Clinical features, central nervous system risk, and therapeutic outcomes in primary sinonasal diffuse large B-cell lymphoma: a retrospective cohort study of 94 patients

Background: Primary sinonasal diffuse large B-cell lymphoma (PSN-DLBCL) is a rare extranodal malignancy accounting for approximately 1-2% of all lymphomas. Its clinical course, optimal treatment strategy, and the patterns and risk of central nervous system (CNS) involvement and relapse remain incompletely characterized. We therefore conducted a retrospective cohort study of treatment-naïve patients with PSN-DLBCL to describe clinicopathologic features, treatment patterns, and prognosis, and to explore the incidence and presentation of CNS involvement and relapse; given the retrospective study design and limited events, analyses are exploratory and hypothesis-generating rather than conclusive. Methods: We enrolled 94 treatment-naïve patients with histologically confirmed PSN-DLBCL treated between 2009 and 2024. Baseline evaluation included positron emission tomography/computed tomography (PET/CT) and magnetic resonance imaging (MRI) examination. Treatment involved rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP), dose adjusted rituximab, etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (da-R-EPOCH), or polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin, prednisone (Pola-R-CHP) regimens. CNS prophylaxis included intrathecal chemotherapy and/or high-dose methotrexate (HD-MTX). Survival analysis was performed using the Kaplan-Meier method with log-rank testing. Prognostic factors were assessed by univariate and multivariate Cox proportional hazards regression. Landmark analyses were used to evaluate the impact of interim and end-of-treatment responses on survival. Results: The median age was 68.5 years; 61.7% had limited-stage disease. Baseline CNS involvement was identified in 9 patients (9.6%). Estimated 5-year progression-free survival (PFS) and overall survival (OS) rates were 67.0% and 73.1%. Survival did not differ significantly by treatment regimen or primary site. High International Prognostic Index (IPI) score was independently associated with inferior OS [hazard ratio (HR) =3.11; 95% confidence interval (CI): 1.26-7.68] and PFS (HR =2.51; 95% CI: 1.06-5.96) on multivariate analysis, and radiotherapy demonstrated a trend toward improved PFS. CNS relapse occurred in only 2 patients (2.1%), and CNS prophylaxis with HD-MTX or intrathecal chemotherapy showed no significant association with improved survival in this cohort. Achievement of complete response (CR) at interim and end-of-treatment evaluations was associated with significantly improved PFS and OS on landmark analysis. Conclusions: PSN-DLBCL shows favorable long-term outcomes with immunochemotherapy. Despite relatively frequent baseline CNS involvement, CNS relapse was rare. Local invasion might represent the main pathway for CNS involvement. Substituting intrathecal therapy for systemic HD-MTX is not recommended. The benefit of CNS prophylaxis was not evident in our cohort. High IPI score and failure to achieve CR were the primary adverse prognostic factors. These findings provide substantive real-world evidence and highlight the need for prospective studies to refine management strategies.