-
Journal of Clinical Oncology : Official... Jul 2011Identifying strong markers of prognosis are critical to optimize treatment and survival outcomes in patients with malignant recurrent glioma. We investigated the...
PURPOSE
Identifying strong markers of prognosis are critical to optimize treatment and survival outcomes in patients with malignant recurrent glioma. We investigated the prognostic significance of exercise behavior and functional capacity in this population.
PATIENTS AND METHODS
Using a prospective design, 243 patients with WHO grades 3 to 4 recurrent malignant glioma and Karnofsky performance status (KPS) ≥ 70 completed a self-administered questionnaire that assessed exercise behavior and performed a 6-minute walk test (6MWT) to assess functional capacity. Cox proportional models were used to estimate the risk of all-cause mortality according to 6MWT distance (6MWD; < 390 meters, 390-489 meters, > 489 meters) and exercise behavior (metabolic equivalent [MET] -h/wk) adjusted for KPS and other important clinical factors.
RESULTS
Median follow-up was 27.43 months. During this period, 149 deaths were recorded (61% of the total sample). Exercise behavior was an independent predictor of survival (P = .0081). Median survival was 13.03 months for patients reporting < 9 MET-h/wk relative to 21.84 months for those reporting ≥ 9 MET-h/wk. Exercise behavior added incremental prognostic value beyond that provided by KPS, age, sex, grade, and number of prior progressions (P < .001). Compared with patients reporting < 9 MET-h/wk, the adjusted hazard ratio for mortality was 0.64 (95% CI, 0.46 to 0.91) for patients reporting ≥ 9 MET-h/wk. Functional capacity was not an independent predictor of prognosis.
CONCLUSION
Exercise behavior is a strong independent predictor of survival that provides incremental prognostic value to KPS as well as traditional markers of prognosis in malignant recurrent glioma.
Topics: Adult; Aged; Brain Neoplasms; Exercise; Exercise Test; Female; Glioma; Health Behavior; Humans; Karnofsky Performance Status; Male; Middle Aged; Neoplasm Recurrence, Local; North Carolina; Predictive Value of Tests; Proportional Hazards Models; Prospective Studies; Risk Assessment; Risk Factors; Surveys and Questionnaires; Survival Analysis; Survival Rate; Time Factors; Treatment Outcome; Walking
PubMed: 21690470
DOI: 10.1200/JCO.2011.34.9852 -
Oncotarget May 2017Aquaporin 4 (AQP4) is the major water channel expressed in the central nervous system and is primarily expressed in astrocytes. Recently, accumulated evidence has... (Review)
Review
Aquaporin 4 (AQP4) is the major water channel expressed in the central nervous system and is primarily expressed in astrocytes. Recently, accumulated evidence has pointed to AQP4 as a key molecule that could play a critical role in glioma development. Discoveries of the role of AQP4 in cell migration suggest that AQP4 could be a significant factor regarding glioma malignancies. However, the AQP4 expression levels in glioma have not been fully elucidated; furthermore, the correlation of AQP4 expression with glioma malignancy remains controversial. Here, we review the expression pattern and predictive significance of AQP4 in malignant glioma. The molecular mechanism of AQP4 as it pertains to the migration and invasion of human glioma cells has been summarized. In addition, the important roles of AQP4 in combating drug resistance as well as potential pharmacological blockers of AQP4 have been systematically discussed. More research should be conducted to elucidate the potential roles of AQP4 in malignant glioma for identifying the tumor type, progression stages and optimal treatment strategies. The observed experimental results strongly emphasize the importance of this topic for future investigations.
