Twenty-five years survival of primary central nervous system lymphomas treated with the C5R regimen

Very long-term survival has seldom been reported in primary central nervous system lymphoma (PCNSL) We report the updated outcome of patients treated in the C5R protocol from 1982 to 2001 in the Centre Leon Berard with a median follow-up of 35 years.

This retrospective analysis included the 43 patients treated within the C5R protocol combining HDMTX ARA-C and alkylating agents, with a consolidation with 20 Gys whole brain radiotherapy (WBRT) and a 30Gys boost. The first cohort includes the 25 patients of the initial C5R publication; the second cohort includes all subsequent 18 patients treated with C5R until 2001 in trials. Information on survival, relapse, second cancers, and post treatment leukoencephalopathy were collected.

Thirty-nine deaths are documented. Median OS and PFS are 7.0 years (95%CI:1.9-12.1) and 4.7 years (95%CI: 0.33-9.01) respectively. Three patients are alive disease-free at 27, 28, and 44 years after treatment, 2 retired, 1 professionally active. While no prospective neurocognitive assessment was conducted, 14 patients presented neurocognitive deterioration for a projected incidence of 60% at 20 years. Second primary cancers were reported in 6 patients for a projected incidence of 28% at 20 years. The causes of death were PCNSL, neurotoxicity, and second cancers in 24 (55.8%), 5 (11.6%) and 5 (11.6%) of patients respectively, with 4 (9,3%) deaths during treatment and 1 (2.3%) of unknown cause.

Very long-term survivors are observed in PCNSL treated 25-44 years ago. Late relapses, late neurocognitive decline and second cancers are common and important causes of deaths.