Long-term cognitive function, neuroimaging, and quality of life in primary CNS lymphoma.

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. CLASSIFICATION OF EVIDENCE: 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.

Computer-based assessment of cognitive functions in brain tumor patients.

NeuroCogFX is a short yet comprehensive computer-based neuropsychological battery of tests developed to investigate neurological patients for cognitive dysfunction after potentially neurotoxic therapy. NeuroCogFX had been standardized in a group of 242 healthy controls (Fliessbach et al., Fortschr Neurol Psychiatr 74:643-650, 2006). The present study was conducted to assess the practicability, reliability, and validity of NeuroCogFX in brain tumor patients without active disease after tumor-directed therapy. To evaluate its validity, neuropsychological testing with NeuroCogFX was completed parallel to a battery of established neuropsychological tests in 54 patients with different types of brain tumors and without active disease for at least 6 months. Retest reliability was assessed in a different sample of 49 patients with gliomas. Results showed good practicability with a median test duration of 28 min (range 16-51 min). Most subtests showed medium-sized retest reliability in healthy controls and tumor patients, with the exception of the 2-back test and reaction time measures in tumor patients. Convergent validity was confirmed for the domains psychomotor speed, verbal memory, and verbal short-term memory. NeuroCogFX enables serial scientific neuropsychological assessment of brain tumor patients. It can be carried out within a short period of time by non-academic personnel and is therefore applicable to large cohorts, e.g., within clinical trials.

Long-term survival with favorable cognitive outcome after chemotherapy in primary central nervous system lymphoma.

OBJECTIVE: To evaluate long-term progression-free survival and overall survival, quality of life, and cognitive function in primary central nervous system lymphoma after systemic and intraventricular chemotherapy without radiotherapy. METHODS: A long-term follow-up was conducted on surviving primary central nervous system lymphoma patients having been enrolled in a pilot/phase II trial between September 1995 and December 2001. Initially, 65 patients (median age, 62 years) had been treated with systemic and intraventricular chemotherapy without radiotherapy. All living patients were contacted, and a neurological examination, comprehensive neuropsychological testing, quality-of-life assessment, and imaging were performed. RESULTS: Twenty-one of all 65 patients (32 %) and 17 of 30 patients 60 years or younger (57%), respectively, were still alive at median follow-up of 100 months (range, 77-149 months). Nineteen of 21 patients completed all investigations; 1 was lost to follow-up. In three patients, an exclusively extraneural relapse of a high-grade non-Hodgkin's lymphoma was diagnosed after 9, 31, and 40 months, respectively. All of them experienced complete remission to high dose. Neither late neurotoxicity nor compromise of quality of life was found in any of the patients examined. INTERPRETATION: Primary polychemotherapy based on high-dose methotrexate (MTX) and cytarabine (Ara-C) is highly efficient in treatment of primary central nervous system lymphoma. About half of patients 60 years or younger can obviously be cured with this regimen without long-term neurotoxic sequelae or quality-of-life compromise.