-
Advances in Experimental Medicine and... 2023This chapter provides a comprehensive overview of malignant gliomas, the most common primary brain tumor in adults. These tumors are varied in their cellular origin,... (Review)
Review
This chapter provides a comprehensive overview of malignant gliomas, the most common primary brain tumor in adults. These tumors are varied in their cellular origin, genetic profile, and morphology under the microscope, but together they share some of the most dismal prognoses of all neoplasms in the body. Although there is currently no cure for malignant glioma, persistent efforts to improve outcomes in patients with these tumors have led to modest increases in survival, and researchers worldwide continue to strive toward a deeper understanding of the factors that influence glioma development and response to treatment. In addition to well-established epidemiology, clinical manifestations, and common histopathologic and radiologic features of malignant gliomas, this section considers recent advances in molecular biology that have led to a more nuanced understanding of the genetic changes that characterize the different types of malignant glioma, as well as their implications for treatment. Beyond the traditional classification of malignant gliomas based on histopathological features, this chapter incorporates the World Health Organization's 2016 criteria for the classification of brain tumors, with special focus on disease-defining genetic alterations and newly established subcategories of malignant glioma that were previously unidentifiable based on microscopic examination alone. Traditional therapeutic modalities that form the cornerstone of treatment for malignant glioma, such as aggressive surgical resection followed by adjuvant chemotherapy and radiation therapy, and the studies that support their efficacy are reviewed in detail. This provides a foundation for additional discussion of novel therapeutic methods such as immunotherapy and convection-enhanced delivery, as well as new techniques for enhancing extent of resection such as fluorescence-guided surgery.
Topics: Adult; Humans; Glioma; Brain Neoplasms; Immunotherapy; Chemotherapy, Adjuvant
PubMed: 37452933
DOI: 10.1007/978-3-031-23705-8_1 -
Surgical Oncology Clinics of North... Oct 2022High-grade glioma is the most common malignant primary brain tumor in adults. Glioma infiltration renders it difficult to treat and likely to recur. Increasing the... (Review)
Review
High-grade glioma is the most common malignant primary brain tumor in adults. Glioma infiltration renders it difficult to treat and likely to recur. Increasing the extent of resection has been associated with improving progression-free survival and overall survival by several months. The introduction of 5-aminolevulinic acid (5-ALA) fluorescence-guided surgery has allowed surgeons to better differentiate between neoplastic tissue and normal tissue, thus achieving greater extent of resection. The development of new intraoperative imaging modalities in combination with 5-ALA may provide additional benefits for glioma patients.
Topics: Adult; Aminolevulinic Acid; Brain Neoplasms; Diagnostic Imaging; Glioma; Humans; Surgery, Computer-Assisted
PubMed: 36243495
DOI: 10.1016/j.soc.2022.06.002 -
Gene Apr 2022Glioma accounts for nearly 80% of all intracranial malignant tumors. It is a major challenge to society as it is causes to impaired brain function in many patients.... (Review)
Review
Glioma accounts for nearly 80% of all intracranial malignant tumors. It is a major challenge to society as it is causes to impaired brain function in many patients. Currently, gliomas are mainly treated with surgery, postoperative radiotherapy, and chemotherapy. However, the curative effects of these treatments are not satisfactory. Oncolytic virus (OV) is a novel treatment which works by activating the immune functions and inducing apoptosis of tumor cells. The OV propagates indefinitely in the host cell, eventually leading to the death of host cell. Subsequently, a large number of antigens and signal molecules are released which exert antitumor immunity. Several preclinical and clinical studies have shown that G207, DNX2401, Zika and other viruses have important roles in malignant tumors. For example, these viruses can reduce the growth of tumor cells without causing severe complications. However, the known OVs have not been clearly classified. Herein, we divided OVs into neurotropic and non-neurophilic OVs based on whether the OVs are naturally neurotropic or not. The therapeutic effects of each group were compared. Finally, challenges encountered in the clinical application of OVs in the treatment of malignant gliomas were summarized.
