PET-CT在脑胶质瘤放射治疗及随访中的应用和研究进展北大核心CSCD

脑胶质瘤是颅内最常见的原发性中枢神经系统肿瘤,术后放疗是其重要治疗手段。目前CT和MRI在脑胶质瘤放疗靶区设计中被广泛应用,但对于肿瘤范围、复发、放射性坏死、预后等方面的评估仍然存在一定不足。正电子发射断层显像(PET)-CT将PET的分子影像与CT的解剖结构影像融于一体,在脑胶质瘤的诊断和鉴别诊断中具有重要价值。随着多模态影像技术在放疗中推广应用,PET-CT分子影像作为重要的补充,有助于脑胶质瘤靶区的勾画和精准放疗的开展,有益于脑胶质瘤患者的预后和随访。本文对PET-CT在脑胶质瘤诊断、治疗及随访中的应用和研究进展进行综述。     

PET-CT在脑胶质瘤放射治疗及随访中的应用和研究进展

脑胶质瘤是颅内最常见的原发性中枢神经系统肿瘤, 术后放疗是其重要治疗手段。目前CT和MRI在脑胶质瘤放疗靶区设计中被广泛应用, 但对于肿瘤范围、复发、放射性坏死、预后等方面的评估仍然存在一定不足。正电子发射断层显像(PET)-CT将PET的分子影像与CT的解剖结构影像融于一体, 在脑胶质瘤的诊断和鉴别诊断中具有重要价值。随着多模态影像技术在放疗中推广应用, PET-CT分子影像作为重要的补充, 有助于脑胶质瘤靶区的勾画和精准放疗的开展, 有益于脑胶质瘤患者的预后和随访。本文对PET-CT在脑胶质瘤诊断、治疗及随访中的应用和研究进展进行综述。     

70例脑胶质瘤术后放疗生存率分析

脑胶质瘤来源于神经胶质，是最常见的中枢神经系统肿瘤，占颅内肿瘤的40％。目前对脑胶质瘤的治疗仍以手术为主，但无法提高生存率。近年手术后的配合放疗有些报道。现将我院1989年8月至1991年8月脑胶质瘤术后放疗资料小结如下。1资料临床资料资料来自我科经病理确诊的脑胶质瘤     

^32P,147Pm对人脑胶质瘤细胞作用

颅内肿瘤在我国居民发病率为1.34/10万,脑胶质瘤约占颅内肿瘤的43％。恶性胶质瘤自然病程从出现症状至死亡平均存活期不到一年。恶性胶质瘤患者术后放疗生存期高于单纯手术治疗。对脑干、丘脑、第三脑室等手术难以达到部位的肿瘤,放疗更具有独特的效果。近年来有人报导采用~(32)P、~(198)Au颅内注射治疗脑胶质瘤。内照射治疗的效果主要取决于选择的核素种类和剂量。为此我们采     

影响脑胶质瘤放疗预后因素的分析

脑胶质细胞瘤约占原发性中枢神经系统肿瘤的40％～53％，临床上传统多采用手术治疗，但由于其呈浸润性生长，大多与正常脑组织无明显分界，手术难以做到彻底切除，生存率较低，故放疗成了提高疗效、改善预后的重要手段。目前由于不同肿瘤医院在病例的选择、显微外科手术的应用、放疗技术的运用以及统计学方法的采用等方面存在差异，影响脑胶质瘤术后放射治疗的预后因素也有所不同。据文献报道，与胶质瘤预后有关的因素包括年龄、病理分级或类型、症状持续时间、手术切除范围、放疗前或后的功能状态、等待放疗时间以及放疗剂量等。本文对影响脑胶质瘤放射治疗预后的独市因素进行综述。     

放射线诱发颅内肿瘤

放射线可在人类和实验动物的许多器管内诱发肿瘤,特别是骨髓一类组织更是如此,但中枢神经系统却有较大的抵抗力Hirosbima 和Nagasaki 的报告证实了这一点,然而近来报告对良性病变和头癣的放射治疗,诱发了中枢神经系统肿瘤。近二、三十年来,放射治疗原发性中枢神经系统恶性肿瘤卓有成效患者并能长期存活。但放射后又可继发中枢神经系统肿瘤偶发,主要为肉瘤和脑膜瘤,神经胶质瘤少见。本文报告三例放疗诱发的肿瘤,其中两例是神经胶质瘤。(见表1)     