Topics: Animals; Antineoplastic Agents; Aquaporin 4; Biomarkers, Tumor; Blood-Brain Barrier; Brain Neoplasms; Cell Movement; Disease Progression; Drug Resistance, Neoplasm; Gene Expression Regulation, Neoplastic; Glioma; Humans; Molecular Targeted Therapy; Neoplasm Invasiveness; Prognosis
PubMed: 28423683
DOI: 10.18632/oncotarget.16017 -
Acta Neuropathologica Dec 2012The cellular and molecular mechanisms of tumor angiogenesis and its prospects for anti-angiogenic cancer therapy are major issues in almost all current concepts of both... (Review)
Review
The cellular and molecular mechanisms of tumor angiogenesis and its prospects for anti-angiogenic cancer therapy are major issues in almost all current concepts of both cancer biology and targeted cancer therapy. Currently, (1) sprouting angiogenesis, (2) vascular co-option, (3) vascular intussusception, (4) vasculogenic mimicry, (5) bone marrow-derived vasculogenesis, (6) cancer stem-like cell-derived vasculogenesis and (7) myeloid cell-driven angiogenesis are all considered to contribute to tumor angiogenesis. Many of these processes have been described in developmental angiogenesis; however, the relative contribution and relevance of these in human brain cancer remain unclear. Preclinical tumor models support a role for sprouting angiogenesis, vascular co-option and myeloid cell-derived angiogenesis in glioma vascularization, whereas a role for the other four mechanisms remains controversial and rather enigmatic. The anti-angiogenesis drug Avastin (Bevacizumab), which targets VEGF, has become one of the most popular cancer drugs in the world. Anti-angiogenic therapy may lead to vascular normalization and as such facilitate conventional cytotoxic chemotherapy. However, preclinical and clinical studies suggest that anti-VEGF therapy using bevacizumab may also lead to a pro-migratory phenotype in therapy resistant glioblastomas and thus actively promote tumor invasion and recurrent tumor growth. This review focusses on (1) mechanisms of tumor angiogenesis in human malignant glioma that are of particular relevance for targeted therapy and (2) controversial issues in tumor angiogenesis such as cancer stem-like cell-derived vasculogenesis and bone-marrow-derived vasculogenesis.
Topics: Angiogenesis Inhibitors; Brain Neoplasms; Glioma; Humans; Neovascularization, Pathologic; Signal Transduction
PubMed: 23143192
DOI: 10.1007/s00401-012-1066-5 -
The Cochrane Database of Systematic... 2000Patients with isolated supratentorial brain tumours, presumed to be primary on imaging, have two surgical management options - biopsy or resection. Surgical opinions... (Review)
Review
BACKGROUND
Patients with isolated supratentorial brain tumours, presumed to be primary on imaging, have two surgical management options - biopsy or resection. Surgical opinions appear to be equally divided when considering the relative risks and benefits of these two procedures.
OBJECTIVES
To estimate the clinical effectiveness of radical surgical resection compared to simple biopsy in patients with malignant glioma.
SEARCH STRATEGY
Electronic database searches of COCHRANE CONTROLLED TRIALS REGISTER (including the Cochrane Cancer Network Specialised Register of Trials), MEDLINE, CANCERLIT, EMBASE, BIOSIS and SCIENCE CITATION INDEX. Hand searching the references of all identified studies; hand searching the Journal of Neuro-Oncology over the previous 10 years, including all conference abstracts; personal communication.
SELECTION CRITERIA
Randomised and clinical controlled trials were included if they compared biopsy to resection, or looked at effect of extent of resection on survival, time to progression or quality of life, for malignant glioma patients of all ages.
DATA COLLECTION AND ANALYSIS
Studies were to be identified, critically appraised and data extracted by the author (SEM). For dichotomous data, Peto odds ratios (OR) with 95% confidence intervals (CI) were hoped to have been estimated. Normal continuous data were to have been summated using the weighted mean difference (WMD).
MAIN RESULTS
The electronic database search yielded 2100 citations. Of these, two articles were identified for possible inclusion, however both were excluded. The hand search and personal communication were similarly unproductive. No studies were included in the review and no data was synthesised.
REVIEWER'S CONCLUSIONS
Given that no qualifying studies were identified and because this is an important issue, both in terms of patient risk and benefit and health economics, the author feels it important to conduct a randomised controlled trial in this subject.
