Facility-level differences in treatment and outcomes for intravascular large B-cell lymphoma: A national cancer database analysis

Abstract

Abstract Background: Intravascular large B-cell lymphoma (IVLBCL) is a rare and aggressive subtype of extranodal diffuse large B-cell lymphoma, characterized by the growth of lymphoma cells within the vessel lumen of various organs. The lack of significant lymphadenopathy and the disease's clinical heterogeneity often hinder timely and accurate diagnosis, with approximately half of reported cases identified only at autopsy (Lancet Oncol. PMID: 19717091). Given its rarity, population-level data are limited. Understanding real-world patterns of diagnosis and treatment is critical to improving outcomes in this elusive malignancy. This study explores demographic, clinical, and treatment features between patients treated at academic cancer programs (ACPs) versus community cancer programs (CCPs) and evaluates their impact on survival outcomes. Methods: We conducted a retrospective analysis of 305 patients diagnosed with IVLBCL between 2010 and 2022 using the National Cancer Database (NCDB). Patients were stratified by facility type: ACPs included academic and research programs, including NCI-designated centers, while CCPs encompassed community, comprehensive community, and integrated network cancer programs. Demographic, clinical, and treatment variables were compared across cohorts. Kaplan-Meier analysis and Cox proportional hazards models were used to estimate overall survival (OS), adjusting for age, race/ethnicity, insurance status, Charlson-Deyo comorbidity score, and distance from the treating facility. Patients with unknown or missing facility type were excluded from comparative analysis. Results: Among 305 patients, 229 (75.1%) were treated at ACPs and 72 (23.6%) at CCPs. Median age was lower in ACPs (66 vs. 69 years, p<0.001). Patients treated at ACPs were more likely to have private insurance (34.1% vs. 18.1%) and reside in higher-education ZIP codes, while those at CCPs were more often from Medicaid non-expansion states (37.5% vs. 28.4%, p<0.001). There were no significant differences in race/ethnicity or urban/rural residence. Time to chemotherapy initiation was significantly shorter at ACPs (median 9 vs. 18.5 days, p=0.005). Overall treatment rates were similar (~85%), and most patients in both groups presented with advanced-stage (Stage IV) disease at diagnosis. Comorbidity burden was generally low: most patients had a Charlson-Deyo score of 0 (75.4% ACP vs. 70.8% CCP), with no significant difference in higher scores (≥2: 4.0% vs. 5.6%, p = 0.67). Median crowfly distance to the treating facility was slightly greater at ACPs (11.2 miles vs. 8.5 miles, p = 0.041), reflecting broader regional referral patterns. No differences were noted in facility-level treatment capabilities (e.g., radiation use or transplant eligibility) based on facility type. Median OS was longer in ACPs vs. CCPs (24.8 vs. 20.4 months), though not statistically significant (p=0.496). Notably, early survival favored CCPs: 2-year OS was 58.4% vs. 51.1%, and 5-year OS was 46.8% vs. 44.9%, also not statistically significant (p=0.52). On multivariable analysis, age ≥70 years and Charlson-Deyo score ≥2 were associated with inferior OS, while facility type was not independently predictive of survival (p = 0.76). Kaplan-Meier curves showed overlapping confidence intervals throughout follow-up. Conclusions: This is the largest NCDB study to date examining facility-level disparities in patients with intravascular large B-cell lymphoma. Patients treated at ACPs were generally younger, more likely to have private insurance, and initiated chemotherapy more quickly compared to those at CCPs. Despite these differences in access and treatment timelines, both early and long-term survival outcomes were similar between groups. These findings suggest that when appropriate therapy is delivered, high-quality outcomes can be achieved in both academic and community settings. While these observations must be interpreted cautiously given the absence of statistically significant survival differences, they underscore the importance of standardizing care protocols and enhancing access to timely treatment. Further prospective and molecularly annotated studies are needed to validate these findings, elucidate biological contributors to prognosis, and inform future therapeutic strategies for this ultra-rare lymphoma subtype.