Treatment of Primary CNS Lymphoma in the Elderly, a Multicenter Retrospective Analysis

Patients with primary CNS lymphoma (PCNSL) are preferably treated with high-dose Methotrexate (HD-MTX)-based chemotherapy followed by consolidation radiotherapy in many centers. As elderly patients have an increased risk of complications with this approach, they are frequently treated with chemotherapy or radiotherapy alone. Little is known about the efficacy and toxicity of either of these treatments in elderly patients outside clinical studies. We analysed all patients aged 60 or above referred with PCNSL to 5 Dutch centers between 1998 and 2007. 110 patients were identified. We excluded: patients who were not treated because of a poor condition (n=25), patients with EBVrelated NHL (n=3), patients with PCNSL confined to the eyes (n=3), and patients with missing information on follow-up (n=5). The remaining 74 patients had a median age of 65 years (range 60–82), and a median KPS of 70% (range 30–100). Twenty-nine of them were treated with radiotherapy only, 19 with chemotherapy only and 26 with both; 19 of these 26 received radiotherapy after failure of chemotherapy. Median KPS was 70 in both single treatment modality groups and 80 in the group receiving both modalities. The response rate (CR or PR) was 69% (20/29) in patients treated with radiotherapy only and 63% (12/19) in patients treated with chemotherapy only. Timing of both response evaluation and radiotherapy after chemotherapy were highly variable in the group treated with both modalities, therefore these patients are only included in the overall survival analyses. Median overall survival (OS) was 20 months: 7 months for patients treated with radiotherapy only, 23 months for those treated with chemotherapy only, and 31 months for combined modality treatment (p=0.01). The KPS was a significant prognostic factor for as well PFS as OS (p<0.001): median PFS and OS were 3 and 4 months respectively in patients with KPS < 70 and 18 and 25 months in patients with a KPS ≥ 70. Forty of the 45 patients receiving chemotherapy were planned for treatment with a MTX dose of 3g/m². There were 2 toxic deaths. Ten of the 40 patients received delayed or reduced doses, or aborted chemotherapy because of toxicity. Delayed encephalopathy was reported in 15 patients: 7/30 patients after radiotherapy, 1/19 after chemotherapy only and 7/26 after combined treatment. Five died as a consequence of the encephalopathy.

Conclusion: Performance status is the most important single variable determining prognosis in elderly patients. Overall survival after HD-MTX-based treatment for PCNSL in the elderly appears to approach survival obtained in younger patients, provided the performance status is adequate. Treatment related mortality of HD-MTX-based chemotherapy seems not to be increased in older patients.