The Endothelial Activation and Stress Index (EASIX) at diagnosis is associated with survival in primary central...

Primary central nervous system lymphoma (PCNSL) has poor outcomes despite high-dose methotrexate-based therapy. The Endothelial Activation and Stress Index (EASIX) is associated with prognosis in systemic lymphomas but has not been evaluated in PCNSL. Define the association of baseline EASIX in multivariate analysis with Memorial Sloan Kettering Cancer Center (MSKCC) score risk factors. A multicentre retrospective cohort included 128 immunocompetent adults with biopsy-proven diffuse large B-cell PCNSL. EASIX was calculated and the optimal cut-off (0.751) was determined by receiver operating characteristic (ROC) analysis. The primary end-points were overall survival (OS) and progression-free survival (PFS) in the low-EASIX and high-EASIX groups. The median age was 60 years. High EASIX (≥0.751, n = 55) was associated with Eastern Cooperative Oncology Group (ECOG) ≥2 (p = 0.002), elevated lactate dehydrogenase (LDH) (p < 0.001), deep brain lesions (p = 0.007) and cellular myelocytomatosis oncogene/B-cell lymphoma-2 (MYC/BCL-2) double expression (p = 0.01). After a median follow-up of 37 months, high EASIX was associated with inferior OS (27.4 months vs. not reached; p = 0.001) and PFS (25.6 months vs. not reached; p < 0.001). Multivariable Cox analysis confirmed high EASIX as an independent adverse factor for OS (hazard ratio [HR] 4.75) and PFS (HR 4.99), with additional prognostic discrimination within MSKCC risk groups. Baseline EASIX could potentially improve risk stratification and prognostic modelling in PCNSL.