case report of a 77-year-old woman with a radiation-induced, high-grade cerebellar glioma that responded durably to temozolomide. Results Our patient developed a cerebellar high-grade glioma 9 years after treatment for a stage IV (T4N0M0) supraglottic laryngeal squamous cell carcinoma with cisplatinum and fluorouracil chemotherapy, and subsequently focal head and neck radiotherapy. Patient was treated with radiation and concurrent temozolomide (only partially due to toxicity) and was stable for 1 year without further adjuvant treatment. Subsequently the tumor recurred and the patient had a dramatic and durable response to standard 5 day dosing of adjuvant temozolomide. Conclusion High-grade gliomas are a late complication of radiation to the central nervous system and may respond to chemotherapy.     

Estimation of radiobiologic parameters and equivalent radiation dose of cytotoxic chemotherapy in malignant glioma

PURPOSE: To determine the radiobiologic parameters for high-grade gliomas. METHODS AND MATERIALS: The biologic effective dose concept is used to estimate the alpha/beta ratio and K (dose equivalent for tumor repopulation/d) for high-grade glioma patients treated in a randomized fractionation trial. The equivalent radiation dose of temozolomide (Temodar) chemotherapy was estimated from another randomized study. The method assumes that the radiotherapy biologic effective dose is proportional to the adjusted radiotherapy survival duration of high-grade glioma patients. RESULTS: The median tumor alpha/beta and K estimate is 9.32 Gy and 0.23 Gy/d, respectively. Using the published surviving fraction after 2-Gy exposure (SF2) data, and the above alpha/beta ratio, the estimated median alpha value was 0.077 Gy(-1), beta was 0.009 Gy(-2), and the cellular doubling time was 39.5 days. The median equivalent biologic effective dose of temozolomide was 11.03 Gy(9.3) (equivalent to a radiation dose of 9.1 Gy given in 2-Gy fractions). Random sampling trial simulations based on a cure threshold of 70 Gy in high-grade gliomas have shown the potential increase in tumor cure with dose escalation. Partial elimination of hypoxic cells (by chemical hypoxic cell sensitizers or carbon ion therapy) has suggested that considerable gains in tumor control, which are further supplemented by temozolomide, are achievable. CONCLUSION: The radiobiologic parameters for human high-grade gliomas can be estimated from clinical trials and could be used to inform future clinical trials, particularly combined modality treatments with newer forms of radiotherapy. Other incurable cancers should be studied using similar radiobiologic analysis.     

Combined Radio- and Chemotherapy of Brain Tumours in Adult Patients

In order to examine the current standards of care regarding combined radio- and chemotherapy for adult patients with brain tumours, a review was carried out of recent studies examining surgery, radiotherapy and chemotherapy in high-grade glioma, medulloblastoma and primary central nervous system lymphoma. The integration of the oral cytotoxic agent temozolomide into current treatment protocols of postoperative combination therapy with radiation and drugs in high-grade glioma is discussed. In glioblastoma, the landmark phase III trial by the European Organisation for Research and Treatment of Cancer and the National Cancer Institute of Canada has defined the current standard of care. Attempts to optimise the schedule of temozolomide administration and to combine this regimen with additional agents are currently ongoing. Additional trials are examining whether temozolomide–radiotherapy combination regimens should also be the standard of care in patients with anaplastic glioma. The role of postsurgery procarbazine, lomustine, and vincristine (PCV) in addition to radiotherapy in anaplastic glioma with oligodendroglial features is controversial, as two randomised trials failed to show improved survival, despite longer progression-free survival. In medulloblastoma, no comparable landmark trial exists and therefore combined radiochemotherapy must be considered investigational. In primary central nervous system lymphoma, high-dose methotrexate-based chemotherapy is the cornerstone of therapy and the value of consolidation radiotherapy for patients achieving a complete response is controversial, even in younger patients who have a lower risk of neurotoxicity than older patients. The challenges associated with brain tumour treatment remain formidable, but rationally designed clinical trials are gradually leading to improved outcomes.     

Recent advancements in multimodality treatment of gliomas

Gliomas account for the vast majority of malignant adult brain tumors. Even though tremendous effort has been made to optimize treatment of patients with high-grade glioma, the prognosis remains poor, especially for patients with glioblastoma. The dismal prognosis conferred by these tumors is in part caused by the tendency to diffusely infiltrate into neighboring brain tissue, but also by the inherent resistance of these tumors to both chemotherapy and radiation. This article reviews the recent advancements in multimodality treatment of patients with gliomas, both in the primary and recurrent setting, with an emphasis on the emerging targeted therapies. Moreover, the external beam radiotherapy options, including intensity modulated radiotherapy and particle (proton and carbon ion) radiotherapy are reviewed.     

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。