Abstract
BackgroundPrimary central nervous system lymphomas (PCNSL) are rare and aggressive CNS tumors. Current management involves high-dose methotrexate (HD-MTX) typically administered intravenously (IV), despite the existence of the blood-brain barrier (BBB), which significantly decreases its bioavailability. Cerebral intra-arterial chemotherapy (CIAC) coupled with osmotic BBB disruption (OBBBD) can theoretically circumvent this issue.MethodsWe performed a retrospective analysis of patients with newly diagnosed PCNSL treated with HD-MTX-based CIAC+OBBBD at our center between November 1999 and May 2018. OBBBD was achieved using a 25% mannitol intra-arterial infusion. Patients were followed clinically and radiologically every month until death or remission. Demographics, clinical and outcome data were collected from the medical record. All imaging studies were reviewed for evidence of complication and outcome assessment. Kaplan-Meier analyses were used to compute remission, progression-free survival (PFS) as well as overall survival times. Subgroup analyses were performed using the log rank test.ResultsForty-four patients were included in the cohort. Median follow-up was 38 months. Complete response was achieved in 34 patients (79%) at a median of 7.3 months. Actuarial median survival and PFS were 45 months and 24 months, respectively. Age, ECOG and lesion location did not impact outcome. Complications included thrombocytopenia (39%), neutropenia (20%), anemia (5%), seizures (11%), stroke (2%), and others (20%).ConclusionCIAC using HD-MTX-based protocols with OBBBD is a safe and well-tolerated procedure for the management of PCNSL. Our data suggests better PFS and survival outcomes compared to IV protocols with less hematologic toxicity and good tolerability, especially in the elderly.
Highlights
Primary central nervous system lymphomas (PCNSL) are considered a rare and aggressive form of central nervous system (CNS) tumors, accounting for 1% of lymphomas and representing 4% of primary brain tumors [1, 2]
Looking at PCNSL median survival over the last decades, the outcome of patients has significantly improved, doubling from 12.5 months in the 1970s to 26 months in the 2010s. This is only true for patients younger than 70 years, as median survival has not changed in older patients, remaining dismal at around 7 months [13]
17 were excluded from the analysis: one pediatric patient, four patients secondarily referred to our institution after having received prior systemic chemotherapy at another, five patients with systemic lymphomas and seven patients initially treated with an IV HDMTX regimens (Figure 1)
Summary
Primary central nervous system lymphomas (PCNSL) are considered a rare and aggressive form of central nervous system (CNS) tumors, accounting for 1% of lymphomas and representing 4% of primary brain tumors [1, 2]. Eyes and/ or cerebrospinal fluid, these extra nodal non-Hodgkin large B cell lymphomas typically show no evidence of systemic diffusion. Untreated, they present a median survival of only 3 months [3]. One major characteristic of these lesions is their sensitivity to both chemotherapy and radiotherapy [4,5,6,7,8] Using these two modalities in various combinations, the initial overall response rate is in the range of 70%–80% [9,10,11]. Cerebral intra-arterial chemotherapy (CIAC) coupled with osmotic BBB disruption (OBBBD) can theoretically circumvent this issue
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