e19048 Background: The influence of duration-to-treatment interval (DTI) on outcomes in aggressive lymphoma remains uncertain. Prior studies, predominantly population-based and conducted outside the United States, have reported worse outcomes among patients with short DTI, with some demonstrating independent associations after multivariable adjustment. Other analyses emphasize heterogeneity by cohort, subtype, and health-system factors, finding no independent DTI effect. We evaluated whether DTI independently predicts overall survival (OS) in a U.S. academic single-center cohort. Methods: We analyzed 129 consecutive adults with newly diagnosed aggressive lymphoma treated at a tertiary academic center. DTI was modeled as quartiles and prespecified categories (13 days). Univariable and multivariable Cox proportional hazards models estimated hazard ratios (HR) for OS, adjusting for stage, age group, ECOG performance status, and insurance. Proportional hazards assumptions were tested; sensitivity analyses included stage-stratified models and a DTI×stage analysis. Results: Median age was 61 years (46.5% male). The most common subtype was diffuse large B-cell lymphoma (82.8%), followed by double hit lymphoma (6.2%), high grade B-cell lymphoma (6.2%), and primary mediastinal B-cell lymphoma (4.8%). Median DTI for the entire cohort was 13 days. Unadjusted analyses demonstrated a non-monotonic association between DTI quartiles and OS: Q2 (HR 0.47, 95% CI 0.22–0.99) and Q3 (HR 0.52, 95% CI 0.26–1.03) showed lower hazards versus Q1, while Q4 did not differ significantly (HR 0.82, 95% CI 0.41–1.63). The per-quartile trend lost significance after stage adjustment (HR 0.89, p=0.34). In a stage-adjusted model, DTI 7–13 versus 7 days was associated with lower mortality (HR 0.47, 95% CI 0.22–1.00, p=0.049). However, in the fully adjusted model, DTI was not independently associated with OS (7–13 vs 7: HR 0.69, p=0.39; >13 vs 7: HR 0.74, p=0.37). Stage remained the dominant predictor (HR 3.29, p=0.003). Shorter DTI groups were enriched for advanced-stage disease, while longer DTI included more early-stage cases. Insurance status was not associated with OS or PFS. Sensitivity analyses including stage-stratified models and a DTI×stage interaction did not materially change effect estimates. Conclusions: In this U.S. single-center cohort, DTI was not independently associated with OS after adjustment for disease severity and clinical covariates. Apparent adverse outcomes with shorter DTI reflected clinical triage of advanced disease rather than treatment delay. The absence of association between insurance status and outcomes is reassuring, suggesting insurance-related DTI variation did not translate into inferior survival. These findings highlight confounding in DTI analyses and support the need for larger multicenter studies with causal inference approaches.
Deng et al. (Thu,) studied this question.