Blood-brain barrier disruption and intra-arterial methotrexate-based therapy for newly diagnosed primary CNS lymphoma: a multi-institutional experience.

PURPOSE Primary CNS lymphoma (PCNSL) is confined to the CNS and/or the eyes at presentation and is usually initially treated with intravenous methotrexate-based chemotherapy and whole-brain radiotherapy (WBRT). However, the intact blood-brain barrier (BBB) can limit diffusion of methotrexate into brain and tumor. With BBB disruption (BBBD), enhanced drug delivery to the tumor can be achieved. PATIENTS AND METHODS This report summarizes the multi-institutional experience of 149 newly diagnosed (with no prior WBRT) patients with PCNSL treated with osmotic BBBD and intra-arterial (IA) methotrexate at four institutions from 1982 to 2005. In this series, 47.6% of patients were age > or = 60 years, and 42.3% had Karnofsky performance score (KPS) less than 70 at diagnosis. Results The overall response rate was 81.9% (57.8% complete; 24.2% partial). Median overall survival (OS) was 3.1 years (25% estimated survival at 8.5 years). Median progression-free survival (PFS) was 1.8 years, with 5-year PFS of 31% and 7-year PFS of 25%. In low-risk patients (age < 60 years and KPS > or = 70), median OS was approximately 14 years, with a plateau after approximately 8 years. Procedures were generally well tolerated; focal seizures (9.2%) were the most frequent side effect and lacked long-term sequelae. CONCLUSION This large series of patients treated over a 23-year period demonstrates that BBBD/IA methotrexate-based chemotherapy results in successful and durable tumor control and outcomes that are comparable or superior to other PCNSL treatment regimens.

Perioperative complications of blood brain barrier disruption under general anesthesia: a retrospective review.

Blood brain barrier disruption enhances drug delivery in primary central nervous system lymphoma. In this study, we report adverse events that were encountered intraoperatively and in the postoperative period in these patients. A retrospective analysis of 17 patients documenting demographic data, preprocedure medical history, intraoperative, and postoperative anesthetic complications was conducted between January 2002 and December 2004. Seventeen patients underwent 210 treatments under general anesthesia with a mean of 12.4+/-7.2 treatments per patient. Focal seizures occurred in 13% of patients. Generalized motor seizures occurred in 4 treatment sessions in 2 different patients. The incidence of seizures was significantly higher when the internal carotid artery was used for injection, as opposed to the vertebral artery (20.8% and 6.02%, respectively, P=0.0034). Tachycardia associated with ST segment depression occurred 9 times (4.3%) in 3 patients. One patient had significant ST segment elevation (more than 1.5 mm). Transient cerebral vasospasm after methotrexate injection occurred in 9% of patients. Postoperative nausea and vomiting were observed in 11.9% of patients. After emergence, lethargy and obtundation occurred in 7.6% of the cases. The incidence of postoperative headache and reversible motor deficits was 6% and 3.8%, respectively. Our review highlights the problems that were encountered during blood brain barrier disruption under anesthesia and in the postoperative period. Further prospective studies are required for comprehensive evaluation of intraprocedure and postprocedure complications that will allow development of an optimal anesthetic plan and will improve patient outcome by preventing potential complications.

Maculopathy as a complication of blood-brain barrier disruption in patients with central nervous system lymphoma.

PURPOSE: To report on the development of visually significant maculopathy associated with blood-brain barrier disruption (BBBD) therapy for the treatment of central nervous system (CNS) lymphoma. DESIGN: Retrospective case series. METHODS: Chart review of 20 patients undergoing BBBD therapy for treatment of CNS lymphoma at the Cleveland Clinic. Patients with documented maculopathy were included in analysis. RESULTS: Seven (54%) of 13 patients were identified with new macular retinal pigment epithelium (RPE) changes after BBBD treatment. The RPE changes consisted of fine clumps of hyperpigmentation in the foveal region associated with variable degrees of RPE loss. These changes were bilateral but often asymmetric. Two patients had decreased visual acuity resulting from maculopathy. One patient had documented progression of maculopathy after completion of treatment. CONCLUSIONS: Maculopathy is a frequent finding after BBBD therapy for CNS lymphoma.