Topics: Biopsy; Brain Neoplasms; Craniotomy; Glioma; Humans; Neurosurgical Procedures; Risk; Stereotaxic Techniques
PubMed: 10796847
DOI: 10.1002/14651858.CD002034 -
Indian Journal of Cancer 2009Primary malignant brain tumors account for only 2% of all adult cancers but they cause a disproportionately high cancer-related disability and death. Survival of... (Review)
Review
Primary malignant brain tumors account for only 2% of all adult cancers but they cause a disproportionately high cancer-related disability and death. Survival of malignant glioma patients has changed only modestly over the past three decades despite the emergence of new treatment strategies for these tumors. In this review, we describe the standard treatment modalities for malignant glioma, which include surgery, radiation therapy and chemotherapy, as well as the status of novel therapies that have been developed to target various aspects of glioma cell biology. We also address this issue of drug delivery as a factor limiting the efficacy of systemic administration of therapeutics and attempts to overcome this barrier. Further progress towards a cure for malignant gliomas will require a greater understanding of the underlying mechanisms driving the growth, and resistance to therapy, of these challenging tumors.
Topics: Angiogenesis Inhibitors; Antineoplastic Agents, Alkylating; Brachytherapy; Brain Neoplasms; Dacarbazine; Genetic Therapy; Glioma; Humans; Immunotherapy; Radiosurgery; Signal Transduction; Temozolomide
PubMed: 19346642
DOI: 10.4103/0019-509x.49146 -
CNS Oncology Nov 2012Lymphopenia is a common consequence of therapy for malignant glioma. Current standard therapy includes corticosteroids, temozolomide and radiation therapy, all of which... (Review)
Review
Lymphopenia is a common consequence of therapy for malignant glioma. Current standard therapy includes corticosteroids, temozolomide and radiation therapy, all of which are toxic to lymphocytes. The resulting immunosuppression has serious clinical consequences. Decreased lymphocyte counts can result in opportunistic infections, decreased efficacy of immunotherapy and reduced overall survival. The exact mechanisms underlying the association between decreased survival and lymphopenia in malignant glioma patients are unclear. However, as lymphocytes are key effector cells in the immune response to cancer, it is likely that depleting their numbers renders the immune system less effective at eliminating malignant cells. Currently, no strategies exist for the prevention or reversal of treatment-related immunosuppression in malignant glioma patients, although there are several promising theoretical approaches. This article reviews the current state of knowledge regarding the severity, etiology and possible consequences of treatment-related lymphopenia in patients with malignant glioma.
Topics: Brain Neoplasms; Clinical Trials as Topic; Glioma; Humans; Lymphocytes; Lymphopenia; Neoplasm Grading; Severity of Illness Index
PubMed: 23828734
DOI: 10.2217/cns.12.14 -
Oncotarget May 2012Because both imipramine and citalopram have been commonly used to treat depression, which commonly occurs in glioma patients, it would be interesting to conduct large...
Because both imipramine and citalopram have been commonly used to treat depression, which commonly occurs in glioma patients, it would be interesting to conduct large epidemiological studies to investigate the actual benefit that these two drugs would provide for malignant glioma patients when delivered during their glioma treatment. Such large-scale epidemiological studies have recently revealed the actual benefit provided by digoxin, a Na+/K+ ATPase inhibitor used to treat heart failure, in prostate cancer patients treated for both prostate cancer and heart failure.
Topics: Animals; Antidepressive Agents; Apoptosis; Brain Neoplasms; Cell Movement; Citalopram; Drug Resistance; Glioma; Humans; Imipramine; Molecular Targeted Therapy; Potassium Channels, Voltage-Gated
PubMed: 22695512
DOI: 10.18632/oncotarget.514 -
Cancer Immunology, Immunotherapy : CII Feb 2011Nearly twenty years of experimental immunotherapy for malignant glioma yielded important insights in the mechanisms governing glioma immunology. Still considered... (Review)
Review
Nearly twenty years of experimental immunotherapy for malignant glioma yielded important insights in the mechanisms governing glioma immunology. Still considered promising, it is clear that immunotherapy does not on its own represent the magic bullet in glioma therapy. In this review, we summarize the major immunotherapeutic achievements in the mouse GL261 glioma model, which has emerged as the gold standard syngeneic model for experimental glioma therapy. Gene therapy, monoclonal antibody treatment, cytokine therapy, cell transfer strategies and dendritic cell therapy were hereby considered. Apart from the considerable progress made in understanding glioma immunology in this model, we also addressed its most pertinent issues and shortcomings. Despite these, the GL261 model will remain indispensable in glioma research since it is a fast, highly reproducible and easy-to-establish model system.
