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Table of contents
- Journal of Clinical Oncology
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The most extensively evaluated has been the vascular endothelial growth factor VEGF neutralizing antibody bevacizumab Avastin.
Journal of Clinical Oncology
The biological phenomenon of tumor-associated blood vessel proliferation angiogenesis is recognized as a significant sequela of high intratumoral VEGF production, a suspected driver of gliomagenesis and definite contributor to neurological dysfunction due to blood—brain barrier dysfunction and associated cerebral edema. Unfortunately, adding bevacizumab to standard radiation and temozolomide for newly diagnosed glioblastoma yielded no survival advantage in two randomized, controlled, and blinded clinical trials [ 5 , 6 ].
Subset analysis and clinical experience suggests the existence of patient subsets that may benefit from VEGF-targeted therapy and continued efforts to identify these and understand the molecular driving events are ongoing. Currently, the benefit of bevacizumab is limited to patients with recurrent malignant glioma based on improved quality of life and prolonged progression-free survival as evaluated by magnetic resonance imaging MRI [ 7 ].
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The significance of these radiographic and clinical responses to bevacizumab remains controversial as bevacizumab has the potential to normalize the disrupted tumor-associated blood—brain barrier, reduce cerebral edema, and thereby improve symptoms in the absence of a true antitumor effect i. Pseudo-response and pseudo-progression, the well-documented worsening of MRI in response to treatment-induced blood—brain barrier disruption in the absence of true tumor progression, are major obstacles to clinical decision making within and outside of clinical trial therapy.
Improving the specificity of MRI, positron emission spectroscopy, and other nonsurgical diagnostics is critical to the future of clinical neuro-oncology that is so highly dependent upon image-based decision making. Progress in treating glioblastoma, the most common and aggressive malignant brain tumor, is being made but too slowly and too incrementally. There remains continued frustration over the pace at which substantive developments have translated to improving patient survival.
In contrast to this is the excitement and promise stemming from the fact that the most common adult and pediatric malignant brain tumors now represent some of the most extensively studied cancers at the molecular, genetic, and epigenetic levels, owing, in great part, to the NCI-funded Cancer Genome Atlas Project initiated in and comparably modeled collaborative efforts in medulloblastoma and other less common tumor types [ 8 ].
SISTEMA DE BIBLIOTECAS EPN - catalog › Details for: Emerging Concepts in Neuro-Oncology
This has led to a deeper understanding of the molecular basis of brain cancer heterogeneity and a foundation for more advanced evidenced-based clinical decision making and personalized targeted therapeutics. Positive developments include how medulloblastoma molecular subtyping has started to impact treatment regimens, and the potential therapeutic efficacy of BRAF inhibitor therapy in BRAFVE mutated brain tumors [ 9 ].
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These significant advances in defining the molecular underpinnings of CNS cancers and the contributions these events make to the disease biology, as well as the ability to subclassify malignancies based on genomics are leading to improved therapeutic recommendations. The current environment of translating molecular and biological discoveries into meaningful advances for patients is dependent upon early-phase clinical trials, which emphasize defining and identifying specific targets and quantifying target effects within tumor tissue.
The integration of biological endpoints into clinical development remains challenging. Numerous factors from the identification of eligible patients, involvement of multiple clinical and scientific disciplines, and assay development create a bottleneck to the timely translation of laboratory findings to patients.
Solutions involve multidisciplinary research teams, engagement and participation of laboratory scientists in clinical research, and advanced understanding of targets in the tumor microenvironment. Despite major setbacks in large randomized clinical trials, the future for patients with CNS cancers is improving.
As can be seen in this issue of Neurotherapeutics , advances are occurring across disciplines. Among the most exciting and of immediate clinical utility include the subclassification of glioma and medulloblastoma with incorporation of the new World Health Organization guidelines. This progress is reviewed and discussed by Howard Colman and Scott Pomeroy.
David Eisenstat addresses epigenetic pathways in pediatric high-grade glioma with an emphasis on their role in disease progression and potential as therapeutic targets.
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Building upon these molecular insights, Stephen Dombrowski and David James explore the unique nature of brain cancer stem cells, and the utility and role of contemporary animal models for preclinical therapeutic testing. Therefore, although rare cases lacking a clear distinction may be encountered, the term LGG should be abandoned for a more specific diagnosis whenever possible. The primary goals of this paper are to review practical surgical pathology issues related to the diagnosis of diffuse LGGs and to update the reader on emerging clinicopathologic and molecular genetic concepts.
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Close mobile search navigation Article navigation. Pathology of low-grade gliomas: An update of emerging concepts Arie Perry. Abstract Although the term low-grade glioma LGG is useful for its connotation of a slow-growing, better prognosis CNS primary neoplasm typically occurring in a young patient, it also serves as a potential diagnostic wastebasket, occasionally leading to conceptual errors, therapeutic uncertainty, or misinterpretation of clinical data.
Managing the Elderly Patient -- Neuro-oncology is one of the most exciting and rapidly evolving areas of oncology.
In recent years there has been a remarkable increase in activity in the field, from basic science through to the clinic. This is reflected by advances in the understanding of the biology of CNS malignancies which have informed the development of novel and successful therapies.
In this environment it is essential to facilitate communication and understanding of new ideas and concepts. Emerging Concepts in Neuro-Oncology is written with this in mind: The book moves from concepts in the scientific basis of neuro-oncology in part one, through models of brain cancer in part two, to emerging concepts in clinical practice in part three, with a focus on translational research. This book will be an essential read for neuroscience researchers, cancer researchers, neurosurgeons and clinical oncologists as well as anyone with an interest in this exciting, dynamic field.