Impact of Primary Site and Histologic Subtype in Hepatobiliary and Pancreatic Lymphomas on Patient Outcomes: Analysis of SEER Database

Introduction Primary hepatobiliary and pancreatic lymphomas (PHBPL) are an extremely rare and aggressive subset of lymphomas representing <0.5% of pancreatic cancers and 1% of extranodal lymphomas. There is paucity of data regarding this rare tumor subset, its clinicopathological features as well as the optimal therapy and outcomes. We sought to explore patient outcomes of PHBPL compared to primary nodal disease utilizing the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database. Methods We used the SEER database to extract demographic and disease data on patients diagnosed with lymphoma from 2010-2015. Primary disease site was classified into three categories: primary hepatic lymphoma (including biliary tract, gallbladder, liver), primary pancreatic lymphoma (including ampulla of Vater), and primary nodal lymphoma (lymph nodes and spleen). Ann Arbor stage I and stage II were grouped as early-stage disease, while stages III and IV were grouped as late-stage. Patient cases were also divided into three distinct groups based on the histologic subtype: aggressive NHL (DLBCL, Burkitt lymphoma, MCL, T-cell lymphoma), indolent NHL (FL, marginal zone lymphoma), and Hodgkin's lymphoma. Summary statistics were used to analyze demographic and disease data. Our main outcome of interest was overall survival defined as time in months from diagnosis to death from any cause. Cox-proportional hazards models and Kaplan-Meier method were used to perform univariate analysis. Multivariate analysis was also performed to control for factors such as age, Ann Arbor stage, race, and income. Primary nodal lymphoma served as the comparison group for both univariate and multivariate analysis. Statistical significance was defined using a 95% confidence interval and a p-value < 0.05. Results A total of 55,115 cases were included in the final analysis. The most common primary disease site was primary nodal lymphoma (54,454 cases, 98.8%) followed by primary hepatic lymphoma (435 cases, 0.79%) and primary pancreatic lymphoma (226 cases, 0.41%). The median age at diagnosis was 63 years old with majority of patients identifying as male and Caucasian (56.26% and 70.4% respectively). Late stage lymphoma represented 62.69% of the cohort while early stage lymphoma represented 37.31%. Primary hepatic lymphoma was associated with worse overall survival when compared to nodal lymphoma (HR = 2.077, p < 0.0001). This finding remained statistically significant even after controlling for age, race, income, and stage (HR = 1.836, p < 0.0001). Primary pancreatic lymphoma was also associated with worse overall survival (HR = 1.226, p = 0.0349). This association persisted on multivariate analysis though statistical significance was not met (HR= 1.1182, P = 0.0841). Conclusions In this analysis of a large national cancer database, hepatic and pancreatic lymphomas have respectively significantly and slightly worse outcomes than their nodal counterparts. This association persisted on multivariate analysis, though multivariate findings for primary pancreatic lymphoma did not meet statistical significance. These results warrant validation in future prospective studies including studies that use risk adapted approach to guide therapeutic decisions.