Faculty Bibliography

Glioblastoma multiforme constitutes the most common primary brain tumor and carries a grim prognosis for patients treated with conventional therapy including surgery, radiation therapy, and chemotherapy. There has been a recent revival of selective intra-arterial delivery of targeted agents for the treatment of glioblastoma multiforme. Because these agents are less toxic and their delivery leads to a higher tumor-drug concentration, this combination may provide a better outcome in patients with high-grade glioma. This article discusses early experiences in patients who received superselective intra-arterial cerebral infusion of bevacizumab, cetuximab, and temozolamide after blood-brain barrier disruption with mannitol.

We present neuroimages for a patient in a locked-in state with reversed flow in the anterior spinal artery as a result of bilateral distal vertebral artery occlusion. Following vertebral artery stenting, there is markedly improved flow in the posterior circulation and significant neurological recovery.

In this article, a detailed description of the normal arterial supply and venous drainage of the spinal cord is provided, and the role of catheter angiography and MR angiography in depicting the vascular anatomy of the spinal cord is discussed.

BACKGROUND: This prospective, single-center study assesses progression-free survival (PFS) and overall survival (OS) in patients with recurrent glioblastoma multiforme (GBM) treated with a single dose of superselective intra-arterial cerebral infusion (SIACI) of bevacizumab (BV) after blood-brain barrier disruption (BBBD). Patients were initially enrolled in our phase I study, for which the primary end point was to determine the safety and maximum tolerated dose of SIACI BV. METHODS: Fourteen patients with recurrent GBM were recruited between August 2009 and November 2010 after failing the standard treatment with radiation therapy and temozolomide. None of these patients were previously treated with BV. After receiving a single dose of IA BV (2 to 15 mg/kg), standard IV BV chemotherapy was continued in 12 of 14 patients (86%). The recently updated Response Assessment in Neuro-Oncology Working Group (RANO) criteria were used to evaluate PFS, and the Kaplan-Meier estimator was used to evaluate PFS and OS. RESULTS: Using RANO criteria, the median PFS in these patients was 10 months. The median OS estimation for this cohort was 8.8 months. The OS was less than the PFS because 4 patients died without progressing. Toxicity attributed to the IA BV treatment was present in 2 patients (wound dehiscence and rash). Another patient suffered from seizures 1 week after the SIACI procedure; however, this patient had epilepsy before and seizure type/frequency were similar before and after therapy. CONCLUSIONS: Our study shows that for patients naive to BV, a single dose of SIACI BV after BBBD followed by IV BV offers an encouraging outcome in terms of PFS when compared with previous trials using IV BV with and without concomitant irinotecan (CPT-11). Larger phase II trials are warranted to determine whether repeated IA BV alone is superior to IV BV for recurrent GBM.

Ependymoma is a central nervous system tumor associated with a poor prognosis due to limited efficacy of current medical treatment modalities, often resulting in multiple surgical re-resections with each tumor recurrence. As traditional chemotherapeutic regimens have proved unsuccessful in long-term control of subtotally resected ependymoma, other agents targeting the tumor microenvironement including the angiogenic factors supplying neovascularization have recently been used. Anti-angiogenic agents such as bevacizumab are routinely used in adult patients with recurrent glioma. Selective intra-arterial cerebral infusion (SIACI) of biological agents within tumor-supplying cerebral vasculature has recently been re-examined as a means to avoid the systemic side-effects associated with intravenous use of bevacizumab. This technical paper describes the first reported use of SIACI for delivery of two targeted biologic agents, bevacizumab and cetuximab in a pediatric patient utilizing the basilar artery to selectively administer the drugs to the tumor microenvironment. We believe this method for therapeutic delivery will both broaden treatment options and better refine treatment methodology as the multi-modality treatment approach often required to treat patients with pediatric ependymomas and other intracranial malignancies evolves.

BACKGROUND:: Despite increasing acceptance of endovascular coiling for treating intracranial aneurysms, incomplete occlusion remains a limitation. Attempts to reduce recanalization have prompted creation of polyglycolic/polylactic acid coated (Matrix) coils shown to improve neointima formation; however, previous publications demonstrate conflicting results regarding their efficacy. Few studies account for factors influencing recurrence and only four studies include bare platinum (BP) control groups. Objective: To compare initial, short, and mid-term occlusion as well as retreatment rates using Matrix versus BP coils. METHODS:: Retrospective review of patients undergoing coiling of cerebral aneurysms from 2001-2005 was performed. Analysis included a multivariate logistic regression model designed to detect a 35% absolute difference in initial occlusion between coil treatment groups with 80% power. RESULTS:: Complete initial occlusion was achieved in 64% of BP (n=45) and 63% of Matrix (n=56) cases (p=1.0). Follow-up occlusion rates in the short-term and mid-term were 52% and 60% for BP and 42% and 67% for Matrix cases (p=.24;p=.38), respectively. After adjusting for size, morphology, volumetric packing density, location, rupture, and balloon remodeling, no difference in initial and subsequent occlusion or retreatment rates for BP versus Matrix coils was appreciated. CONCLUSION:: After controlling for factors influencing recanalization, the present investigation failed to show a significant difference between coil groups

Intra-arterial (IA) chemotherapy for malignant gliomas including glioblastoma multiforme was initiated decades ago, with many preclinical and clinical studies having been performed since then. Although novel endovascular devices and techniques such as microcatheter or balloon assistance have been introduced into clinical practice, the question remains whether IA therapy is safe and superior to other drug delivery modalities such as intravenous (IV) or oral treatment regimens. This review focuses on IA delivery and surveys the available literature to assess the advantages and disadvantages of IA chemotherapy for treatment of malignant gliomas. In addition, we introduce our hypothesis of using IA delivery to selectively target cancer stem cells residing in the perivascular stem cell niche.

BACKGROUND:: Arteriovenous malformations (AVM) with associated aneurysms (AA) increase hemorrhagic risk in adults. Associated aneurysms are thought to develop over time, and the incidence in children is therefore thought to be minimal but thus far has not been studied. OBJECT:: To define the incidence and morbidity of AA in children, and to assess the results of our treatment strategy. METHODS:: Patients less than 18 years of age with pial AVM were reviewed from 2000 to 2009. Demographics, presentation, hemorrhage, associated aneurysms, treatment method, and outcome were analyzed. RESULTS:: Of 144 patients with AVM, 30 were less than 18 years. AA was identified in 5/30 (16.7%) children and 33/114 (28.9%) adults. (p=0.25) Mean age at presentation was 11.67 years (range 6mo-17yrs), and mean follow up was 28.8 months (range 1 - 75 months). Hemorrhage at presentation was 80% with AA and 72% with AVM alone. Emergent therapy was required in 60% of patients with AA and 40% with AVM alone (p=0.63). Time to treatment was 4.3 days with AA and 27.3 days without (p=0.42). There was no difference in outcome between patients with AA and AVM alone. CONCLUSION:: The incidence of pediatric AA was higher in our series than projected in the current literature. Time to treatment was shorter in children with AA compared with AVM alone, although there was no difference in clinical outcome. While hemorrhage rates were similar, emergent therapy was required more frequently in patients with AA. Our findings support the need for early diagnosis and treatment of associated aneurysms in children