Sex-and-ethnicity-related differences in primary central nervous system lymphoma based on the SEER database

Abstract BACKGROUND Primary central nervous system lymphoma (PCNSL) is a rare and aggressive form of Non-Hodgkin Lymphoma. Typically, PCNSL are of the Diffuse Large B-cell Lymphoma (DLBCL) histologic subtype, and despite rarely spreading out of the CNS, the prognosis is poor. In the literature, prior reports have deeply analyzed the influence of age in the prognosis of PCNSL, but large population-based studies on the influence of sex and ethnicity remain scarce. The main objective was to define sex-and-ethnic-related differences in overall survival among PCNSL patients and to develop a risk calculator that allows clinicians to establish individual prognostic. METHODS In this retrospective cohort study using the SEER 17 Registry from the Nov 2024 submission, we identified 5 643 patients diagnosed with PCNSL from 2000-2022. Patients with unknown ethnicity (n=28) were excluded from race-stratified analyses. Overall survival (OS) was computed using Kaplan-Meier curves with log-rank tests stratified by sex (male vs female) and ethnicity (Non-Hispanic White (NHW), Non-Hispanic Black (NHB), Hispanic, Asian/Pacific Islander (API)). Multivariable Cox proportional hazards models were fitted for age, sex, ethnicity, stage of PCNSL, histologic subtype, surgery, chemotherapy and radiation. Model performance was assessed by concordance index (C-index) using internal cross-validation. We then built a risk calculator using Shiny (RStudio) to compute individualized 1-3-5 year survival predictions based on the parameters of the best performing model. RESULTS 5 615 patients were included (49% male, median age: 62 years). Median OS for the overall cohort was 18 months. By race, median OS was 16 months for white patients (NHW), 11 months for black patients (NHB), 27 months for Hispanic, and 29 months for Asian patients (API) (p<0.001). Female patients showed a trend toward longer survival compared with males (median OS 20 vs. 16 months, p=0.06) In multivariate analysis, male sex was associated with higher mortality (HR 1.16, 95% CI 1.08-1.23, p<0.001). Compared to NHW patients, Hispanic (HR 0.82, 95% CI 0.73-0.91, p<0.001) and API (HR 0.75, 95% CI 0.67-0.85, p<0.001) ethnic-backgrounds had lower hazard of death, while NHB was associated with higher risk (HR 1.22, 95% CI 1.10-1.36, p<0.001). We compared multiple prognostic models via internal cross-validation: a standard Cox model (C-index 0.704), a splined-age Cox model (0.710), a Cox model with an age-surgery interaction (0.712), a LASSO-penalized Cox model (0.684), and a Random Forest model (0.690). Risk calculator tool for PCNSL was built and fitted according to the Cox model with age-surgery interaction as it achieved the highest performance. CONCLUSION Sex and ethnicity are independent prognostic factors in PCNSL. Male patients and NHB patients had poorer survival, while Hispanic and API patients fare better. Standard therapeutic regiments (chemotherapy, surgery and radiation) remain strong protective interventions to prolong survival. Our PCNSL risk calculator is accessible and allows personalized prognostication.