title: Long-term cognitive function, neuroimaging, and quality of life in primary CNS lymphoma.
abstract: OBJECTIVE
  To describe and correlate neurotoxicity indicators in long-term primary CNS lymphoma (PCNSL) survivors who were treated with high-dose methotrexate-based regimens with or without whole-brain radiotherapy (WBRT).
  
  
  METHODS
  Eighty PCNSL survivors from 4 treatment groups (1 with WBRT and 3 without WBRT) who were a minimum of 2 years after diagnosis and in complete remission underwent prospective neuropsychological, quality-of-life (QOL), and brain MRI evaluation. Clinical characteristics were compared among treatments by using the χ(2) test and analysis of variance. The association among neuroimaging, neuropsychological, and QOL outcomes was assessed by using the Pearson correlation coefficient.
  
  
  RESULTS
  The median interval from diagnosis to evaluation was 5.5 years (minimum, 2 years; maximum, 26 years). Survivors treated with WBRT had lower mean scores in attention/executive function (p = 0.0011), motor skills (p = 0.0023), and neuropsychological composite score (p = 0.0051) compared with those treated without WBRT. Verbal memory was better in survivors with longer intervals from diagnosis to evaluation (p = 0.0045). On brain imaging, mean areas of total T2 abnormalities were different among treatments (p = 0.0006). Total T2 abnormalities after WBRT were more than twice the mean of any non-WBRT group and were associated with poorer neuropsychological and QOL outcomes.
  
  
  CONCLUSIONS
  Our results suggest that in patients treated for PCNSL achieving complete remission and surviving at least 2 years, the addition of WBRT to methotrexate-based chemotherapy increases the risk of treatment-related neurotoxicity. Verbal memory may improve over time.
  
  
  METHODS
  This study provides Class III evidence that in patients treated for PCNSL achieving complete remission and surviving at least 2 years, the addition of WBRT to methotrexate-based chemotherapy increases the risk of treatment-related neurotoxicity.
authors.affiliation: Oregon Health & Science University, Portland, OR, USA.
authors.forename: Nancy D
authors.initials: ND
authors.lastname: Doolittle
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Korfel
authors.forename: Meredith A
authors.initials: MA
authors.lastname: Lubow
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Schorb
authors.forename: Uwe
authors.initials: U
authors.lastname: Schlegel
authors.forename: Sabine
authors.initials: S
authors.lastname: Rogowski
authors.forename: Rongwei
authors.initials: R
authors.lastname: Fu
authors.forename: Edit
authors.initials: E
authors.lastname: Dósa
authors.forename: Gerald
authors.initials: G
authors.lastname: Illerhaus
authors.forename: Dale F
authors.initials: DF
authors.lastname: Kraemer
authors.forename: Leslie L
authors.initials: LL
authors.lastname: Muldoon
authors.forename: Pasquale
authors.initials: P
authors.lastname: Calabrese
authors.forename: Nancy
authors.initials: N
authors.lastname: Hedrick
authors.forename: Rose Marie
authors.initials: RM
authors.lastname: Tyson
authors.forename: Kristoph
authors.initials: K
authors.lastname: Jahnke
authors.forename: Leeza M
authors.initials: LM
authors.lastname: Maron
authors.forename: Robert W
authors.initials: RW
authors.lastname: Butler
authors.forename: Edward A
authors.initials: EA
authors.lastname: Neuwelt
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use*; D016543:Central Nervous System Neoplasms / Q000473:pathology / Q000628:therapy*; D059248:Chemoradiotherapy; D003071:Cognition / Q000187:drug effects*; D006801:Humans; D008223:Lymphoma / Q000473:pathology / Q000628:therapy*; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use*; D059906:Neuroimaging / Q000379:methods; D009483:Neuropsychological Tests; D011446:Prospective Studies; D011788:Quality of Life
chemical_list: D000964:Antimetabolites, Antineoplastic; D008727:Methotrexate