Unequal outcomes: The role of institutional setting in the management of primary CNS lymphoma

Abstract Background: Primary central nervous system lymphoma (PCNSL) is a rare and highly aggressive non-Hodgkin lymphoma confined to the brain, spinal cord, leptomeninges, or eyes. Although potentially curable with high-dose methotrexate–based chemotherapy, real-world outcomes remain poor, with 5-year survival often under 35% (J Clin Oncol. PMID: 28640701). Delays in diagnosis or treatment, as well as limited access to specialized care, may contribute to worse outcomes (BMJ. PMID: 33148535). Academic Cancer Programs (ACPs)—including NCI-designated and university-affiliated centers—typically offer multidisciplinary teams, advanced diagnostics, and access to clinical trials (Cancer. PMID: 26218755). In contrast, Community Cancer Programs (CCPs) often have fewer resources and serve a higher proportion of socioeconomically disadvantaged patients. While institutional disparities in cancer care are well documented in other hematologic malignancies (Lancet. PMID: 34826414), their impact on PCNSL outcomes remains understudied. This study evaluates how treatment facility type and sociodemographic factors influence treatment patterns and survival in a national PCNSL cohort. Methods: We performed a retrospective cohort study of patients diagnosed with PCNSL between 2004 and 2022 using the National Cancer Database (NCDB). Patients were classified by treatment facility type: ACPs (academic/research programs including NCI-designated centers) vs. CCPs (community, comprehensive community, and integrated network cancer programs). Demographic, clinical, and treatment characteristics were compared using chi-square and Wilcoxon tests. Kaplan-Meier and Cox proportional hazards models were used to compare overall survival (OS), adjusting for age, race/ethnicity, insurance status, Charlson-Deyo comorbidity index, and distance traveled for care. Results: Of 19,947 patients with PCNSL, 12,970 (65.0%) were treated at ACPs and 5,891 (29.5%) at CCPs. Patients at CCPs were more often Hispanic (8.4% vs. 7.5%) and from rural (2.9% vs. 1.9%), low-income (28.3% vs. 25.3%), and low-education (38.5% vs. 33.0%) communities. ACPs treated more Medicaid-insured patients (7.6% vs. 5.4%) and those traveling longer distances (median 17.5 vs. 10.5 miles, p 0.001). Systemic therapy was more frequently administered at ACPs (72.8% vs. 66.9%), and fewer patients received no treatment (3.8% vs. 7.3%, p 0.001). Radiation use was higher at CCPs (23.0% vs. 18.2%, p 0.001). While median time to treatment was similar (7 days), initiation of systemic therapy occurred later at CCPs (median 19 vs. 15 days, p 0.001). Median OS was significantly longer at ACPs (19.6 vs. 10.5 months, p 0.001). Thirty- and ninety-day mortality were lower at ACPs (2.2% vs. 2.8% and 6.4% vs. 8.6%, respectively). Long-term survival remained superior at ACPs, with 2-, 5-, and 10-year OS of 38.9%, 31.0%, and 24.8%, compared to 30.6%, 24.1%, and 18.9% at CCPs (p 0.001). These differences remained statistically significant in multivariable-adjusted models. Conclusions: This large national study highlights significant disparities in the treatment and survival of patients with PCNSL based on institutional setting and socioeconomic factors. Patients treated at CCPs were more likely to experience treatment delays or omission and had significantly worse short- and long-term survival. These centers disproportionately served socioeconomically disadvantaged populations, including rural, Hispanic, and underinsured patients. In contrast, ACPs demonstrated higher treatment rates and markedly improved outcomes, despite geographic and logistical barriers. Treatment at ACPs was associated with significantly longer survival, even after adjusting for baseline characteristics. These findings underscore the critical impact of facility type on PCNSL outcomes and highlight the need for system-level interventions—such as standardized treatment protocols, improved referral pathways, and expanded tele-oncology infrastructure—to ensure equitable access to curative-intent therapy across care settings.