Topics: Animals; Glioma; Humans; Immunity; Models, Biological; Oncolytic Virotherapy; Oncolytic Viruses
PubMed: 35093451
DOI: 10.1016/j.gene.2022.146217 -
Viruses Jul 2021Glioblastoma is one of the most difficult tumor types to treat with conventional therapy options like tumor debulking and chemo- and radiotherapy. Immunotherapeutic... (Review)
Review
Glioblastoma is one of the most difficult tumor types to treat with conventional therapy options like tumor debulking and chemo- and radiotherapy. Immunotherapeutic agents like oncolytic viruses, immune checkpoint inhibitors, and chimeric antigen receptor T cells have revolutionized cancer therapy, but their success in glioblastoma remains limited and further optimization of immunotherapies is needed. Several oncolytic viruses have demonstrated the ability to infect tumors and trigger anti-tumor immune responses in malignant glioma patients. Leading the pack, oncolytic herpesvirus, first in its class, awaits an approval for treating malignant glioma from MHLW, the federal authority of Japan. Nevertheless, some major hurdles like the blood-brain barrier, the immunosuppressive tumor microenvironment, and tumor heterogeneity can engender suboptimal efficacy in malignant glioma. In this review, we discuss the current status of malignant glioma therapies with a focus on oncolytic viruses in clinical trials. Furthermore, we discuss the obstacles faced by oncolytic viruses in malignant glioma patients and strategies that are being used to overcome these limitations to (1) optimize delivery of oncolytic viruses beyond the blood-brain barrier; (2) trigger inflammatory immune responses in and around tumors; and (3) use multimodal therapies in combination to tackle tumor heterogeneity, with an end goal of optimizing the therapeutic outcome of oncolytic virotherapy.
Topics: Clinical Trials as Topic; Combined Modality Therapy; Glioblastoma; Glioma; Humans; Immunotherapy; Oncolytic Virotherapy; Oncolytic Viruses; Tumor Microenvironment
PubMed: 34372501
DOI: 10.3390/v13071294 -
Current Cancer Drug Targets 2017Recent publications on the molecular characterization of malignant glioma have had profound impact on the appreciation of tumoral heterogeneity within and between... (Review)
Review
Recent publications on the molecular characterization of malignant glioma have had profound impact on the appreciation of tumoral heterogeneity within and between patients. Both these phenomena are implicated in the variability in clinical outcome between patients, as well as the inevitable recurrence of these tumors after conventional treatment. The advent of selective cell culture protocols for the propagation of patient-derived glioma stem-like cells (GSCs) provides researchers the ability to selectively study the cells that could be at the root of tumor proliferation and resistance to therapy. As these techniques are widely applied in contemporary studies and becoming the preferred in vitro model, molecular characterization of GSCs is considered pivotal for the identification and advancement of novel therapies for this devastating disease. This review aims to provide an overview of canonical molecular alterations defining subtypes of malignant glioma as derived from genotypic, transcriptomic and epigenetic profiling in relation to their representation in GSC models. The distribution of these hallmark alterations as found in characterization studies of GSCs is compared between publications. Finally, conclusions of these studies with respect to coverage of driving alterations and translational relevance are provided. By doing so, we provide a contemporary overview of scientific results derived from GSC models and hopefully create appreciation of the advantages and caveats of utilizing these models for studying malignant glioma.
Topics: Biopsy; Cell Culture Techniques; Drug Screening Assays, Antitumor; Gene Expression Regulation, Neoplastic; Glioblastoma; Glioma; Humans; Methylation; Neoplastic Stem Cells; Tumor Cells, Cultured
PubMed: 27528360
DOI: 10.2174/1568009616666160813191809 -
Journal of Cellular and Molecular... Aug 2019Despite aggressive multimodality treatment, the prognosis of glioma, especially malignant glioma, remains very poor. After decades of effort, anti-angiogenic therapy has... (Review)
Review
Despite aggressive multimodality treatment, the prognosis of glioma, especially malignant glioma, remains very poor. After decades of effort, anti-angiogenic therapy has become an important method of cancer treatment in addition to surgery, radiotherapy and chemotherapy. Although the performance of anti-angiogenic therapy in colorectal cancer is good, its performance in malignant glioma remains unsatisfactory. Several phase III clinical trials showed no overall survival benefits. To solve this problem, the division of patients into groups based on their molecular biomarkers is an important step. This paper provides current insights into anti-angiogenic drugs undergoing clinical trials and discusses the potential of molecular biomarkers to guide glioma diagnosis.
