Abstract

Primary central nervous system lymphoma (PCNSL) is an aggressive neoplasm with a poor prognosis. Early studies of whole brain radiation therapy (WBRT) alone revealed a robust initial response but high rates of local recurrence with long-term follow-up. The addition of high-dose methotrexate (HDMTX)-based chemotherapy improved the durability of disease control. However, delayed neurotoxicity emerged as an important complication, mainly in elderly patients. Therefore, researchers have investigated eliminating WBRT or reducing its dose. Multiple studies of chemotherapy alone have demonstrated inferior disease control. On the other hand, a phase III trial reported that WBRT may be deferred until relapse without compromising survival; however, this trial is fraught with flaws. A recent study of immunochemotherapy and dose-reduced WBRT demonstrated excellent outcomes. Currently, this regimen is being studied in a multi-institutional trial by the Radiation Therapy Oncology Group. WBRT maintains an important position in the armamentarium against PCNSL. This article aims to describe its evolving role.