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。     

多形性胶质母细胞瘤的适形放疗新进展

多形性胶质母细胞瘤(glioblastoma multiforme, GBM)是最常见的脑胶质瘤之一,为高分级脑胶质瘤,放疗是其重要的治疗手段。Chang等研究表明,接受肿瘤局部放疗患者的中位生存时间(7个     

中国胶质瘤规范化治疗现状

<正>脑胶质瘤是最常见的原发性颅内肿瘤,约占中枢神经系统肿瘤的31%,且近30年来发生率逐年递增。恶性胶质瘤(WHO分类Ⅲ、Ⅳ级)约占所有胶质瘤的77.5%,是34岁以下肿瘤患者的第2位死亡原因,其5年病死率在全身肿瘤中列第三位,仅次于胰腺癌和肺癌[1]。胶质瘤最大的生物学特性是肿瘤细胞呈浸润性生长,难以全切,术后易复发,     

miR-210/VMP1信号传导通路在脑胶质瘤中作用的研究进展

脑胶质瘤是目前临床上最常见的中枢神经系统恶性肿瘤之一,全球发病率约为每年7/10万。在我国胶质瘤的发病率占据颅内肿瘤第一位。临床上胶质瘤的治疗手段主要为手术切除,但是术后复发率高、生存期短,通常只有15～19个月。因此对于胶质瘤寻找有效的治疗靶点,在临床上就显得尤为重要。有研究表明胶质瘤患者脑组织中miR-210水平明显高于正常脑组织,且表达越高患者预后越差。空泡膜蛋白1(vacuole membrane protein 1,VMP1)为大分子跨膜蛋白,研究发现VMP1在蛋白分泌、细胞器形成及多细胞发育过程中起重要作用,另外在人体许多肿瘤组织中如乳腺癌、肾癌、肝癌等均有表达,且在原发与转移性肿瘤中表达不一致,被预测其可能是一个肿瘤相关蛋白,但其在胶质瘤中的机制目前仍未涉及到。故本文简要综述当前miR-210/VMP1信号传导通路在胶质瘤中作用机制的研究进展。     

Chemotherapy for brain tumors of astrocytic and oligodendroglial lineage: the past decade and where we are heading

Over the past three decades, we have made great strides in the treatment of most, but not all, brain tumors. Dramatic advances have occurred in diagnostic imaging, neurosurgery, neuroanesthesia, radiotherapy, and chemotherapy for CNS tumors. Unfortunately, our progress has not yet met our expectations. Because of the infiltrative nature of most primary brain tumors, neurosurgery can never be expected to be curative for the majority of gliomas. Because infiltrative tumors interdigitate with normal brain cells and are not highly sensitive to irradiation, one cannot expect radiotherapy to be curative without serious damage to normal brain cells. The hope for a cure, then, rests with chemotherapy. Those who administer chemotherapy to patients with CNS tumors fully expect that, in time, long-term survival and, ultimately, the cure will become an everyday reality. To achieve that reality, however, new treatment concepts and drugs are needed.     

Somatostatin receptor subtype 2 is expressed by supratentorial primitive neuroectodermal tumors of childhood and can be targeted for somatostatin receptor imaging.

PURPOSE: Although gliomas predominate among central nervous system (CNS) neoplasms in adulthood, embryonal tumors are the most common malignant brain tumors in children. Despite novel treatment approaches, including improved radiotherapy and high-dose chemotherapy, survival rates remain unsatisfactory. The timely diagnosis of residual or recurrent embryonal CNS tumors and thus the earliest possible time point for intervention is often hampered by inaccuracies of conventional imaging techniques. Novel and refined imaging methodologies are urgently needed. EXPERIMENTAL DESIGN: We have previously demonstrated the use of somatostatin receptor imaging (SRI) in the diagnosis of recurrent and residual medulloblastomas. Here, we evaluated somatostatin receptor type 2 (sst(2)) expression using an antibody in an array of CNS tumors of childhood. Eight high-grade gliomas, 4 atypical teratoid/rhabdoid tumors, 7 supratentorial primitive neuroectodermal tumors (stPNET), 1 medulloepithelioma (ME), and 8 ependymomas were screened. Tumors positive in vitro were additionally analyzed in vivo using SRI. RESULTS: Abundant expression of somatostatin receptor type 2 in stPNET, a ME, and ependymomas warranted in vivo imaging of 7 stPNET, 1 rhabdomyosarcoma, 3 ependymomas, 1 ME, and 1 glioblastoma. Although SRI was positive in 6/7 stPNET, 1 rhabdomyosarcoma, and 1 ME, none of the ependymomas nor the glioblastoma could be imaged using SRI. In selected cases SRI was more sensitive in the detection of relapse than conventional imaging by magnetic resonance imaging and computed tomography. CONCLUSIONS: SRI should be considered in the evaluation of residual or recurrent embryonal CNS tumors, especially stPNET. The strengths of SRI lie in the differentiation of reactive tissue changes versus residual or recurrent tumor, the detection of small lesions, and possibly in the distinction of stPNET from gliomas.     

