Clinical relevance of consolidation radiotherapy and other main therapeutic issues in primary central nervous system lymphomas treated with upfront high-dose methotrexate

Purpose: To evaluate the optimal dose of methotrexate (MTX) and the efficac y of other drugs, intrathecal chemotherapy (CHT), and radiotherapy (RT) in primary brain lymphomas. Methods and Materials: Two hundred eighty-eight immunocompetent patients wi th histologically documented, previously untreated primary brain lymphomas, receiving CHT containing high-dose MTX (greater than or equal to1 g/m(2)) with or without RT were selected from 19 prospective series. The impact on survival of the MTX dose (<3 g/m(2) vs. greater than or equal to3 g/m(2)), the main drugs, intrathecal CHT, and combination CHT (mono-CHT vs. poly-CHT ) was assessed, according to the intention-to-treat principle. The role of post-CHT irradiation (immediate vs. delayed RT) was evaluated in 119 patien ts with a complete response to CHT. The whole brain and tumor bed dose (< 4 0 Gy vs. greater than or equal to 40 Gy) was assessed in 70 irradiated comp lete responders. Results: No difference in overall survival (OS) was detected between mono-C HT and combination CHT (p = 0.38). MTX greater than or equal to3 g/m(2) (P = 0.04), thiotepa (p = 0.03), and intrathecal CHT (p = 0.03) improved the O S, and nitrosoureas (p = 0.01) correlated with a worse survival. In multiva riate analysis, limited to patients receiving MTX greater than or equal to3 g/m(2), only the addition of cytarabine improved the OS; nitrosoureas redu ced MTX efficacy. Of the 119 complete responders, 70 received immediate RT. A RT dose of greater than or equal to 40 Gy to the whole brain or tumor be d did not improve OS. The 3-year OS was similar between the immediate and d elayed RT groups. In multivariate analysis, RT delay had no negative impact on survival. Conclusions: MTX greater than or equal to3 g/m(2) seems to improve survival in primary brain lymphoma patients. The efficacy of additional drugs, exce pt for cytarabine, remains unproved. Randomized trials are needed to confir m that RT withdrawal yields no detrimental effect in complete responders. ( C) 2001 Elsevier Science Inc.