Trial Information

Cognitive Functioning and Quality of Life in CNS Lymphoma

The incidence of primary central nervous system lymphoma (PCNSL) has increased threefold in
immunocompetent populations in recent years. Improvements in treatment, particularly
involving combined modality therapy with chemotherapy and radiotherapy have been shown to
augment patient survival with a median disease-free period of about 40 months. However, the
combination of these two modalities often increases the risk for delayed neurotoxicity.
There is a paucity of studies that have assessed neuropsychological functioning and quality
of life in patients with PCNSL. The majority of studies reported performance status and
survival rates, but systematic cognitive evaluations were only seldom included.
Unfortunately, relying only on these variables does not adequately assess the more subtle
cognitive impairments that most patients with brain tumors experience. Neuropsychological
difficulties often interfere with disease free patients' ability to function at premorbid
levels at work and at home. A study including neuropsychological evaluations of a relatively
large group of patients with PCNSL who received combined modality treatments, and are in
remission from their disease is planned. A follow-up assessment also will be performed in
order to monitor performance over a specified period of time. The proposed study will also
test the hypotheses that: (1) the presence of polymorphisms that influence methionine
metabolism places PCNSL patients treated with chemotherapy alone or in combination with
radiotherapy at risk for developing treatment-induced white matter disease and cognitive
dysfunction; (2) the possession of the apolipoprotein E (APOE) є-4 allele is associated with
the development of cognitive difficulties following treatment for PCNSL. Research in order
to better understand the incidence, extent, and severity of treatment-induced
neuropsychological impairments in patients with PCNSL is of utmost importance, given the
recent increase in both the number of cases diagnosed and longterm survival. It is likely to
provide valuable information regarding specific cognitive domains that should be addressed
in the development of strategies for cognitive rehabilitation or other interventions that
may be appropriate. The findings of this study will also be relevant for comparison with
ongoing and future research investigating the potential neurocognitive sequelae of
alternative treatment modalities for PCNSL (e.g., high-dose chemotherapy followed by
peripheral blood progenitor cell (PBPC) transplant).