Whole Brain Radiotherapy and Ara-C In Consolidation Post High-Dose Methotrexate Is Important In Establishing Durable Disease Control In the Treatment of Primary CNS Lymphoma: A Single Centre Observational Study

Abstract 1776

While the survival benefits of high-dose methotrexate (MTX) based chemotherapy for primary central nervous system lymphoma (PCNSL) are well documented, the place for adjunctive cytarabine, and whole brain radiotherapy (WBRT) in consolidation remains uncertain. Due to the potential significant risk of treatment delayed neurotoxicity, the delivery of WBRT is often omitted at the physician's discretion in the treatment of PCNSL, especially in elderly patients. In the absence of randomised control trials comparing survival outcomes between patients receiving high dose MTX with or without WBRT in consolidation, we performed a retrospective study assessing the impact of these treatment modalities and other prognostic factors on the overall survival in a heterogeneously treated population with PCNSL.

Forty-five patients with newly diagnosed PCNSL were identified at Monash Medical Centre, Australia between 1995 and 2009. Twenty patients were treated with palliative intent and were removed from analysis. The remaining 25 patients had a median age of 59 (range 31–79). Twenty-four patients had diffuse large B cell lymphoma, one T-cell lymphoma. Positive CSF cytology for lymphoma was found in 4 patients. All actively treated patients received chemotherapy; 16 patients received high-dose MTX-based combination chemotherapy, 5 patients received single-agent high-dose MTX, and 3 other. Eleven patients (median age 48, range 31–79) received WBRT in consolidation. The median dose of RT delivered was 39.6 Gy (range 20–45 Gy).

After a median follow up of 2.1 years (range 0.3 – 11.6 years), the 5 year PFS was 27% and 5 year OS was 40% for all patients in the actively treated group. On univariate analysis, Age <60 years at diagnosis was significantly associated with both increased in PFS (p=0.002) and OS (p=0.04). Patients who received WBRT in consolidation tended to have a longer PFS (5 year PFS 49% vs. 12% p=0.098) compared to patients who did not receive WBRT. However, OS in both groups were similar (5 year OS 47% (consolidation WBRT) vs. 42%, p=0.31). Importantly, no relapses were observed in patients receiving WBRT who survived 2.7 years. Although formal neuropsychiatric assessment was not performed, examination of the records identified no significant cognitive impairment in survivors. Adjunctive cytarabine was associated with improved OS (p<0.001), however use of cytarabine was correlated with age<60 (Fishers exact test). Nonetheless, on multivariate analysis, the use of cytarabine was the only covariate associated with improved PFS and OS (p<0.001, Cox regression).

Conclusion. The potential of cure in a proportion of patients as a result of initial therapy is suggested in this single centre experience by the plateau in the PFS and OS curve. This study underscores the potential role of both WBRT and AraC in consolidation after high dose MTX-based chemotherapy, in establishing durable disease control, and supports such an approach particularly in young patients with good performance status. The lack of overt neurotoxicity associated with moderate dose radiotherapy is of particular interest; although long-term formal cognitive assessments are lacking in this case.