Is There an Indication for First Line Radiotherapy in Primary CNS Lymphoma?

SIMPLE SUMMARY: First line whole brain radiotherapy (WBRT) alone is a palliative treatment for patients with primary CNS lymphoma (PCNSL) not suitable for intensive multimodal therapy. Consolidating WBRT after chemotherapy with high-dose methotrexate WBRT has activity comparable to autologous stem cell transplantation (ASCT). However, dose-dependent toxicity of WBRT is a relevant limiting factor. With standard dose, WBRT rates of neuro-cognitive decline are high and should be taken into account. As an alternative, after complete response (CR) low-dose consolidating WBRT carries a lower risk for neurotoxicity and is a treatment option in patients not suitable for ASCT. For patients not achieving CR, the best combined treatment potentially involving focal radiotherapy remains to be determined. ABSTRACT: Background: Primary CNS Lymphoma is a rare and severe but potentially curable disease. In the last thirty years treatment has changed significantly. Survival times increased due to high-dose methotrexate-based chemotherapy. With intensive regimens involving autologous stem cell transplantation (ASCT), 4-year survival rates of more than 80% can be reached. However, this treatment regimen is not feasible in all patients, and is associated with some mortality. Methods: In this review, current evidence regarding the efficacy and toxicity of radiotherapy in PCNSL shall be summarized and discussed mainly based on data of controlled trials. Results: Being the first feasible treatment whole brain radiotherapy (WBRT) was initially used alone, and later as a consolidating treatment after high-dose methotrexate-based chemotherapy. More recently, concerns regarding activity and neurotoxicity of standard dose WBRT limited its use. On the contrary, latest evidence of some phase II trials suggests efficacy of consolidating WBRT is comparable to ASCT. After complete remission reduced dose WBRT appears as a feasible concept with decreased neurotoxicity. Evidence for use of local stereotactic radiotherapy is very limited. Conclusion: Radiotherapy has a role in the treatment of PCNSL patients not suitable to ASCT, e.g., as consolidating reduced dose WBRT after complete response. Local stereotactic radiotherapy for residual disease should be examined in future trials.