The FDA's approval of bevacizumab for recurrent glioblastoma on May 9, 2009, was based on the significant response rate and clinical benefits seen from randomized phase II studies. Large-scale phase III data are unavailable. In an effort to determine benchmark efficacy parameters for bevacizumab and analyze its dose–response effect, the authors performed a meta-analysis of 15 studies published from 2005 to 2009, involving 548 patients with a median age of 53 years (range, 5–74 years), that used bevacizumab to treat recurrent glioblastoma. Median overall survival was 9.3 months (95% CI, 7.9–10.6 months). The respective 6-month progression-free and 6-month overall survival rates were 45% (95% CI, 34%–57%) and 76% (95% CI, 69%–84%), respectively. Median time to tumor progression was 6.1 months (95% CI, 4.2–8.1 months). The response analysis yielded a 6% complete response (95% CI, 2%–9%), 49% partial response (95% CI, 37%–61%), and 29% stable disease (95% CI, 20%–38%). No difference was seen in bevacizumab dose–response benefit between 5 mg/kg and 10 to 15 mg/kg. The efficacy benchmarks from this meta-analysis did not differ from those of the recently published randomized phase II studies. The lack of a dose–response effect would require confirmation in a prospectively conducted clinical trial. The FDA's approval of bevacizumab for recurrent glioblastoma on May 9, 2009, was based on the significant response rate and clinical benefits seen from randomized phase II studies. Large-scale phase III data are unavailable. In an effort to determine benchmark efficacy parameters for bevacizumab and analyze its dose–response effect, the authors performed a meta-analysis of 15 studies published from 2005 to 2009, involving 548 patients with a median age of 53 years (range, 5–74 years), that used bevacizumab to treat recurrent glioblastoma. Median overall survival was 9.3 months (95% CI, 7.9–10.6 months). The respective 6-month progression-free and 6-month overall survival rates were 45% (95% CI, 34%–57%) and 76% (95% CI, 69%–84%), respectively. Median time to tumor progression was 6.1 months (95% CI, 4.2–8.1 months). The response analysis yielded a 6% complete response (95% CI, 2%–9%), 49% partial response (95% CI, 37%–61%), and 29% stable disease (95% CI, 20%–38%). No difference was seen in bevacizumab dose–response benefit between 5 mg/kg and 10 to 15 mg/kg. The efficacy benchmarks from this meta-analysis did not differ from those of the recently published randomized phase II studies. The lack of a dose–response effect would require confirmation in a prospectively conducted clinical trial.

Background: Patients with recurrent glioblastoma have a poor outcome. Data from the phase III registration trial comparing tumour-treating alternating electric fields (TTFields) vs chemotherapy provided a unique opportunity to study dexamethasone effects on patient outcome unencumbered by the confounding immune and myeloablative side effects of chemotherapy. Methods: Using an unsupervised binary partitioning algorithm, we segregated both cohorts of the trial based on the dexamethasone dose that yielded the greatest statistical difference in overall survival (OS). The results were validated in a separate cohort treated in a single institution with TTFields and their T lymphocytes were correlated with OS. Results: Patients who used dexamethasone doses >4.1 mg per day had a significant reduction in OS when compared with those who used ⩽4.1 mg per day, 4.8 vs 11.0 months respectively (χ ²=34.6, P<0.0001) in the TTField-treated cohort and 6.0 vs 8.9 months respectively (χ ²=10.0, P4.1 mg per day was 3.2 months compared with those who used ⩽4.1 mg per day was 8.7 months (χ ²=11.1, P=0.0009). There was a significant correlation between OS and T-lymphocyte counts. Conclusions: Dexamethasone exerted profound effects on both TTFields and chemotherapy efficacy resulting in lower patient OS. Therefore, global immunosuppression by dexamethasone likely interferes with immune functions that are necessary for the treatment of glioblastoma.

