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Nature Reviews. Clinical Oncology May 2012Gliomas in children differ from their adult counterparts by their distribution of histological grade, site of presentation and rate of malignant transformation. Although... (Review)
Review
Gliomas in children differ from their adult counterparts by their distribution of histological grade, site of presentation and rate of malignant transformation. Although rare in the paediatric population, patients with high-grade gliomas have, for the most part, a comparably dismal clinical outcome to older patients with morphologically similar lesions. Molecular profiling data have begun to reveal the major genetic alterations underpinning these malignant tumours in children. Indeed, the accumulation of large datasets on adult high-grade glioma has revealed key biological differences between the adult and paediatric disease. Furthermore, subclassifications within the childhood age group can be made depending on age at diagnosis and tumour site. However, challenges remain on how to reconcile clinical data from adult patients to tailor novel treatment strategies specifically for paediatric patients.
Topics: Adult; Age Factors; Brain Neoplasms; Child; Glioma; Humans; Prognosis
PubMed: 22641364
DOI: 10.1038/nrclinonc.2012.87 -
Strahlentherapie Und Onkologie : Organ... Apr 2003Standard treatment in patients with malignant glioma consists of surgery and postoperative radiotherapy. A high early recurrence rate, particularly in glioblastoma, has... (Comparative Study)
Comparative Study Review
BACKGROUND
Standard treatment in patients with malignant glioma consists of surgery and postoperative radiotherapy. A high early recurrence rate, particularly in glioblastoma, has led to the investigation of additional chemotherapy.
MATERIAL AND METHODS
Recent results of radiochemotherapy published in the literature were reviewed with respect to outcome in phase II and III trials. Based on these experiences, aspects of future strategies were discussed.
RESULTS
3 decades of intensive research had, unfortunately, little impact on the overall results. While early prospective studies established adjuvant nitrosoureas, particularly BCNU, as suitable adjuvant to surgery and postoperative radiotherapy, further studies largely concentrated on combined chemotherapeutic protocols, mostly procarbazine, CCNU and vincristine (PCV), which was shown to prolong survival in anaplastic astrocytoma. The recent MRC study, however, showed no effect for adjuvant PCV in grade III and IV malignant glioma. Only in high-grade glioma with an oligodendroglial component, additional chemotherapy may be of a decisive benefit. The introduction of newer drugs such as paclitaxel, temozolomide, or gemcitabine demonstrated no decisive advantage. Different modes of application and sequencing of radiotherapy and chemotherapy are presently actively investigated, but failed to substantially improve outcome.
CONCLUSIONS
Therefore, search for newer and more effective drugs continues, as well as for "optimal" administration and sequencing, especially from the standpoint of accompanying acute and late toxicity. Finally, recent endeavors focused on basic research such as angiogenesis, migration and invasion, or induction of cell differentiation, but these strategies are still away from broader clinical investigation.
Topics: Adult; Age Factors; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Astrocytoma; Brain Neoplasms; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Combined Modality Therapy; Double-Blind Method; Genetic Therapy; Glioblastoma; Glioma; Humans; Meta-Analysis as Topic; Neoadjuvant Therapy; Oligodendroglioma; Prospective Studies; Quality of Life; Radiotherapy Dosage; Randomized Controlled Trials as Topic; Research; Stem Cell Transplantation; Time Factors; Treatment Outcome
PubMed: 12707711
DOI: 10.1007/s00066-003-1027-y -
Journal of Neurovirology Apr 1998The goals of surgery for malignant glioma are to establish a histological diagnosis and to achieve mechanical cytoreduction to reduce intracranial pressure (ICP) and... (Review)
Review
The goals of surgery for malignant glioma are to establish a histological diagnosis and to achieve mechanical cytoreduction to reduce intracranial pressure (ICP) and possibly alter tumor kinetics. There is controversy concerning the question whether the glioma is a focal or diffuse process; it appears that there may be variability between the two extremes in individual cases. The question of the value of surgery has also been controversial. Review of the literature suggests that both early and long-term postoperative outcome after radical surgical resection are better than the results of either partial resection or simple biopsy, in terms of neurological status and duration of survival. Similarly, reoperation for recurrence of glioma offers reasonable extension of quality survival. Despite the desirability of extensive cytoreductive surgery for malignant gliomas, the presence of viable infiltrative cells beyond the margins of the resection necessitate that surgery be a part of an aggressive multimodality therapeutic approach. Adjunctive measures to control the infiltrative component include newer forms of radiotherapy (such as stereotaxic radiosurgery) and newer delivery techniques for chemotherapy (agents impregnated in biodegradable polymers implanted in the tumor bed after surgical resection), and possibly immunotherapy and gene therapy as they may become feasible in the future. The strategy for management of malignant glioma thus consists of a combination of extensive surgical resection to reduce the accessible tumor burden, followed in rapid sequence by measures to control the infiltrative portion of the tumor. It is recommended that these measures be offered 'up front' rather than delaying treatment until there is clinical or radiographic evidence of tumor recurrence.
