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Glioblastoma (GBM) is the most common malignant primary brain tumor in adults. Despite an established standard of care including surgical resection, radiation therapy, and chemotherapy, GBM unfortunately is associated with a dismal prognosis. Therefore, researchers are extensively evaluating avenues to expand GBM therapy and improve outcomes in patients with GBM. In this review, we provide a broad overview of novel GBM therapies that have recently completed or are actively undergoing study in clinical trials. These therapies expand across medical, surgical, and radiation clinical trials. We additionally review methods for improving clinical trial design in GBM. [ABSTRACT FROM AUTHOR]

Leptomeningeal disease (LMD) is a devastating sequelae of metastatic spread that affects approximately 5% of cancer patients. The incidence of LMD is increasing due to advancements in systemic therapy and enhanced detection methods. The purpose of this review is to provide a detailed overview of the evidence in the detection, prognostication, and treatment of LMD. A comprehensive literature search of PUBMED was conducted to identify articles reporting on LMD including existing data and ongoing clinical trials. We found a wide array of treatment options available for LMD including chemotherapy, targeted agents, and immunotherapy as well as several choices for radiotherapy including whole brain radiotherapy (WBRT), stereotactic radiosurgery (SRS), and craniospinal irradiation (CSI). Despite treatment, the prognosis for patients with LMD is dismal, typically 2–4 months on average. Novel therapies and combination approaches are actively under investigation with the aim of improving outcomes and quality of life for patients with LMD. Recent prospective data on the use of proton CSI for patients with LMD have demonstrated its potential survival benefit with follow-up investigations underway. There is a need for validated metrics to predict prognosis and improve patient selection for patients with LMD in order to optimize treatment approaches. [ABSTRACT FROM AUTHOR]

Isocitrate dehydrogenase (IDH) mutant gliomas are a primary malignancy of the central nervous system (CNS) malignancies, most commonly affecting adults under the age of 55. Standard of care therapy for IDH-mutant gliomas involves maximal safe resection, radiotherapy, and chemotherapy. However, despite good initial responses to multimodality treatment, recurrence is virtually universal. IDH-mutant gliomas represent a life-limiting prognosis. For this reason, there is a great need for novel treatments that can prolong survival. Uniquely for IDH-mutant gliomas, the IDH mutation is the direct driver of oncogenesis through its oncometabolite 2-hydroxygluterate. Inhibition of this mutated IDH with a corresponding reduction in 2-hydroxygluterate offers an attractive treatment target. Researchers have tested several IDH inhibitors in glioma through preclinical and early clinical trials. A phase III clinical trial of an IDH1 and IDH2 inhibitor vorasidenib yielded promising results among patients with low-grade IDH-mutant gliomas who had undergone initial surgery and no radiation or chemotherapy. However, many questions remain regarding optimal use of IDH inhibitors in clinical practice. In this review, we discuss the importance of IDH mutations in oncogenesis of adult-type diffuse gliomas and current evidence supporting the use of IDH inhibitors as therapeutic agents for glioma treatment. We also examine unresolved questions and propose potential directions for future research. [ABSTRACT FROM AUTHOR]

Despite decades of research and numerous clinical trials, the prognosis of patients diagnosed with glioblastoma (GBM) remains dire with median observed survival at 8 months. There is a critical need for novel treatments for GBM, which is the most common malignant primary brain tumor. Major advances in cancer therapeutics such as immune checkpoint inhibitors and chimeric antigen receptor (CAR) T-cell therapy have not yet led to improved outcomes for GBM. Conventional therapy of surgery followed by chemoradiation with or without tumor treating fields remains the standard of care. One of the many approaches to GBM therapy currently being explored is viral therapies. These typically work by selectively lysing target neoplastic cells, called oncolysis, or by the targeted delivery of a therapeutic transgene via a viral vector. In this review, we discuss the underlying mechanisms of action and describe both recent and current human clinical trials using these viruses with an emphasis on promising viral therapeutics that may ultimately break the field's current stagnant paradigm. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is the most common malignant primary brain tumor and confers a dismal prognosis. With only two FDA-approved therapeutics showing modest survival gains since 2005, there is a great need for the development of other disease-targeted therapies. Due, in part, to the profound immunosuppressive microenvironment seen in GBMs, there has been a broad interest in immunotherapy. In both GBMs and other cancers, therapeutic vaccines have generally yielded limited efficacy, despite their theoretical basis. However, recent results from the DCVax-L trial provide some promise for vaccine therapy in GBMs. There is also the potential that future combination therapies with vaccines and adjuvant immunomodulating agents may greatly enhance antitumor immune responses. Clinicians must remain open to novel therapeutic strategies, such as vaccinations, and carefully await the results of ongoing and future trials. In this review of GBM management, the promise and challenges of immunotherapy with a focus on therapeutic vaccinations are discussed. Additionally, adjuvant therapies, logistical considerations, and future directions are discussed. [ABSTRACT FROM AUTHOR]