New treatment strategies for malignant gliomas

Malignant gliomas are the most prevalent type of primary brain tumor in adults. Despite progress in brain tumor therapy, the prognosis of malignant glioma patients remains dismal. The median survival of patients with glioblastoma multiforme, the most common grade of malignant glioma, is 10-12 months. Conventional therapy of surgery, radiation and chemotherapy is largely palliative. Essentially, tumor recurrence is inevitable. Salvage treatments upon recurrence are palliative at best and rarely provide significant survival benefit. Therapies targeting the underlying molecular pathogenesis of brain tumors are urgently required. Common genetic abnormalities in malignant glioma specimens are associated with aberrant activation or suppression of cellular signal transduction pathways and resistance to radiation and chemotherapy. Several low molecular weight signal transduction inhibitors have been examined in preclinical and clinical malignant glioma trials. The efficacy of these agents as monotherapies has been modest, at best; however, small subsets of patients who harbor specific genetic changes in their tumors may display favorable clinical responses to defined small molecule inhibitors. Multitargeted kinase inhibitors or combinations of agents targeting different mitogenic pathways may overcome the resistance of tumors to single-agent targeted therapies. Well designed studies of small molecule kinase inhibitors will include assessment of safety, drug delivery, target inhibition and correlative biomarkers to define mechanisms of response or resistance to these agents. Predictive biomarkers will enrich for patients most likely to respond in future clinical trials. Additional clinical studies will combine novel targeted therapies with radiation, chemotherapies and immunotherapies.     

New treatment strategies for malignant gliomas

Malignant gliomas are the most prevalent type of primary brain tumor in adults. Despite progress in brain tumor therapy, the prognosis of malignant glioma patients remains dismal. The median survival of patients with glioblastoma multiforme, the most common grade of malignant glioma, is 10–12 months. Conventional therapy of surgery, radiation and chemotherapy is largely palliative. Essentially, tumor recurrence is inevitable. Salvage treatments upon recurrence are palliative at best and rarely provide significant survival benefit. Therapies targeting the underlying molecular pathogenesis of brain tumors are urgently required. Common genetic abnormalities in malignant glioma specimens are associated with aberrant activation or suppression of cellular signal transduction pathways and resistance to radiation and chemotherapy. Several low molecular weight signal transduction inhibitors have been examined in preclinical and clinical malignant glioma trials. The efficacy of these agents as monotherapies has been modest, at best; however, small subsets of patients who harbor specific genetic changes in their tumors may display favorable clinical responses to defined small molecule inhibitors. Multitargeted kinase inhibitors or combinations of agents targeting different mitogenic pathways may overcome the resistance of tumors to single-agent targeted therapies. Well designed studies of small molecule kinase inhibitors will include assessment of safety, drug delivery, target inhibition and correlative biomarkers to define mechanisms of response or resistance to these agents. Predictive biomarkers will enrich for patients most likely to respond in future clinical trials. Additional clinical studies will combine novel targeted therapies with radiation, chemotherapies and immunotherapies.     

New chemotherapy options for the treatment of malignant gliomas.

Chemotherapy remains part of the treatment triad that includes surgery and radiation therapy for the management of malignant gliomas. In recent years there has been an increased understanding of the molecular pathways of malignant transformation. Based on this research, new drugs have been evaluated, with specific cellular targets in mind that can be modified or inhibited. Many of these agents are now being tested in phase I and II clinical trials and have shown some promising results. Clearly, not all patients with malignant gliomas respond equally to chemotherapy. Recent evidence suggests that certain molecular markers may predict chemosensitivity in some tumor types, particularly anaplastic oligodendroglioma. This article reviews recent trends in the use of chemotherapy and clinical trials of new therapies for adults with malignant gliomas.     

恶性胶质瘤的综合治疗现状

恶性胶质瘤是常见的肿瘤,其死亡率和致残率均很高,手术、放疗及化疗的综合治疗已经成为恶性胶质瘤治疗常规。近年来,术后放疗及化疗出现了许多进展。本文就恶性胶质瘤的综合治疗现状及进展作一综述。     

Intra-arterial cisplatin for the treatment of malignant gliomas

Summary Cisplatin (DDP) is a chemotherapeutic agent that has shown efficacy against primary CNS malignancies. Intraarterial (IA) administration of DDP to patients with brain tumors should produce higher peak levels of drug than intravenous (IV) administration of an identical dose and reduce systemic toxicity. Twelve patients with malignant glioma were entered into the study. All had failed irradiation, 11 had failed IA BCNU. Each patient received IA DDP, 58–100 mg/m², into the internal carotid artery at four to six week intervals. One of 12 patients had a partial response of 6 months. The remaining 11 patients had progressive disease [10] or severe complications [1]. Toxicity included seizures in four patients, weakness and/or aphasia in four patients, coma in two patients, and visual deterioration in two patients. IA DDP has very limited efficacy in patients with malignant gliomas after failure of nitrosoureas and is associated with an unacceptable level of toxicity. IA DDP may be more effective when used as initial chemotherapy of malignant gliomas.     