Topics: Animals; Brain Neoplasms; Disease Models, Animal; Glioma; Immunotherapy; Mice; Neoplasms, Experimental
PubMed: 21120655
DOI: 10.1007/s00262-010-0946-6 -
Journal of Neuro-oncology Feb 2016Patients with malignant glioma who are also diagnosed with one or more primary neoplasms of other organs present a unique challenge in both determining prognosis and... (Comparative Study)
Comparative Study
Patients with malignant glioma who are also diagnosed with one or more primary neoplasms of other organs present a unique challenge in both determining prognosis and clinical management. The overlapping impact of the malignancies and their treatment result in confounding variables that may adversely affect optimal management of such patients. Additionally, the glioma-related characteristics and survival outcome of these patients is not well-defined. In this retrospective chart and data review from our longitudinal database, we identified patients with malignant glioma including anaplastic glioma and glioblastoma, diagnosed between January 2005 and June 2011, who were also diagnosed with other non-CNS primary neoplasms. Patients with known genetic syndromes were excluded. The data was analyzed to determine the clinical characteristics and glioma-related survival. A total of 204 patients with malignant glioma (165 glioblastoma and 39 anaplastic glioma) were identified. There was no significant difference in the overall survival or progression-free survival between patients with malignant glioma plus non-CNS primary neoplasm when compared with patients with malignant glioma only. In patients with glioblastoma and non-CNS malignancy, the duration between diagnosis of glioblastoma and non-CNS neoplasms did not significantly alter glioma-related survival. Patients with malignant glioma who were diagnosed with other non-CNS malignancy have survival outcome comparable to those with malignant glioma only. The duration between diagnosis of glioblastoma and diagnosis of non-CNS neoplasms did not affect survival. Further prospective studies specifically addressing survival and molecular characteristics of patients with malignant glioma plus non-CNS cancers are recommended.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Brain Neoplasms; Case-Control Studies; Female; Follow-Up Studies; Glioma; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Neoplasms, Multiple Primary; Prognosis; Retrospective Studies; Survival Rate; Young Adult
PubMed: 26566652
DOI: 10.1007/s11060-015-1992-x -
Expert Opinion on Pharmacotherapy Oct 2014Malignant gliomas (MGs) represent the most common primary brain tumors in adults, the most deadly of which is grade IV glioblastoma. Patients with glioblastoma... (Review)
Review
INTRODUCTION
Malignant gliomas (MGs) represent the most common primary brain tumors in adults, the most deadly of which is grade IV glioblastoma. Patients with glioblastoma undergoing current standard-of-care therapy have a median survival of 12 - 15 months.
AREAS COVERED
Over the past 25 years, there have been modest advancements in the treatment of MGs. Assessment of therapeutic responses has continued to evolve to account for the increasing number of agents being tested in the clinic. Currently approved therapies for primary tumors have been extended for use in the setting of recurrent disease with modest efficacy. Agents initially approved for recurrent gliomas have begun to demonstrate efficacy against de novo tumors but will ultimately need to be evaluated in future studies for scheduling, timing and dosing relative to chemotherapy.
EXPERT OPINION
Screening and identification of tumor-specific mutations is critical for the advancement of effective therapy that is both safe and precise for the patient. Two unique antigens found in glioblastoma are currently being employed as targets for immunotherapeutic vaccines, one of which has advanced to Phase III testing. Whole genome sequencing of MGs has yielded two other novel mutations that offer great promise for the development of molecular inhibitors.
Topics: Angiogenesis Inhibitors; Antigens, Neoplasm; Antineoplastic Agents; Biomarkers, Tumor; Brain Neoplasms; Cancer Vaccines; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Combined Modality Therapy; Glioblastoma; Glioma; Humans; Mutation; Neoplasm Recurrence, Local; Standard of Care
PubMed: 25139628
DOI: 10.1517/14656566.2014.947266