Cerebrospinal fluid is routinely collected for the diagnosis and monitoring of patients with neurological malignancies. However, little is known as to how its constituents may change in a patient when presented with a malignant glioma. Here, we used a targeted mass-spectrometry based metabolomics platform using selected reaction monitoring with positive/negative switching and profiled the relative levels of over 124 polar metabolites present in patient cerebrospinal fluid. We analyzed the metabolic profiles from 10 patients presenting malignant gliomas and seven control patients that did not present malignancy to test whether a small sample size could provide statistically significant signatures. We carried out multiple unbiased forms of classification using a series of unsupervised techniques and identified metabolic signatures that distinguish malignant glioma patients from the control patients. One subtype identified contained metabolites enriched in citric acid cycle components. Newly diagnosed patients segregated into a different subtype and exhibited low levels of metabolites involved in tryptophan metabolism, which may indicate the absence of an inflammatory signature. Together our results provide the first global assessment of the polar metabolic composition in cerebrospinal fluid that accompanies malignancy, and demonstrate that data obtained from high throughput mass spectrometry technology may have suitable predictive capabilities for the identification of biomarkers and classification of neurological diseases.

BACKGROUND: Methotrexate‐based and alkylator‐based chemotherapy regimens are associated with renal and bone marrow toxicities, which limit their use in patients with central nervous system (CNS) lymphomas. The authors report their experience with an immunochemotherapy regimen consisting of rituximab and temozolomide in patients with primary or metastatic CNS lymphoma.METHODS: Seven patients who had received rituximab and temozolomide were identified from the database of the brain tumor clinic at the authors' institution: three patients had developed recurrent primary CNS lymphoma (PCNSL), one patient had newly diagnosed PCNSL but had poor renal function, and three other patients with systemic non‐Hodgkin lymphoma developed recurrent lymphoma in the brain only. Patients were scheduled to receive 4 cycles of induction rituximab on Day 1 and temozolomide on Days 1–5 of a 28‐day cycle. Thereafter, their treatment included a total of up to 8 maintenance cycles of temozolomide alone on Days 1–5 of a 28‐day cycle. A gadolinium‐enhanced magnetic resonance image of the head was obtained after every two cycles of treatment.RESULTS: All patients received rituximab without toxicity. Of the 4 patients who received induction temozolomide at doses > 150 mg/m² daily on Days 1–5, 2 experienced Grade 2 leukopenia and thrombocytopenia. Five patients achieved a radiographic complete response, and two patients had partial responses after induction treatment. The median response duration was 6 months (range 3–12+ months), and the median survival was 8 months (range 3+–12+ months).CONCLUSIONS: Although median survival was short, immunochemotherapy with rituximab and temozolomide was well tolerated and exhibited efficacy in this elderly and heavily pretreated cohort. The data obtained in the current study suggest that the optimal induction dose combination consists of rituximab 375 mg/m² on Day 1 and temozolomide 150 mg/m² daily on Days 1–5. Cancer 2004. © 2004 American Cancer Society.

Patients with intravascular lymphoma (IVL) frequently have neurological signs and symptoms. Prompt diagnosis and treatment is therefore crucial for their survival. However, the spectrum of neurological presentations and their respective frequencies have not been adequately characterized. Our aim is to document the spectrum of clinical symptoms and their respective frequencies and to create a clinical framework for the prompt diagnosis of IVL. A comprehensive meta-analysis of 654 cases of IVL published between 1957 and 2012 was performed to provide better insight into the neurological presentations of this disease. Neurologic complications were mainly divided into central nervous system (CNS) and peripheral nervous system (PNS) presentations. There were no differences in occurrences of CNS IVL based on gender or geographic locations (Asian Vs non-Asian). However, most patients with CNS IVL were younger than 70 years of age (p < 0.05). Our limited data do not support the treatment efficacy of methotrexate. CNS symptoms were seen in 42 % of all cases. The most common CNS complications identified were cognitive impairment/dementia (60.9 %), paralysis (22.2 %), and seizures (13.4 %). PNS complications were seen in 9.5 % of cases. Out of these, muscle weakness (59.7 %), neurogenic bladder (37.1 %), and paresthesia (16.1 %) were the most common presentations. CNS complications are more common among IVL patients. Out of these, dementia and seizures outnumber stroke-like presentations.