The Impact of Social Determinants and Diagnostic Inequities in Hodgkin Lymphoma Outcomes: A Comparative Analysis of South America and the United States
Authors: Cantillo Garcia Ana Milena , Stemmelin German R. , Rivarola Sofía Gabriela , Enciso Arrua Maria Elvira , Von Glasenapp Seisha , Warley Fernando , Orlova Maria , Rios Jiménez Rosa Oliday , Vasquez Jule F , Quiroz Alfredo , Torres Viera Marialejandra , Castro Denisse , Irigoin Victoria , Beltran Brady E , Quintero Henry , Fernández-Águila Julio Dámaso , Oliver Ana Carolina , Castillo Jorge J. , Villela Luis Mario , Garcez Paz Diego Fernando , Valcarcel Bryan , Malpica Luis 
Published: December 2024

INTRODUCTION
Hodgkin lymphoma (HL) is a highly curable disease, with survival rates exceeding 90% in Western countries among predominantly White populations. However, clinical features and outcomes in other regions, such as South America, remain underexplored, particularly regarding the role of social determinants of health (SDOH). Understanding differences in outcomes across world regions is essential to improve outcomes globally. We conducted an exploratory international pooled analysis comparing HL subtypes and outcomes of patients with HL in South America with those in the United States (US).
METHODS
We designed a retrospective cohort study among patients aged ≥16 with newly diagnosed classical HL during 2010-2020. Patients with nodular lymphocytic HL were excluded. Data were obtained from the hospital-based registry of the Grupo de Estudio Latinoamericano de Linfoproliferativos (GELL) across 6 South American countries and the US population-based registry of the Surveillance, Epidemiology, and End Results (SEER) program. Follow-up was available through 2023 for GELL and 2021 for SEER. Patients were stratified into South American, US Hispanic, and US White groups.
Primary endpoint was overall survival (OS), defined from diagnosis to death from any cause, and estimated only among patients who received chemotherapy with or without radiotherapy. Recurrence or progression data were not available from SEER. SDOH factors evaluated were insurance status (public vs. private) and PET scan availability at the end of treatment (EOT). PET-scan availability was assessed through a landmark analysis, assuming US patients generally performed EOT PET scans as standard of care. Time-to-event endpoints were analyzed using Kaplan-Meier and multivariable Cox regression methods.
RESULTS
We enrolled 818 South American, 3,663 US Hispanic, and 11,830 US White patients. In the entire cohort, the median age at diagnosis was 38 years (range 16-91) with a male predominance (54%). Compared to US Hispanic and US White patients, South American patients had a higher frequency of mixed cellularity HL (26% vs. 19% vs. 14%; p&lt;0.001) and were diagnosed more frequently at stage III-IV disease (55% vs. 50% vs. 43%; p&lt;0.001). The proportion of classical HL not otherwise specified was lower in the South American cohort (12% vs 32-36%). Age (range 36-39 years) and male predominance (54% for all) were similar across groups. Chemotherapy with or without radiotherapy was administered to 95% of South American patients, 84% of US Hispanic patients, and 87% of US White patients. The most common chemotherapy regimen in South America was ABVD (96%). Chemotherapy approaches were not available in SEER.
With a median follow-up of 63 months among all patients that received first-line treatment with curative intent, South American patients experienced a similar OS compared to US White patients (5-year OS 86% vs. 88%; Hazard ratio [HR]=1.25, 95% confidence interval [CI]=0.98-1.60). However, US Hispanic patients had relatively worse outcomes than US White patients (5-year OS 86% vs. 88%; HR=1.44, 95% CI=1.27-1.63). Subgroup analyses of OS outcomes across demographic, HL subtypes, and cancer stage groups remained similar. In a landmark analysis, South American patients who received EOT PET-scan had comparable OS to US White patients (HR=1.40, 95% CI=0.98-1.99), but those without access to PET-scan had significantly worse outcomes (HR=2.11, 95% CI=1.49-2.98). Insurance status did not affect OS.
CONCLUSION
This study improves our understanding of the epidemiology, management, and impact of SDOH in an underrepresented region, and findings should be validated with other hospital-based or cancer registries. The higher frequency of mixed cellularity HL in South American patients provides an opportunity to investigate the role of environmental factors, such as oncoviruses (e.g., EBV or HIV), in disease etiology. The lack of EOT PET scans highlights the need to improve access to standard procedures and explore alternative methods to assess treatment responses. The comparable survival outcomes to US data underscore the importance of expanding our cohort follow-up and data collection strategies to understand better the long-term risk of treatments and the impact of SDOH on survivorship outcomes in different regions. Addressing these unmet needs is essential for improving the outcomes of patients with HL globally.