Primary central nervous system lymphoma (PCNSL) is a rare variant of non-Hodgkin's lymphoma that is increasing in incidence. Methotrexate-based chemotherapy in combination with whole-brain radiotherapy (WBRT) has dramatically improved the outcome of patients. However, treatment-related neurotoxicity is a significant complication, especially after radiotherapy in the elderly. Despite advances in therapy, several important questions remain regarding optimal methotrexate dose, dosing frequency, adjunct chemotherapy, and the impact of deferring WBRT. Advances in biologic therapy and strategies to intensify the delivery of chemotherapy may help to limit the use of radiotherapy, thus lessening potential neurotoxicity. Studies looking at oncogenic proteins as potential prognostic markers for PCNSL may help us to develop risk-adapted therapies.