The basis for current treatment recommendations for malignant gliomas

Although primary brain tumors represent an important cause of cancer related mortality in the United States, advances in the treatment of these tumors has been slow and has generally lagged behind that of most systemic tumors. One of the major reasons for this is the paucity of well conducted, prospective radiation and chemotherapy trials. For the brain tumor trials that have been conducted, small patient numbers, heterogeneous patient populations, and non-uniformity of response criteria, have made the current clinical data base difficult to interpret. Data from several prospective, multi-institutional randomized trials have defined a role for radiation therapy in the treatment of malignant gliomas and on-going trials will help define refinements in technique. Although there does appear to be a place for the use of chemotherapy in the treatment of a subgroup of patients with malignant gliomas, its role for the majority of patients remains unclear. Only through better understanding of the biology of these tumors, more effective therapies, and the implementation of better clinical trial design can we hope to make significant progress in the treatment of malignant gliomas.     

A comparison of treatment results for recurrent malignant gliomas

Retreatment of malignant gliomas may be performed with palliative intent after careful consideration of the risks and benefits, and with special regards to iatrogenic neurotoxicity and quality of life (QOL). This review compares studies of several retreatment strategies (published between 1987 and 2000) based on the quality of their evidence. Depending on both established prognostic factors and previous treatment, individually tailored retreatment strategies are possible. In all studies that included a multivariate analysis of prognostic factors, performance status was the most important. So far, predictive factors for response, which might facilitate patient selection, have not been unequivocally defined.In terms of QOL, single-agent chemotherapy (temozolomide, nitrosoureas, platinum and taxane derivatives) may offer a better therapeutic ratio than polychemotherapy. For glioblastoma multiforme, progression-free survival and QOL were more favourable after temozolomide than procarbazine (level 1 evidence).The survival of patients after various radiotherapy techniques is broadly similar. However, considerable toxicity is associated with radiosurgery or brachytherapy. Fractionated stereotactic radiotherapy plus radio-sensitizing cytostatic agents has shown promising initial results in small groups of selected patients and awaits further evaluation. Level 2 evidence derived from non-randomized studies does not suggest a substantial prolongation of survival by re-resection as compared with chemotherapy or radiotherapy alone. Level 1 evidence derived from a randomized trial suggests that application of BCNU polymers significantly improves the outcome after re-resection. However, most studies reported median survival in the range of only 25-35 weeks, thereby emphasizing the need for the development and clinical evaluation of new innovative treatment approaches.     

New developments in surgery of malignant gliomas

BACKGROUND: Malignant gliomas account for a high proportion of brain tumours. With new advances in neurooncology, the recurrence-free survival of patients with malignant gliomas has been substantially prolonged. It, however, remains dependent on the thoroughness of the surgical resection. The maximal tumour resection without additional postoperative deficit is the goal of surgery on patients with malignant gliomas. In order to minimize postoperative deficit, several pre- and intraoperative techniques have been developed. CONCLUSIONS: Several techniques used in malignant glioma surgery have been developed, including microsurgery, neuroendoscopy, stereotactic biopsy and brachytherapy. Imaging and functional techniques allowing for safer tumour resection have a special value. Imaging techniques allow for better preoperative visualization and choice of the approach, while functional techniques help us locate eloquent regions of the brain.     

Chemotherapy in the treatment of malignant gliomas

Malignant gliomas are one of the most difficult tumors to treat, with only modest advances being made in the past few decades. Surgery and radiation have had the greatest impact, increasing survival. Chemotherapy modestly increases survival. The use of chemotherapy in the treatment of malignant gliomas is the focus of this paper and the more commonly used agents at diagnosis and relapse are reviewed. Since most patients fail first-, second- and even third-line agents that are commercially available, some of the more relevant new biological compounds will also be discussed. As treatments for brain tumors evolve, it is likely that optimal therapies will come from combination therapies that incorporate target-specific and chemotherapeutic agents.     

Chemotherapy in the treatment of malignant gliomas

Malignant gliomas are one of the most difficult tumors to treat, with only modest advances being made in the past few decades. Surgery and radiation have had the greatest impact, increasing survival. Chemotherapy modestly increases survival. The use of chemotherapy in the treatment of malignant gliomas is the focus of this paper and the more commonly used agents at diagnosis and relapse are reviewed. Since most patients fail first-, second- and even third-line agents that are commercially available, some of the more relevant new biological compounds will also be discussed. As treatments for brain tumors evolve, it is likely that optimal therapies will come from combination therapies that incorporate target-specific and chemotherapeutic agents.     

