Update on the Management of Primary CNS Lymphoma

In their well-written update on the management of primary central nervous system (CNS) lymphoma, Drs. Nasir and DeAngelis of Memorial Sloan-Kettering Cancer Center (MSKCC) combine extensive personal experience with a timely, critical review of the pertinent literature to provide readers with a well-balanced view of the current management of the patient with primary CNS lymphoma. The initial diagnosis and evaluation of a patient with primary CNS lymphoma is truly a multidisciplinary effort involving the neurosurgeon, hematopathologist, neurologist, ophthalmologist, hematologist, and radiation therapist. This team must act quickly and smoothly to initiate therapy as soon as possible, before the onset of additional neurologic disability. Drs. Nasir and DeAngelis provide helpful, practical suggestions for the diagnosis and staging of patients with this disease; these suggestions are succinctly summarized in the tables that accompany the article. The authors appropriately offer a cautionary note regarding corticosteroid use prior to biopsy that will be useful to clinicians outside of major centers when they encounter this uncommon tumor. In the section on treatment, the authors review the major studies of radiation therapy alone, combined chemotherapy and radiotherapy, and chemotherapy alone. They conclude that the conventional chemotherapy programs used for systemic large-cell non-Hodgkin’s lymphoma (NHL)—eg, cyclophosphamide, doxorubicin HCl, Oncovin, and prednisone (CHOP)—are not effective for primary CNS lymphoma. The authors suggest that a chemotherapy program that includes high-dose methotrexate and/or cytarabine produces optimal survival. Avoiding Neurocognitive Defects The authors are appropriately circumspect regarding the neurocognitive impact of previous and current therapies. The ability of a regimen to achieve a complete tumor response and long-term survival must be balanced against the toxicity of the regimen, especially its long-term neurocognitive defects. Careful analyses of the experiences of the Oregon group[1] as well as our own[2] suggest that, given sufficient follow-up, these regimens may be shifting the time to disease progression, and perhaps altering the patterns of progression, without increasing the number of cured patients, or certainly the number of cured patients with preserved functionality. Treating Patients With Non-AIDS Primary CNS Lymphoma Is the experience with primary CNS lymphoma at MSKCC typical of the patient with non–acquired immunodeficiency syndrome (AIDS) primary CNS lymphoma who is seen in the community? There are some suggestions that it may not be, as indicated by the following two examples. First, the incidence of cerebrospinal fluid (CSF) involvement among MSKCC patients has always been greater than that recorded at other institutions, including our own. The paper by Balmaceda and colleagues[3] cited by Drs. Nasir and DeAngelis provides convincing data that confirm the MSKCC experience. However, is the difference between these data and those from other institutions due to better cytologic preparation and analysis, a longer time from symptom onset to diagnosis and CSF sampling, or a biologically different group of patients? Certainly, these latter two possibilities might also convey a statistical advantage to any administered therapy, independent of its antineoplastic effect.[4] In fact, the authors quote reviews by Corry et al[5] and Blay et al[6] suggesting that CSF involvement may impart a survival advantage. Second, the survival and time to progression in the MSKCC experience are similar to those in other single-institution studies,[7] but differ from the experiences of our group and others. The Radiation Therapy Oncology Group (RTOG) is testing the MSKCC regimen in a phase II setting. These results should provide data for comparison with the North American and European studies that the authors cite in their article.