Disparities in survival outcomes among adolescent and young adults vs adult populations with Hodgkin lymphoma: A population based SEER study

Abstract Introduction Hodgkin lymphoma (HL) outcomes have improved markedly over recent decades, yet population-based data on overall survival (OS) across age, demographic, and treatment-delay subgroups remain limited. We leveraged the Surveillance, Epidemiology, and End Results (SEER) database to describe real world OS and quantify the impact of age, sex, race/ethnicity, rurality, primary site, and time to treatment initiation (TTI) on survival in a large United States cohort. Methods We queried SEER Research Data across 17 Registries spanning from 2000-2022 to identify 32,483 patients aged ≥15 years with a first primary HL (nodal or extranodal). Patient variables included age (AYA 15–39, MidAge 40–59, Older ≥60), sex, race (White, Black, Asian/Pacific Islander [API], American Indian/Alaska Native [AI/AN]), Hispanic origin, rural–urban continuum code, primary site, year of diagnosis, and TTI (days from diagnosis to first therapy). To reduce confounding biases, it was made sure that only those patients are included which have a single primary malignancy i.e HL. We calculated descriptive statistics and median (IQR) TTI by age group. Median follow-up among survivors was 107.0 months (IQR 48.0–176.0). OS was estimated by Kaplan–Meier (KM) with log-rank tests. Multivariable Cox proportional hazards (PH) models included all covariates; PH assumptions were tested via Schoenfeld residuals. For covariates violating PH, we fitted an extended Cox model with interactions between log(time) and age and TTI. A landmark analysis examined conditional OS beyond 60 months. Five-year OS estimates were derived from KM curves. Results Of 32,483 patients, median age was 35 years (IQR 25–50); 57.8% were AYAs, 25.2% MidAge, and 17.0% Older. Males comprised 54.1%; 81.2% were White, 12.5% Black, 5.8% API, and 0.5% AI/AN; 17.8% were Hispanic; 61.2% resided in large metropolitan counties. Primary nodal HL accounted for 97.9%. Median TTI was 15 days (IQR 0–32) in AYAs, 21 days (0–39) in MidAge, and 22 days (0–43) in Older (p<0.05). Five-year OS was 85.5% overall. By KM, 5-year OS was approximately 88% in AYAs versus 75% in MidAge and 46% in Older (p<0.05); no unadjusted difference by Hispanic origin (p=0.073); significant differences by race (p<0.05) and rurality (p<0.05); and superior OS in nodal versus extranodal HL (p<0.05). In the base Cox model, adjusted hazard ratios (HRs) for OS were: MidAge versus AYA 2.91 (95% CI 2.80–3.03), Older versus AYA 13.45 (12.61–14.34), Male versus Female 1.30 (1.22–1.38); compared to AI/AN, API 0.48 (0.35–0.66), Black 0.68 (0.53–0.88), White 0.45 (0.33–0.61); Hispanic versus Non-Hispanic 1.34 (1.25–1.44); nodal versus extranodal 0.80 (0.70–0.92); and per-year of diagnosis 0.95 (0.94–0.96). TTI did not have a constant effect (HR per day 1.00, p=0.32); extended modeling confirmed significant time-dependent effects of age and TTI (p<0.05). In landmark analysis beyond 60 months, conditional 5-year OS remained >90% in AYAs, ~85% in MidAge, but continued to decline in Older patients (p<0.05). Conclusion In this SEER cohort of HL, younger patients, females, API and White patients, and those with nodal disease had markedly better OS. While TTI had no uniform effect, its impact varied over time. These findings establish benchmarks for modern HL outcomes and underscore persistent disparities by age, sex, race, and rurality. Further work should explore interventions to mitigate these gaps.