Improved survival with combined chemo-radiotherapy in primary central nervous system lymphoma

Background: Primary CNS lymphoma (PCNSL) is an aggressive primary brain tumor. Cranial irradiation alone rarely results in long term disease control or prolonged survival. We retrospectively analyzed data on the effect of adding high-dose methotrexate (HDMTX) prior to whole brain irradiation (WBI). Methods: All patients with PCNSL diagnosed and managed during 1991-2004 were identified and demo-graphic characteristics, prognostic factors, treatment and outcome were reviewed. Of 62 patients, 10 were ex-cluded (4 had WBI <40 Gy and 6 had no treatment). Radiation alone was considered curative with a dose >40 Gy. Combined modality therapy included 3-4 cycles of HDMTX (3 g/m2) followed by WBI. result: Of 52 patients analyzed for outcome, 36 had WBI (dose >40 Gy), 16 received 3-4 cycles of HDMTX followed by WBI (combined modality therapy [CMT]). Median age was 48.2 years; 42 years in the CMT group, 51 years in WBI. Patient characteristics were comparable between two groups except for higher multifocal tumor in the CMT group (92% vs. ×22%, P=.029). Median follow up was 12.83±6.4 months. The hazard ra-tio for an event was 0.64 (95% CI, 0.52-0.98) and for death 0.58 (95% CI, 0.48-0.92), both in favor of CMT. Univariate regression analysis using one-way analyses of variance (ANOVA) and multivariate Cox regression analysis for prognostic factors including age (<60 vs. >60), ECOG PS (0-2 vs. 3-4), extent of surgery (biopsy vs. debulking), solitary vs mutifocal tumor and dose of radiation therapy (<50Gy vs. >50Gy) failed to identify any prognostic factor. conclusion: This retrospective comparison supports phase II trial results that indicate that high-dose metho-trexate followed by WBI in PCNSL improves outcome.