Chemo-radiotherapy for malignant brain tumors

I) Malignant gliomas: Randomized clinical trials conducted in the USA showed that radiotherapy plus chemotherapy with nitrosoureas offered a long-term survival advantage to patients younger than 60 years old with malignant gliomas. Combination chemotherapy, such as procarbazine/CCNU/vincristine (PCV) must be tested further, and intra-arterial chemotherapy with nitrosoureas offered no survival advantage. Combination chemotherapy with PCV showed efficacy for patients with anaplastic oligodendroglioma and anaplastic oligoastrocytoma. II) Medulloblastoma: The addition of chemotherapy to radiotherapy improved the survival of patients with poor risk medulloblastoma, and may reduce the required craniospinal radiation dose in patients with good risk medulloblastoma. III) Primary CNS lymphoma (PCNSL): Combination of chemotherapy with high-dose MTX and radiotherapy improved survival of patients with PCNSL; however, the neurotoxicity produced by this treatment modality is a serious problem in older patients. IV) Intracranial germ cell tumors: The addition of chemotherapy to radiotherapy may produce long term survival with good quality of life in patients with germinoma. Neoadjuvant therapy consisting of chemotherapy and radiotherapy followed by complete surgical excision improved survival of patients with intracranial nongerminomatous germ cell tumors.     

The changing management of low-grade astrocytomas and oligodendrogliomas

Low-grade gliomas are uncommon primary brain tumors that preferentially affect young to middle-aged adults. Although they are indolent tumors, low-grade gliomas cause considerable and progressive morbidity and are ultimately fatal. Surgery and radiotherapy are the primary therapeutic options for patients with these diseases. Chemotherapy is playing a larger role in the management of patients with low-grade gliomas. Patients with oligodendrogliomas or other low-grade gliomas that harbor a distinct genetic derangement characterized by allelic loss of chromosomes 1p and 19q appear to have a superior prognosis that is due in part to a more predictable and durable response to treatment. For this subset of patients with low-grade gliomas, treatment with initial chemotherapy and deferred radiotherapy is an increasingly attractive therapeutic approach.     

Update on the therapeutic approaches to brain tumors

Neuro-oncology is a rapidly growing field of study. The understanding of brain tumors has expanded in pace with advances in the field of molecular biology and genetics. Diagnoses are more accurate, biopsy and surgical intervention safer, radiotherapy more focused and chemotherapy safer and better tolerated. Novel strategies based on the understanding of brain tumor biology are emerging as targeted approaches to therapy. Despite all this, only a minority of patients with certain subsets of brain tumors have experienced prolonged survival. This review focuses on the standard and emerging therapies for the two most common categories of brain tumors: gliomas and meningiomas. Primary CNS lymphoma, while a relatively rare tumor, is also included as a topic of discussion as the achievements in its treatment represent the principal strides in the evolution of neuro-oncology.     

Update on the therapeutic approaches to brain tumors

Neuro-oncology is a rapidly growing field of study. The understanding of brain tumors has expanded in pace with advances in the field of molecular biology and genetics. Diagnoses are more accurate, biopsy and surgical intervention safer, radiotherapy more focused and chemotherapy safer and better tolerated. Novel strategies based on the understanding of brain tumor biology are emerging as targeted approaches to therapy. Despite all this, only a minority of patients with certain subsets of brain tumors have experienced prolonged survival. This review focuses on the standard and emerging therapies for the two most common categories of brain tumors: gliomas and meningiomas. Primary CNS lymphoma, while a relatively rare tumor, is also included as a topic of discussion as the achievements in its treatment represent the principal strides in the evolution of neuro-oncology.     

