Technological advances in the field of molecular genetics have improved the ability to classify brain tumors into subgroups with distinct clinical features and important therapeutic implications. The World Health Organization’s newest update on classification of gliomas (2016) incorporated isocitrate dehydrogenase 1 and 2 mutations, ATRX loss, 1p/19q codeletion status, and TP53 mutations to allow for improved classification of glioblastomas, low-grade and anaplastic gliomas. This paper reviews current advances in the understanding of diffuse glioma classification and the impact of molecular markers and DNA methylation studies on survival of patients with these tumors. We also discuss whether the classification and grading of diffuse gliomas should be based on histological findings, molecular markers, or DNA methylation subgroups in future iterations of the classification system.

Background: Bevacizumab has been used in recurrent glioblastoma (rGBM) since 2010 in Canada. Given its cost, potential toxicities, and unclear efficacy, further studies are required to better define suitable candidates for therapy. Methods: A single-center retrospective review of patients started on bevacizumab for rGBM from 2012 to 2015 was performed. Patient demographics, tumor characteristics, treatment regimen, and dates of clinical progression and death were collected. Overall survival (OS) and progression-free survival (PFS) were used as clinical outcomes and estimates. Radiological response was assessed using modified Response Assessment in Neuro-Oncology criteria. Results: A total of 80 patients were included. There were 67 reported deaths, and the median OS was 9.2 months (95% confidence interval [CI95%]=7.0-10.1 months), with a 12-month OS of 31% (CI95%=21.9-43.5%). Some 79 patients were included for analysis of clinical progression, among whom 61 had documented clinical progression. The median clinical PFS was 4.6 months (CI95%=3.8-6.4 months), and the 6-month clinical PFS was 39% (CI95%=29.0-52.9%). Addition of chemotherapy did not improve clinical outcomes. A total of 68 patients were included for radiological progression analysis, with 58 radiological progressions. The median radiological PFS was 5.8 months (CI95%=4.2-6.7 months), and the 6-month radiological PFS was 46% (CI95%=35.6-60.0%). Conclusions: This is the first reported Canadian experience with bevacizumab for rGBM. Our clinical outcomes are consistent with published data from multicenter phase II and III trials on bevacizumab in rGBM. More research is required to determine which subtype(s) of patients with rGBM could benefit from bevacizumab upon recurrence.

Background: When patients with cranial glioblastoma develop weakness, a rare differential diagnosis is spinal metastases. Methods: Chart and literature reviews were performed. Results: The reported patient had delayed onset spinal drop metastasis that was only detected by magnetic resonance imaging (MRI). A 48-year-old patient had supratentorial glioblastoma, treated with radiotherapy (RT) and concurrent temozolomide followed by six cycles of adjuvant temozolomide. Four years after completion of all treatments (62 months from initial presentation), he developed low backache and weakness in both legs. Positron emission tomography/computed tomography scans demonstrated intracranial recurrence only. Spinal drop metastases were detected only by MRI scan. Local spinal RT 40 Gy in 20 fractions with concurrent and maintenance temozolomide were given. Because of disease progression after nine cycles of temozolomide, systemic therapy was changed to bevacizumab, which greatly improved his symptoms for 4 months before deterioration of mental status. He is still alive with disease at 22 months after diagnosis of spinal metastases (84 months from initial glioblastoma diagnosis). Conclusions: MRI is the diagnostic imaging of choice for spinal metastases. This illustrative case of delayed-onset spinal metastases shows unusual slow progression. Local RT, temozolomide, and targeted therapy may improve survival. This illustrative case is the first report of bevacizumab as a second-line therapy in drop metastasis of glioblastoma.

A constellation of deficits, termed the cerebellar cognitive affective syndrome (CCAS), has been reported following acquired cerebellar lesions. We studied emotion identification and the cognitive control of emotion in children treated for acquired tumors of the cerebellum. Participants were 37 children (7–16 years) treated for cerebellar tumors (19 benign astrocytomas (AST), 18 malignant medulloblastomas (MB), and 37 matched controls (CON). The Emotion Identification Task investigated recognition of happy and sad emotions in music. In two cognitive control tasks, we investigated whether children could identify emotion in situations in which the emotion in the music and the emotion in the lyrics was either congruent or incongruent. Children with cerebellar tumors identified emotion as accurately and quickly as controls (p > .05), although there was a significant interaction of emotions and group (p < .01), with the MB group performing less accurately identifying sad emotions, and both cerebellar tumor groups were impaired in the cognitive control of emotions (p < .01). The fact that childhood acquired cerebellar tumors disrupt cognitive control of emotion rather than emotion identification provides some support for a model of the CCAS as a disorder, not so much of emotion as of the regulation of emotion by cognition. (JINS, 2010, 16, 1027–1038.)

Arterial spin labeling (ASL) uses magnetic resonance imaging methods to measure cerebral blood flow (CBF) non-invasively. ASL CBF validly localizes brain function and may be especially useful for studies where the time frame of behavioral change is more than a few minutes, such as in longitudinal and treatment studies. ASL measures of cerebral perfusion are highly accurate in detecting lesion laterality in temporal lobe epilepsy, stenotic-occlusive disease, and brain tumors. Among lesioned patients, ASL CBF has excellent concurrent validity when correlated with CBF measured by Positron Emission Tomography or with dynamic susceptibility-weighted magnetic resonance. ASL CBF can predict tumor grading in vivo and can predict six-month response to the surgical treatment of brain tumors. ASL's capability to selectively and non-invasively tag flow in major vessels may refine the monitoring of treatment of cerebrovascular disease and brain tumors. Conclusions about the utility of ASL are limited by the small sample sizes of the studies currently in the literature and by the uncertainty caused by the effect of brain disease on transit times of the magnetic tag. As the method evolves, ASL techniques will likely become more widely used in clinical research and practice. (JINS, 2007, 13, 526–538.)