Topics: Adult; Aged; Brain Neoplasms; Combined Modality Therapy; Female; Glioma; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Treatment Outcome
PubMed: 9584959
DOI: 10.3109/13550289809114522 -
Pharmacological Research Jun 2020Despite many endeavors to treat malignant gliomas in the last decades, the median survival of patients has not significantly improved. The infiltrative nature of... (Review)
Review
Despite many endeavors to treat malignant gliomas in the last decades, the median survival of patients has not significantly improved. The infiltrative nature of high-grade gliomas and the impermeability of the blood-brain barrier to the most therapeutic agents remain major hurdles, impeding an efficacious treatment. Theranostic platforms bridging diagnosis and therapeutic modalities aim to surmount the current limitations in diagnosis and therapy of glioma. Gold nanoparticles (AuNPs) due to their biocompatibility and tunable optical properties have widely been utilized for an assortment of theranostic purposes. In this Review, applications of AuNPs as imaging probes, drug/gene delivery systems, radiosensitizers, photothermal transducers, and multimodal theranostic agents in malignant gliomas are discussed. This Review also aims to provide a perspective on cancer theranostic applications of AuNPs in future clinical trials.
Topics: Animals; Antineoplastic Agents; Brain Neoplasms; Drug Carriers; Gene Transfer Techniques; Genetic Therapy; Glioma; Gold Compounds; Humans; Immunotherapy; Metal Nanoparticles; Molecular Imaging; Photochemotherapy; Photothermal Therapy; Predictive Value of Tests; Theranostic Nanomedicine
PubMed: 32209363
DOI: 10.1016/j.phrs.2020.104753 -
Neuro-oncology Mar 2018The use of contrast enhancement within the brain on CT or MRI has been the gold standard for diagnosis and therapeutic response assessment in malignant gliomas for... (Review)
Review
The use of contrast enhancement within the brain on CT or MRI has been the gold standard for diagnosis and therapeutic response assessment in malignant gliomas for decades. The use of contrast enhancing tumor size, however, remains controversial as a tool for accurately diagnosing and assessing treatment efficacy in malignant gliomas, particularly in the current, quickly evolving therapeutic landscape. The current article consolidates overwhelming evidence from hundreds of studies in the field of neuro-oncology, providing the necessary evidence base and specific contexts of use for consideration of contrast enhancing tumor size as an appropriate surrogate biomarker for disease burden and as a tool for measuring treatment response in malignant glioma, including glioblastoma.
Topics: Biomarkers; Brain Neoplasms; Contrast Media; Evidence-Based Medicine; Glioma; Humans; Neuroimaging
PubMed: 29040703
DOI: 10.1093/neuonc/nox193 -
Expert Review of Neurotherapeutics Nov 2005Malignant gliomas comprise a small percentage of all cancers, but continue to cause disproportionate levels of morbidity and mortality. Despite decades of intensive... (Review)
Review
Malignant gliomas comprise a small percentage of all cancers, but continue to cause disproportionate levels of morbidity and mortality. Despite decades of intensive effort from many disciplines--surgery, radiation oncology and medicine--they remain refractory to cure and, in most cases, even to prolonged treatment response. Comprehensive multidisciplinary treatment is well recognized as the optimal approach. While continued advances and refinement in both surgical and radiotherapy-based techniques are certain, medical therapies are expanding at a much more rapid rate. This is due, in large part, to an understanding of the molecular events that underlie cancer pathogenesis and improved laboratory techniques to manufacture and study molecules that influence this process. This review will focus on medical therapies in the treatment of malignant glioma, never losing sight of their place as one of several therapeutic modalities used to confront brain cancer.
Topics: Antineoplastic Agents; Drug Therapy; Enzyme Inhibitors; Expert Testimony; Glioma; Humans
PubMed: 16274270
DOI: 10.1586/14737175.5.6.S41 -
Expert Opinion on Emerging Drugs Mar 2008Malignant gliomas are amongst the most devastating and intractable of all cancers. The most common malignant glioma, glioblastoma multiforme (GBM), is associated with a... (Review)
Review
BACKGROUND
Malignant gliomas are amongst the most devastating and intractable of all cancers. The most common malignant glioma, glioblastoma multiforme (GBM), is associated with a median survival in the range of 12-15 months. Survival for patients with GBM has improved with the addition of temozolomide chemotherapy to post-operative radiotherapy. Further advances in the treatment of malignant glioma will hinge on the discovery of novel and likely targeted therapies with activity against these diseases.
OBJECTIVE
Review recent published experience using targeted therapeutics for malignant glioma.
METHODS
Key studies from a Medline review of targeted therapies for malignant glioma performed between 2000 and the present are summarised in this review.
CONCLUSIONS
Experience with targeted therapeutics for malignant glioma has been to date disappointing. These agents are generally well tolerated, but activity is limited. Novel therapeutics with activity against malignant gliomas must be identified to improve prognosis for patients with these diseases.
