title: Blood-brain barrier disruption and intra-arterial methotrexate-based therapy for newly diagnosed primary CNS lymphoma: a multi-institutional experience.
abstract: 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.
authors.affiliation: 3181 SW Sam Jackson Park Rd, Mailcode L603, Portland, OR 97239, USA.
authors.forename: Lilyana
authors.initials: L
authors.lastname: Angelov
authors.forename: Nancy D
authors.initials: ND
authors.lastname: Doolittle
authors.forename: Dale F
authors.initials: DF
authors.lastname: Kraemer
authors.forename: Tali
authors.initials: T
authors.lastname: Siegal
authors.forename: Gene H
authors.initials: GH
authors.lastname: Barnett
authors.forename: David M
authors.initials: DM
authors.lastname: Peereboom
authors.forename: Glen
authors.initials: G
authors.lastname: Stevens
authors.forename: John
authors.initials: J
authors.lastname: McGregor
authors.forename: Kristoph
authors.initials: K
authors.lastname: Jahnke
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Lacy
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Hedrick
authors.forename: Edna
authors.initials: E
authors.lastname: Shalom
authors.forename: Sandra
authors.initials: S
authors.lastname: Ference
authors.forename: Susan
authors.initials: S
authors.lastname: Bell
authors.forename: Lisa
authors.initials: L
authors.lastname: Sorenson
authors.forename: Rose Marie
authors.initials: RM
authors.lastname: Tyson
authors.forename: Marianne
authors.initials: M
authors.lastname: Haluska
authors.forename: Edward A
authors.initials: EA
authors.lastname: Neuwelt
mesh_terms: D000964:Antimetabolites, Antineoplastic; D001812:Blood-Brain Barrier / Q000502:physiology*; D001932:Brain Neoplasms / Q000175:diagnosis / Q000503:physiopathology; D016543:Central Nervous System Neoplasms / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D018572:Disease-Free Survival; D016503:Drug Delivery Systems; D006801:Humans; D007261:Infusions, Intra-Arterial / Q000379:methods*; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy / Q000378:metabolism; D008727:Methotrexate / Q000008:administration & dosage* / Q000627:therapeutic use; D009995:Osmosis; D011379:Prognosis; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D008727:Methotrexate