Chemosensitivity assays for malignant gliomas

Chemosensitivity assays including colony forming assay (CFA), MTT dye reduction assay (MTT assay) and thymidine incorporation assay (TIA) for cultured rat and human glioma cells were conducted to determine the correlation among them and the in vivo antitumor efficacy of anticancer drugs using rats implanted glioma cells. Cytotoxicity of various agents such as ACNU, ACR, CDDP, VCR or BLM, was estimated from the concentrations which caused 50% inhibition of the cell growth at the peak plasma concentration. The survival time of tumor bearing rats was assessed after ip treatment with these agents at their estimated clinical doses. This parameter was greater in the drugs that were shown to be highly sensitive in CFA and was consistent with the data for CFA. In the chemosensitivity assays, CFA closely correlated to MTT assay for all agents except VCR, but poorly so to TIA. The results in this study indicate that MTT assay seemed to be useful for determining the chemosensitivity of anticancer drugs and that chemosensitivity assay should be conducted depending on the nature of anticancer drug.     

Blood-based biomarkers for malignant gliomas

Malignant gliomas remain incurable and present unique challenges to clinicians, radiologists and clinical and translational investigators. One of the major problems in treatment of these tumors is our limited ability to reliably assess tumor response or progression. The most frequently used neuro-imaging studies (contrast-enhanced MRI and CT) rely on changes of blood–brain barrier (BBB) integrity, providing only an indirect assessment of tumor burden. In addition, the BBB can be altered by commonly used interventions including radiation, glucocorticoids and vascular endothelial growth factor inhibitors, further complicating the interpretation of scans. Newer radiologic techniques including PET and magnetic resonance spectroscopy are theoretically promising but thus far have not meaningfully changed the assessment of patients with malignant gliomas. A tumor-specific, blood-based biomarker would be of immediate use to clinicians and investigators if sufficiently sensitive and specific. This review discusses the potential utility of such a biomarker, the general classes of tumor-derived blood-based biomarkers and it summarizes the currently available data on circulating tumor cells, circulating nucleic acids and circulating proteins in patients with malignant gliomas. It is unclear which marker or marker class appears to be the most promising for these tumors. This article provides thoughts on how novel candidate blood-based markers could be discovered and tested in a more comprehensive way and why these efforts should be among the top priorities in neuro-oncologic research in the coming years.     

Changing boundaries in the treatment of malignant gliomas

Malignant gliomas are still among the most lethal and difficult tumors to treat; even the most intensive combinations of radio- and chemotherapy are not curative and yield only a modest impact on survival for most of these patients, as long-term survivors are less than 10%. There is a major need for new chemotherapeutic drugs and alternative therapeutic modalities. This review aims to define the best standard treatment in the common clinical practice and also summarizes the most promising lines of investigational research in the field of neuro-oncology, which will probably offer new and long-awaited valid therapy options for brain tumor patients.     

Changing boundaries in the treatment of malignant gliomas

Malignant gliomas are still among the most lethal and difficult tumors to treat; even the most intensive combinations of radio- and chemotherapy are not curative and yield only a modest impact on survival for most of these patients, as long-term survivors are less than 10%. There is a major need for new chemotherapeutic drugs and alternative therapeutic modalities. This review aims to define the best standard treatment in the common clinical practice and also summarizes the most promising lines of investigational research in the field of neuro-oncology, which will probably offer new and long-awaited valid therapy options for brain tumor patients.     

New strategies for the management of malignant ascites

Intractable malignant ascites accounts for 6% of all hospice admissions. The onset of malignant ascites indicates a poor prognosis, hence minimal supportive therapy is indicated. This paper examines the method of control for malignant ascites presently available to patients, examines their limitations and proposes new strategies for managing intractable malignant ascites. Ascites is discussed in terms of its pathology—that is, as a form of lymphoedema. With this in mind treatment is proposed based upon principles incorporated into lymphoedema management. Nurses have taken a dominant role in the care of patients with lymphoedema and there appears no reason why ascites management cannot become the remit of nurses offering appropriate, but predominantly palliative therapy.     

替莫唑胺优化方案在恶性胶质瘤治疗中的应用

恶性胶质瘤为颅内常见恶性肿瘤，病程进展快，病死率高，为神经外科的治疗难点。替莫唑胺抗恶性胶质瘤效果确切，有必要探索优化治疗方案进一步提高疗效。各种替莫唑胺优化方案在恶性胶质瘤的初步治疗中已获得肯定疗效，但仍需多中心随机双盲临床试验和基础实验进一步证实。     

A review of management strategies of malignant gliomas in the elderly population

Glioblastoma Multiforme (GBM) is the most frequent primary malignant brain tumor in adults. It is an aggressive primary brain neoplasm, associated with a poor prognosis and median survival of less than 1 year. Approximately 50% of patients diagnosed with malignant gliomas in the United States are over the age of 65. Advancing age and poor performance status are two variables that have found to negatively affect prognosis. When compared to younger patients, not only is the treatment of elderly patients associated with decreased efficacy but also greater toxicity. As a result, elderly patients often receive less aggressive treatment and are excluded from clinical trials. There are many challenges in the treatment of elderly patients with GBM including increased surgical morbidity and mortality as well as increased toxicity to radiation and chemotherapy. As such, the optimal therapy remains unclear and controversial for the elderly malignant glioma population.