Topics: Angiogenesis Inhibitors; Bevacizumab; Biomarkers, Tumor; Brain Neoplasms; Glioma; Humans; Indoles; Molecular Targeted Therapy; Prognosis; Snake Venoms
PubMed: 31210419
DOI: 10.1111/jcmm.14417 -
International Journal of Molecular... May 2021Malignant glioma represents a fatal disease with a poor prognosis and development of resistance mechanisms against conventional therapeutic approaches. The distinct... (Review)
Review
Malignant glioma represents a fatal disease with a poor prognosis and development of resistance mechanisms against conventional therapeutic approaches. The distinct tumor zones of this heterogeneous neoplasm develop their own microenvironment, in which subpopulations of cancer cells communicate. Adaptation to hypoxia in the center of the expanding tumor mass leads to the glycolytic and angiogenic switch, accompanied by upregulation of different glycolytic enzymes, transporters, and other metabolites. These processes render the tumor microenvironment more acidic, remodel the extracellular matrix, and create energy gradients for the metabolic communication between different cancer cells in distinct tumor zones. Escape mechanisms from hypoxia-induced cell death and energy deprivation are the result. The functional consequences are more aggressive and malignant behavior with enhanced proliferation and survival, migration and invasiveness, and the induction of angiogenesis. In this review, we go from the biochemical principles of aerobic and anaerobic glycolysis over the glycolytic switch, regulated by the key transcription factor hypoxia-inducible factor (HIF)-1α, to other important metabolic players like the monocarboxylate transporters (MCTs)1 and 4. We discuss the metabolic symbiosis model via lactate shuttling in the acidic tumor microenvironment and highlight the functional consequences of the glycolytic switch on glioma malignancy. Furthermore, we illustrate regulation by micro ribonucleic acids (miRNAs) and the connection between mutation status and glycolytic metabolism. Finally, we give an outlook about the diagnostic and therapeutic implications of the glycolytic switch and the relation to tumor immunity in malignant glioma.
Topics: Animals; Brain; Brain Chemistry; Brain Neoplasms; Carbonic Anhydrases; Glioma; Glycolysis; Humans; Hydrogen-Ion Concentration; Lactic Acid; Neovascularization, Pathologic; Tumor Microenvironment
PubMed: 34073734
DOI: 10.3390/ijms22115518 -
Neurosurgery Clinics of North America Jan 1990The many options neurologic surgeons have for the treatment of malignant gliomas are reviewed. Although virtually no malignant gliomal tumor can be cured by surgical... (Review)
Review
The many options neurologic surgeons have for the treatment of malignant gliomas are reviewed. Although virtually no malignant gliomal tumor can be cured by surgical resection alone, in the majority of cases, some combination of open resection or stereotactic surgery can produce a diagnosis, ameliorate symptoms, decrease the intracranial pressure, improve neurologic status, remove most of the tumor, and deliver other therapeutic agents. The techniques of both open resection and stereotactic surgery are discussed.
Topics: Brain Neoplasms; Combined Modality Therapy; Glioma; Humans; Stereotaxic Techniques; Survival Rate
PubMed: 2135973
DOI: No ID Found -
The Lancet. Oncology May 20065-Aminolevulinic acid is a non-fluorescent prodrug that leads to intracellular accumulation of fluorescent porphyrins in malignant gliomas-a finding that is under... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
5-Aminolevulinic acid is a non-fluorescent prodrug that leads to intracellular accumulation of fluorescent porphyrins in malignant gliomas-a finding that is under investigation for intraoperative identification and resection of these tumours. We aimed to assess the effect of fluorescence-guided resection with 5-aminolevulinic acid on surgical radicality, progression-free survival, overall survival, and morbidity.
