Treatment of Primary CNS Lymphoma in the Elderly with High-Dose Methotrexate Containing Chemotherapy Followed Radiotherapy or Chemotherapy Alone Plus Deferred Radiotherapy: Evaluation of Modification of Treatment Modalities in Leon Berard Cancer Center

• Published in: Blood 2009-11, Vol.114 (22), p.2702-2702
• Main Authors: Ghesquières, Hervé, Bajard, Agathe, Albrand, Gilles, Alaoui-Slimani, Khaoula, Rey, Philippe, Sebban, Catherine, Sunyack, Marie Pierre, Jouanneau, Emmanuel, Ducray, Francois, Chassagne-Clement, Catherine, Biron, Pierre, Blay, Jean-Yves
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V114.22.2702.2702

Abstract 2702 Poster Board II-678 Treatment of Primary CNS lymphoma (PCNSL) is based on high-dose methotrexate (HD-MTX) and cytarabine containing chemotherapy (CT) followed by brain radiotherapy (RT). However, the risk of leukoencephalopathy (LE) is important after chemoradiotherapy, especially for patients older than 60 years old. To reduce neurotoxicity in clinical practice, RT is restricted at relapse or for not responding patients after CT, but no formal randomized trial had evaluated this two modalities of treatment. The objective of this study is to evaluate this modification of clinical practice in our institution over time. 74 patients older than 60, median age 68 years old (range, 60–81) were treated in our institution between 1986 and 2008. Before 2003, 51 patients were treated with HD-MTX CT followed by RT. Most patients (59%) were treated with HD-MTX + CHOP-like with intermediate dose of MTX (1.5g/m2) and only 25% received 3g/m2 of MTX per course. Evaluation of this schedule in the prospective phase II GELA trial LNHCP93 showed excessive rate of toxic death during CT. Since 2004, 23 patients were treated with expected less toxic protocol and increased dose of MTX (3g/m2, 83% of patients), and RT was omitted for patients in complete response (CR) in order to limit risk of LE. Acute toxicity, initial response, risk of relapse, overall survival (OS) and risk of neurotoxicity were compared between these two periods. As acute treatment toxicity had a powerful impact for these categories of patients especially for patients treated in first period, we access if hazard ratio (HR) was constant over time by determining Schoenfeld residuals. A piecewise Cox proportional model was used in defining time periods after visual inspection of Schoenfeld residuals. Strategy (CT+RT vs.CT only) was tested during each time period in order to detect a difference on survival. Comparison of clinical characteristics showed that patients in second period were slightly older (71 vs. 67, p=0.008) but Performance Status, LDH level, rate of involvement of deep structures of brain, CSF protein level, leptomeningeal involvement were not different between the 2 cohorts. Toxic death rate during treatment was significantly more important in first period (31% vs. 9% p=0.04). CR after CT was significantly better for patients treated after 2003 (33% vs. 48% p=0.01), but was similar at the end of treatment, CT + RT (49%) vs. CT strategy (48%). The follow-up of cohort 1 and 2 was 95 a