Publication Only: Aggressive non-Hodgkin lymphoma - Clinical
Primary central nervous system lymphoma (PCNSL) is a rare malignancy with a median survival of less than 3 months, if untreated. Multimodality treatments with high-dose methotrexate (HD-MTX)-based systemic therapy and/or whole brain irradiation for consolidation or salvage constitutes the most commonly used treatment approach. Due to severe treatment toxicity and aggressive course of the disease, not all patients benefit from this treatment approach.
In this retrospective study, we aimed to identify various clinical parameters that predicted outcomes on survival, and response to various treatments in patients with PCNSL.
Patients diagnosed with PCNSL between 2002 and 2017 were selected for analysis. Data on patient demographics, tumor characteristics and treatment were collected and analyzed for correlation with clinical outcomes. Survival curves were generated with the Kaplan-Meier method and compared using log-rank test. Multivariate analysis was performed where prognostic variables and patient outcome were correlated with Cox proportional hazard model.
A total of 82 patients were identified and selected for analysis. Median age at diagnosis was 68 years (range 30-89 years) and median follow up was 3.7 years. The majority (86.6%) of tumors were identified as diffuse large B-cell lymphoma on histology. Among the 82 patients, 10 (12.2%), 31 (37.8%) and 23 (28.0%) patients received systemic therapy (CT) only, radiotherapy (RT) only and systemic therapy followed by salvage radiotherapy (CRT), respectively, while 18 (22.0%) patients received supportive care (SC) only. Median time interval between diagnosis and treatment was 33 days for CT group and 63 days for RT group. Median overall survival (OS) of the entire cohort was 11.1 months (95% CI 6.1-15.5 months), while median OS for RT, CRT and SC groups were 8.8 months (95% CI 4.5-11.3 months), 30.1 months (95% CI 19.3-41.0 months) and 3.3 months (95% CI 0.8-5.8 months), respectively (median OS for CT group not reached). Multivariate analysis demonstrated that both the use of systemic therapy (hazard ratio [HR] 0.23, 95% CI 0.11-0.49, p < 0.001) and radiotherapy (HR 0.54, 95% CI 0.32-0.92, p = 0.022) were associated with improved survival in the total population, while age (p = 0.48) or type of tumor (p = 0.88) did not demonstrate any statistical significance. Subgroup analysis showed that systemic therapy in patients younger than 70 years of age was associated with improved OS (HR 0.13, 95% CI 0.05-0.32, p < 0.001), whereas in elderly patient population (70 years of age or older), addition of radiotherapy was associated with improved OS (HR 0.45, 95% CI 0.21-0.96, p = 0.039).
Our results concur with the published literature demonstrating the survival benefit with the use of systemic therapy in younger patient population. Radiotherapy was independently associated with an improved overall survival in older patient population and therefore should be considered as palliative treatment of choice in the elderly population who may not be candidates for systemic therapy. Further prospective studies are required to validate our findings as well as optimization of radiotherapy in this population.