Topics: Animals; Antineoplastic Agents; Brain Neoplasms; Drugs, Investigational; Glioma; Humans
PubMed: 18321150
DOI: 10.1517/14728214.13.1.81 -
Swiss Medical Weekly 2011Glioblastomas (World Health Organisation (WHO) grade IV) and anaplastic gliomas (astrocytomas, oligoastrocytomas, oligodendrogliomas) (WHO grade III) are collectively... (Review)
Review
Glioblastomas (World Health Organisation (WHO) grade IV) and anaplastic gliomas (astrocytomas, oligoastrocytomas, oligodendrogliomas) (WHO grade III) are collectively referred to as malignant gliomas. The diagnosis of malignant glioma may be suspected based on clinical history and neuroimaging findings, but histological confirmation remains the diagnostic "gold standard". Molecular markers such as 1p/19q codeletion and isocitrate dehydrogenase (IDH) mutation provide important diagnostic and prognostic information. O-methylguanylmethyltransferase (MGMT) promoter methylation is another favourable prognostic marker and predicts benefit from alkylating agent chemotherapy in glioblastoma. Additionally, the extent of neurosurgical resection is a prognostic factor. Radiotherapy of the involved brain region or chemotherapy using the alkylating agent, temozolomide, are common therapeutic options for patients with anaplastic glioma. In contrast, temozolomide plus radiotherapy is the standard of care for most patients with glioblastoma. The increasing population of elderly patients with glioblastoma represents a particular challenge, with surgery followed by radiotherapy as the standard of care. Contemporary clinical studies focus on the role of angiogenesis. Specifically, pivotal phase III studies exploring the antibody to vascular endothelial growth factor (VEGF), bevacizumab, and the αvβ3/5 antagonist, cilengitide, in the management of newly diagnosed glioblastoma have completed enrolment. Moreover, a broad spectrum of other experimental treatment approaches, including immunotherapy with vaccines against glioma-associated antigens, are currently being explored in phase I/II clinical trials.
Topics: Biomarkers, Tumor; Central Nervous System Neoplasms; Glioblastoma; Humans; Neoplasm Recurrence, Local; Oligodendroglioma
PubMed: 21607882
DOI: 10.4414/smw.2011.13210 -
Topics in Magnetic Resonance Imaging :... Apr 2020Malignant gliomas constitute a smaller portion of brain tumors in children compared with adults. Nevertheless, they can be devastating tumors with poor prognosis. Recent... (Review)
Review
Malignant gliomas constitute a smaller portion of brain tumors in children compared with adults. Nevertheless, they can be devastating tumors with poor prognosis. Recent advances and improved understanding of the genetic and molecular characterization of pediatric brain tumors, including those of malignant gliomas, have led to the reclassification of many pediatric brain tumors and new entities have been defined. In this paper, we will present some of the more recent characterization and pertinent changes in pediatric high-grade gliomas, along with the conventional and advanced imaging features associated with these entities. Implications of the recent changes in pediatric malignant glioma classifications will also be discussed.
Topics: Adult; Brain; Brain Neoplasms; Child; Glioma; Humans; Magnetic Resonance Imaging; Pediatrics
PubMed: 32271285
DOI: 10.1097/RMR.0000000000000235 -
Cellular and Molecular Life Sciences :... Oct 1999Despite the considerable progress in modern tumor therapy, the prognosis for patients with glioblastoma, the most frequent malignant brain tumor, has not been... (Review)
Review
Despite the considerable progress in modern tumor therapy, the prognosis for patients with glioblastoma, the most frequent malignant brain tumor, has not been substantially improved. Although cytoreductive surgery and radiotherapy are the mainstays of treatment for malignant glioma at present, novel cytotoxic drugs and immunotherapeutic approaches hold great promise as effective weapons against these malignancies. Thus, great efforts are being made to enhance antitumoral efficacy by combining various cytotoxic agents, by novel routes of drug administration, or by combining anticancer drugs and immune modulators. Immunotherapeutic approaches include cytotoxic cytokines, targeted antibodies, and vaccination strategies. However, the success of most of these experimental therapies is prevented by the marked molecular resistance of glioma cells to diverse cytotoxic agents or by glioma-associated immunosuppression. One promising experimental strategy to target glioma is the employment of death ligands such as CD95 (Fas/Apo1) ligand or Apo2 ligand (TRAIL). Specific proapoptotic approaches may overcome many of the obvious obstacles to a satisfactory management of malignant brain tumors.
Topics: Animals; Antigen Presentation; Antigens, Neoplasm; Apoptosis; Apoptosis Regulatory Proteins; Blood-Brain Barrier; Clinical Trials as Topic; Cytokines; Drug Therapy; Fas Ligand Protein; Glioma; Humans; Immunosuppression Therapy; Immunotherapy; Ligands; Membrane Glycoproteins; Radiotherapy; TNF-Related Apoptosis-Inducing Ligand; Treatment Failure; Tumor Necrosis Factor-alpha; Vaccination
PubMed: 11212300
DOI: 10.1007/s000180050447