title: Primary CNS lymphoma treated with osmotic blood-brain barrier disruption: prolonged survival and preservation of cognitive function.
abstract: Combination chemotherapy with or without radiotherapy has had only modest efficacy in the treatment of primary CNS lymphoma. Median survival of these patients, treated primarily with radiotherapy, is 13 months; 5-year survival is less than 5%. Thirty consecutive non-acquired immune deficiency syndrome patients with primary CNS lymphoma were treated with barrier-dependent chemotherapy using intraarterial mannitol to open the blood-brain barrier (BBB). Follow-up included extensive neuropsychologic testing of all patients. Thirteen patients received cranial radiation 1 to 9 months before referral (group 1). Seventeen patients received initial BBB disruption chemotherapy with subsequent radiation only for tumor progression or recurrence (group 2). The difference in median survivals from diagnosis--17.8 months for group 1 and 44.5 months for group 2--was statistically significant (P = .039). Group 1 survival is comparable with the 20-month median survival of a historical series of patients (n = 208) treated with radiotherapy with or without chemotherapy. Group 2 patient survival represents an advance in the survival of CNS lymphoma and was associated with preservation of cognitive function in six of seven nonirradiated complete responders observed for 1 to 7 years. Patient toxicity was manageable in this intensive therapeutic regimen. In this series, a plateau in survival curves suggests that a major portion of these patients may be cured without the neuropsychologic sequelae associated with cranial radiation.
authors.affiliation: Department of Neurology, Oregon Health Sciences University, Portland 97201-3098.
authors.forename: E A
authors.initials: EA
authors.lastname: Neuwelt
authors.forename: D L
authors.initials: DL
authors.lastname: Goldman
authors.forename: S A
authors.initials: SA
authors.lastname: Dahlborg
authors.forename: J
authors.initials: J
authors.lastname: Crossen
authors.forename: F
authors.initials: F
authors.lastname: Ramsey
authors.forename: S
authors.initials: S
authors.lastname: Roman-Goldstein
authors.forename: R
authors.initials: R
authors.lastname: Braziel
authors.forename: B
authors.initials: B
authors.lastname: Dana
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001812:Blood-Brain Barrier; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D003071:Cognition; D003520:Cyclophosphamide / Q000008:administration & dosage; D003907:Dexamethasone / Q000008:administration & dosage; D005260:Female; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008223:Lymphoma / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D009483:Neuropsychological Tests; D011344:Procarbazine / Q000008:administration & dosage; D011379:Prognosis; D016016:Proportional Hazards Models; D015996:Survival Rate
chemical_list: D011344:Procarbazine; D003907:Dexamethasone; D003520:Cyclophosphamide; D002955:Leucovorin; D008727:Methotrexate