脑恶性胶质瘤放射治疗临床研究进展

脑恶性胶质瘤是成人最常见的颅内原发恶性肿瘤，其致残率和病死率均很高。术后辅助放疗是恶性胶质瘤的标准治疗手段之一，可延长患者的生存期。近年来，随着放疗技术和方法的不断发展，恶性胶质瘤的术后放疗发生了很大的变化。本文将对恶性胶质瘤的放射治疗临床研究进展进行复习。     

Recent advances in the treatment of central nervous system tumors

Introduction

Central nervous system (CNS) tumors cause a significant amount of morbidity and mortality. More research is needed to improve the prognosis of patients with CNS tumors, and especially for those with malignant gliomas. The advances over the last several years in the treatment of adult central nervous system tumors are reviewed here.

Materials and methods

Phase II and Phase III trials published in major peer-reviewed journals between 2005 and 2006 were examined. Adult central nervous system tumors including malignant glioma, low-grade glioma, primary central nervous system lymphoma, brain metastases, and neoplastic meningitis, were included.

Results

Phase II treatment trials for patients with gliomas dominated the literature in the time-period examined. Trials primarily addressed radiotherapy as well as chemotherapy in the treatment of gliomas. A number of trials examined targeted agents as single agents and in combination with systemic therapy in glioma patients. A few studies evaluated the role of chemotherapy and radiation in metastatic disease and primary CNS lymphoma.

Conclusions

Temozolomide is now the new standard of care in combination with radiation therapy for newly diagnosed glioblastomas. The optimal dosing and length of adjuvant temozolomide treatment remains unclear, and there remains no current role for neo-adjuvant therapy. Targeted agents that can be used in the salvage or front-line setting, alone or in combination with systemic therapy, will likely be the focus of future research. For metastatic brain tumors, more studies are needed to examine the exact role of radiosurgery, whole brain radiation, and the role of other therapies such as temozolomide or targeted agents. For primary CNS lymphomas, the role of various high-dose methotrexate regimens is being actively investigated.     

What is the burden of proof for tumor mutational burden in gliomas?

The treatment of patients with a variety of solid tumors has benefitted from immune checkpoint inhibition targeting the anti-programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) axis. The US Food and Drug Administration (FDA) granted accelerated approval of PD-1 inhibitor, pembrolizumab, for the treatment of adult and pediatric patients with high tumor mutational burden (TMB-H), solid tumors that have progressed following prior treatment, and who have no other treatment options, including the extension to tumors of the central nervous system (CNS). In general, pan-cancer approvals are viewed positively to empower patients and clinicians. There are subsets (eg, BRAF, NTRK) for which this pathway for approval is appropriate. However, the pan-cancer FDA approval of pembrolizumab raises several concerns regarding the generalizability of the evidence to other tumor types, including managing patients with gliomas and other CNS tumors. The cutoff for TMB-H is not well defined. There are intrinsic immunological differences between gliomas and other cancers types, including the immunosuppressive glioma microenvironment, the tumor’s effects on systemic immune function, and the transformation of the T-cell populations to an exhausted phenotype in glioma. Here, we address the caveats with pan-cancer approvals concerning gliomas and complexities of the unique CNS immune environment, discuss potential predictive biomarkers, including TMB, and explain why the recent approval should be applied with caution in CNS tumors.     

Improving outcomes for neurofibromatosis 1–associated brain tumors

Children and adults with neurofibromatosis type 1 (NF1) are predisposed to developing CNS tumors, including optic pathway gliomas (OPGs), brainstem gliomas (BSGs) and high-grade gliomas. Although current first-line treatments for low-grade gliomas (OPGs and BSGs) may prevent further tumor growth, they rarely result in restoration of the associated visual or neurological deficits. The availability of accurate small-animal models of NF1-associated brain tumors has established tractable experimental platforms for the discovery and evaluation of promising therapeutic agents. On the basis of these preclinical studies, biologically targeted agents are now being evaluated in children with NF1-associated low-grade brain tumors. Collectively, these models have also begun to reveal potential neuroprotective and risk assessment strategies for this brain tumor-prone population.