METHODS
322 patients aged 23-73 years with suspected malignant glioma amenable to complete resection of contrast-enhancing tumour were randomly assigned to 20 mg/kg bodyweight 5-aminolevulinic acid for fluorescence-guided resection (n=161) or to conventional microsurgery with white light (n=161). The primary endpoints were the number of patients without contrast-enhancing tumour on early MRI (ie, that obtained within 72 h after surgery) and 6-month progression-free survival as assessed by MRI. Secondary endpoints were volume of residual tumour on postoperative MRI, overall survival, neurological deficit, and toxic effects. We report the results of an interim analysis with 270 patients in the full-analysis population (139 assigned 5-aminolevulinic acid, 131 assigned white light), which excluded patients with ineligible histological and radiological findings as assessed by central reviewers who were masked as to treatment allocation; the interim analysis resulted in termination of the study as defined by the protocol. Primary and secondary endpoints were analysed by intention to treat in the full-analysis population. The study is registered at http://www.clinicaltrials.gov as NCT00241670.
FINDINGS
Median follow-up was 35.4 months (95% CI 1.0-56.7). Contrast-enhancing tumour was resected completely in 90 (65%) of 139 patients assigned 5-aminolevulinic acid compared with 47 (36%) of 131 assigned white light (difference between groups 29% [95% CI 17-40], p<0.0001). Patients allocated 5-aminolevulinic acid had higher 6-month progression free survival than did those allocated white light (41.0% [32.8-49.2] vs 21.1% [14.0-28.2]; difference between groups 19.9% [9.1-30.7], p=0.0003, Z test). Groups did not differ in the frequency of severe adverse events or adverse events in any organ system class reported within 7 days after surgery.
INTERPRETATION
Tumour fluorescence derived from 5-aminolevulinic acid enables more complete resections of contrast-enhancing tumour, leading to improved progression-free survival in patients with malignant glioma.
Topics: Adult; Aged; Aminolevulinic Acid; Disease-Free Survival; Fluorescent Dyes; Glioma; Humans; Middle Aged; Neurosurgical Procedures; Treatment Outcome
PubMed: 16648043
DOI: 10.1016/S1470-2045(06)70665-9 -
Lasers in Surgery and Medicine Jul 2018Patients suffering from malignant gliomas have a poor prognosis. For the surgical treatment of these tumors, 5-aminolevulinic acid (5-ALA) has become a new standard. (Review)
Review
BACKGROUND
Patients suffering from malignant gliomas have a poor prognosis. For the surgical treatment of these tumors, 5-aminolevulinic acid (5-ALA) has become a new standard.
AIMS
This review intends to provide an overview over current status, significance, limitations, and future perspectives of 5-ALA based fluorescence guided surgery and photodynamic therapy for brain tumor patients.
MATERIALS AND METHODS
From peer reviewed publications on the many aspects connected with this topic, those with potential clinical relevance were selected and put in the context of our own experience.
RESULTS AND DISCUSSION
The high tumor selectivity of accumulation of fluorescent protoporphyrin IX (PpIX) after systemic administration of 5-ALA enables intra-operative fluorescence guidance, which is unimpaired by brainshift and does not require expensive equipment. The neurosurgical aim of complete resection of enhancing tumor can now more easily be achieved, which improves prognosis in these patients. Nevertheless, despite better surgery tumors will inevitably recur. In order to further prolong survival, the phototoxic properties of PpIX are presently being exploited in clinical trials of post-operative or interstitial photodynamic therapy (PDT).
CONCLUSION
5-ALA based fluorescence guidance and PDT offer an intriguing new option for the management of malignant gliomas. Lasers Surg. Med. 50:399-419, 2018. © 2018 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc.
Topics: Aminolevulinic Acid; Brain Neoplasms; Glioma; Humans; Photochemotherapy; Photosensitizing Agents
PubMed: 29737540
DOI: 10.1002/lsm.22933