The treatment and outcomes for primary CNS lymphoma improved in the 1990s with the incorporation of high-dose methotrexate-based regimens. These gains were in part offset by neurotoxicity associated with the use of whole brain radiation therapy (WBRT), usually manifest as impaired cognitive function or overt dementia. Gavrilovic and colleagues now update the extensive Memorial Sloan-Kettering Cancer Center experience with follow-up of a consecutive non-randomized series of 57 patients treated from 1992-98 with high-dose methotrexate (MTX), procarbazine, vincristine, cytarabine, and intrathecal MTX (per Ommaya reservoir). WBRT 45 Gy was also included, although after 1995 patients > 60 years of age did not receive RT due to recognition of neurotoxicity being pronounced in this age group. Overall, 17 patients (30 percent) remain alive at the time of analysis (December 2005), 13 of whom were < 60 years at the time of initial therapy (Table).
In Brief
Primary CNS lymphoma remains a significant clinical challenge. While it occurs with increased frequency among individuals with congenital or acquired immunodeficiency, it also occurs in those who are immunologically intact. Spread outside the CNS is unusual, although ocular, spinal cord, and leptomeningeal involvement may occur. As demonstrated in this long-term follow-up study, improved outcomes as compared with historical experience were realized using a combined modality regimen incorporating high-dose methotrexate and WBRT, albeit at the cost of neurotoxicity and neurocognitive decline, especially in patients > 60 years of age. The authors note that they likely underestimated the rate of neurotoxicity, as formal neuropsychiatric testing was not performed. WBRT is now deferred in many patients, especially in the older age group. Future studies will need to incorporate cognitive testing and utilize recently developed standardized staging and response criteria1 . Newer therapeutic strategies include the use of rituximab and temazolamide, which have activity in recurrent disease; these agents have been incorporated into up-front therapy ongoing trials. Recent reports have also suggested benefit for stem cell transplantation as part of initial therapy in younger patients.
