Glioma is the most common form of primary malignant brain tumor in adults, with approximately 4 cases per 100 000 people each year. Gliomas, like many tumors, are thought to primarily metabolize glucose for energy production; however, the reliance upon glycolysis has recently been called into question. In this study, we aimed to identify the metabolic fuel requirements of human glioma cells.
Meningiomas are the most common primary intracranial tumors in adults. Identification of SMO and AKT1 mutations in meningiomas has raised the hope for targeted therapies. It would be useful to know the precise frequency of these mutations in anatomical subgroups and clarify their prognostic value.
In previous clinical trials, antiangiogenic therapies such as bevacizumab did not show efficacy in patients with newly diagnosed glioblastoma (GBM). This may be a result of the heterogeneity of GBM, which has a variety of imaging-based phenotypes and gene expression patterns. In this study, we sought to identify a phenotypic subtype of GBM patients who have distinct tumor-image features and molecular activities and who may benefit from antiangiogenic therapies.
BackgroundSpinal astrocytomas are rare intramedullary CNS tumors for which there is limited consensus on treatment; the importance of the extent of resection (EOR), postoperative radiotherapy, and chemotherapy remains poorly understood. We report on outcomes associated with surgery, postoperative radiotherapy, and chemotherapy in a series of patients treated at M. D. Anderson Cancer Center (MDACC) with the aim of elucidating the role of these treatments in spinal astrocytomas.MethodsWe retrospectively reviewed charts from a series of 83 patients with histologically confirmed spinal astrocytoma treated at MDACC during 1990-2011. Data collected included patient demographic characteristics, prognostic indicators, and treatment modality at diagnosis. We analyzed overall survival (OS) and progression-free survival (PFS) for pilocytic (World Health Organization [WHO] grade I) and infiltrative (WHO grades II, III, and IV) astrocytomas, separately. Multivariate analysis was performed for the infiltrative patients but not the pilocytic patients because of a limited number of cases.ResultsHigher WHO grade among all patients was associated with worse OS (P < .0001) and PFS (P = .0003). Among patients with infiltrative tumors, neither EOR nor radiotherapy was associated with a difference in outcomes in multivariate analysis; however, among patients with infiltrative astrocytomas, chemotherapy was significantly associated with improved PFS (hazard ratio = .22, P = .0075) but not OS (hazard ratio = .89, P = .83) in multivariate analysis.ConclusionWHO grade was the strongest prognostic indicator in patients with spinal cord astrocytomas. Our results also show that chemotherapy improved PFS in infiltrative astrocytomas in multivariate analysis, but neither EOR nor radiation therapy influenced outcomes in this group.
Toca 511, a gamma retroviral replicating vector encoding cytosine deaminase, used in combination with 5-fluorocytosine (5-FC) kills tumor by local production of 5-fluorouracil (5-FU), inducing local and systemic immunotherapeutic response resulting in long-term survival after cessation of 5-FC. Toca 511 and Toca FC (oral extended-release 5-FC) are under investigation in patients with recurrent high-grade glioma. Lomustine is a treatment option for patients with high-grade glioma.
Tumor treating fields (TTFields) are low-intensity electric fields alternating at an intermediate frequency (200kHz), which have been demonstrated to block cell division and interfere with organelle assembly. This novel treatment modality has shown promise in a variety of tumor types. It has been evaluated in randomized phase 3 trials in glioblastoma (GBM) and demonstrated to prolong progression-free survival (PFS) and overall survival (OS) when administered together with standard maintenance temozolomide (TMZ) chemotherapy in patients with newly diagnosed GBM. TTFields are continuously delivered by 4 transducer arrays consisting each of 9 insulated electrodes that are placed on the patient’s shaved scalp and connected to a portable device. Here we summarize the preclinical data and mechanism of action, the available clinical data, and further outlook of this treatment modality in brain tumors and other cancer indications.
Clinical genomics platforms are needed to identify targetable alterations, but implementation of these technologies and best practices in routine clinical pediatric oncology practice are not yet well established.
Identification of genetic changes in CNS tumors is important for the appropriate clinical management of patients. Our objective was to develop a next-generation sequencing (NGS) assay for simultaneously detecting the various types of genetic alterations characteristic for adult and pediatric CNS tumors that can be applied to small brain biopsies.
The clinical management/understanding of brain metastases (BM) has changed substantially in the last 5 years, with key advances and clinical trials highlighted in this review. Several of these changes stem from improvements in systemic therapy, which have led to better systemic control and longer overall patient survival, associated with increased time at risk for developing BM. Development of systemic therapies capable of preventing BM and controlling both intracranial and extracranial disease once BM are diagnosed is paramount. The increase in use of stereotactic radiosurgery alone for many patients with multiple BM is an outgrowth of the desire to employ treatments focused on local control while minimizing cognitive effects associated with whole brain radiotherapy. Complications from BM and their treatment must be considered in comprehensive patient management, especially with greater awareness that the majority of patients do not die from their BM. Being aware of significant heterogeneity in prognosis and therapeutic options for patients with BM is crucial for appropriate management, with greater attention to developing individual patient treatment plans based on predicted outcomes; in this context, recent prognostic models of survival have been extensively revised to incorporate molecular markers unique to different primary cancers.
Brain-derived neurotrophic factor (BDNF), a neurotrophin that regulates neuronal function and development, is implicated in several neurodegenerative conditions. Preliminary data suggest that a reduction of BDNF concentrations may lead to postchemotherapy cognitive impairment. We hypothesized that a single nucleotide polymorphism (rs6265) of the BDNF gene may predispose patients to cognitive impairment. This study aimed to evaluate the effect of BDNF gene polymorphism on chemotherapy-associated cognitive impairment.