Academic cancer programs deliver improved long-term survival in nodular lymphocyte predominant Hodgkin lymphoma: Insights from 7,000+ United States patients

Abstract

Abstract Background Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a rare subtype of Hodgkin lymphoma (HL), accounting for only 5% of HL cases (Hematol Oncol PMID: 40517549). It typically presents with an indolent course and excellent overall survival, although approximately 10% of cases may transform into aggressive large B-cell lymphoma (Luek Lymphoma PMID: 39743924). The disease predominates in males (~75%) and has a median age of diagnosis of 40 years (Luek Lymphoma PMID: 39743924). Treatment varies by stage, ranging from radiotherapy alone in stage IA to chemotherapy and anti-CD20 therapy in advanced cases. To our knowledge, this study represents the first large-scale retrospective analysis using the National Cancer Database (NCDB) to compare sociodemographic factors, clinical features, and survival outcomes among patients with NLPHL treated at Academic Cancer Programs (ACPs) versus Community Cancer Programs (CCPs). Methods We conducted a retrospective analysis of patients diagnosed with NLPHL in the United States between 2004 and 2022 using the National Cancer Database. Demographic, clinical, and survival data were compared between patients treated at ACPs and CCPs. ACPs included academic and research programs, including NCI-designated comprehensive cancer centers. CCPs comprised community, comprehensive community, and integrated network cancer programs. Kaplan-Meier and Cox proportional hazards models were used to compare overall survival (OS), adjusting for age, race/ethnicity, insurance status, comorbidity score (Charlson-Deyo), and distance from treating facility. Results Of 7,012 patients with NLPHL, 37% were known to be treated at an ACP and 29% at a CCP. A majority of patients treated at both ACPs and CCPs were male (60%). The median age at diagnosis was slightly younger for ACPs (56 years) compared to CCP (57 years) (p<0.001). The majority of patients at both ACPs (60%) and CCP (57%) were diagnosed at <60 years of age. A slightly higher proportion of patients aged ≥75 were treated at ACPs (9.3% vs. 8.1%; p<0.001). White patients were diagnosed at a higher rate (76%) in CCPs as compared to ACPs (70%). Black patients were more frequently treated at ACPs (25% vs. 20%), while white patients predominated in both settings (70% ACPs, 76% CCPs). The majority of patients were non-Hispanic. Private insurance was the most common among both groups—ACPs (58%) and CCPs (57%)—followed by Medicare (27% vs. 31%; p<0.001). Analysis of socioeconomic factors using census median income data from 2016 to 2020 revealed that median household income >$74,063 was most common across both groups (34% ACPs, 33% CCPs). Rural residence was more frequent in CCPs (2.5%) compared to ACPs (1.2%). Median distance to treatment facility was slightly longer for ACPs (10 miles) vs. CCPs (9 miles). Most patients had a Charlson-Deyo score of 0 (80% ACP, 79% CCP), though ACPs had more scores ≥2 (7% vs. 6%; p<0.001). Stage I was the most common at diagnosis (33% ACPs, 36% CCPs), followed by Stage II (28% both). Median time to treatment initiation was similar between groups—36 days (ACPs) and 35 days (CCPs). Two-, five-, and ten-year overall survival (OS) rates were higher in ACPs-treated patients: 96% vs. 93%, 90% vs. 87%, and 81% vs. 77%, respectively. Cox regression confirmed significantly better OS in ACPs patients after adjustment for covariates (p<0.0001). Conclusions This study demonstrates a statistically significant OS advantage for patients with NLPHL treated at ACPs compared to CCPs, despite similar age at diagnosis and early-stage presentation. Notable differences included a higher proportion of Black patients treated at ACPs and a greater proportion of rural patients treated at CCPs. Interestingly, ACP patients had slightly more comorbid conditions, yet still experienced improved survival outcomes. Although NLPHL generally carries an excellent prognosis, these findings underscore that treatment at ACPs may confer additional survival benefits. This advantage may be attributed to increased access to multidisciplinary care, specialized expertise, and advanced diagnostic and therapeutic resources, which are particularly important in the management of rare lymphomas such as NLPHL. These results are consistent with previous studies showing improved outcomes for patients treated in academic settings and highlight the continued need to understand and address disparities in cancer care delivery.