Naqvi, Tahir

e20595 Background: Circadian regulation of immune function has been proposed as a modifier of immune checkpoint inhibitor (ICI) efficacy, with retrospective studies suggesting improved outcomes with earlier infusion timing. Whether these findings translate to routine oncology practice, where ICIs are administered across multiple lines, frequently combined with chemotherapy, and subject to treatment interruptions, remains uncertain. We evaluated the association between ICI infusion timing and overall survival (OS) in a real-world cohort of patients with non-small cell lung cancer (NSCLC). Methods: A retrospective cohort study included adults with NSCLC who received at least one line of ICI therapy at a community oncology center between January 2018 and December 2024. Infusion timing was defined at the patient level as morning-only ( < 1300 hours), evening-only (≥1300 hours), or mixed timing, reflecting receipt of infusions exclusively in different time-of-day categories across treatment lines. OS was measured from diagnosis to death or last follow-up. Kaplan-Meier and Cox proportional hazards models were used. Multivariable analyses adjusted for stage, ECOG performance status, body mass index, and premature ICI discontinuation. Line of therapy was excluded due to collinearity with mixed-timing classification and risk of immortal time bias. Results: A total of 127 patients were included (morning-only n = 77; mixed timing n = 36; evening-only n = 14). Staging data were available for 99.2%, and 94 deaths occurred. Median OS was 495 days for morning-only, 850 days for mixed timing, and 388 days for evening-only patients. Kaplan-Meier analysis showed no statistically significant OS differences across groups. In sensitivity analysis excluding patients with mixed infusion timing, morning-only and evening-only groups demonstrated overlapping survival curves, with no evidence of a time-of-day–specific survival advantage. In univariate analysis, mixed timing was associated with a borderline reduction in mortality compared with morning-only infusions (HR 0.63, 95% CI 0.39-1.00), while evening-only timing was not (HR 1.63, 95% CI 0.85-3.16). In multivariate analysis restricted to stage III-IV disease, infusion timing was not independently associated with OS. ECOG performance status, premature ICI discontinuation and advanced staging were the strongest predictors of mortality. Conclusions: In this real-world NSCLC cohort, ICI infusion timing was not independently associated with overall survival after adjustment for patient fitness and treatment continuity. These findings suggest that in pragmatic settings, clinical factors may outweigh subtle chronotherapy effects reported in more selected populations.

e16586 Background: Guideline-discordant care disproportionately affects racial minorities, uninsured, and underinsured patients, yet prior studies lack quantification of absolute survival time lost. We evaluated equity-adjusted survival penalties from non-adherence to guideline-concordant therapy in muscle-invasive bladder cancer (MIBC). Methods: From the National Cancer Database, we identified patients with non metastatic muscle invasive bladder cancer (cT2 to T4a, N0 or N1, M0). Overall survival was defined from diagnosis to death or last contact. Guideline-concordant therapy was defined as radical cystectomy (± perioperative systemic therapy) or trimodality therapy (definitive bladder radiotherapy with chemotherapy); all other patterns were classified as discordant. Of 55,873 eligible patients, 28,025 received concordant therapy (27,401 cystectomy; 524 trimodality therapy) and 27,848 received discordant careInverse probability of treatment weighting (IPTW) was used to balance demographic, socioeconomic, facility, tumor, and temporal covariates. We analyzed survival using weighted Kaplan-Meier and Cox models censored at 36 and 60 months. Equity-adjusted survival penalties were calculated as the difference between observed survival and counterfactual survival predicted from concordant-only models. Restricted mean survival time losses were extrapolated to years lost per 1,000 patients. Results: Guideline concordance was associated with significantly improved survival (36-month HR 0.64; 60-month HR 0.68; both p < 0.01). Among concordant modalities, radical cystectomy conferred an early survival advantage over trimodality therapy at 36 months (HR 0.23; p < 0.05) which dissipated by 60 months (HR 0.53; p > 0.05). Survival penalties were most severe for vulnerable populations. At 36 months, uninsured patients incurred a 0.90-month survival penalty (75.0 life-years lost per 1,000 patients). By 60 months, penalties widened: uninsured patients lost 1.94 months (161.7 life-years/1,000), Filipino patients lost 1.53 months (127.0/1,000), Medicaid beneficiaries lost 0.97 months (80.8/1,000), and patients at community cancer programs lost 0.21 months (54.1/1,000). Conclusions: In this national cohort of 55,873 patients, guideline concordance reduced the propensity-weighted risk of death by 32% to 36% at 3 and 5 years. However, non-adherence results in substantial absolute survival losses for marginalized groups. By quantifying these "survival penalties," we demonstrate that targeting the factors underlying discordance offers a direct opportunity to reduce inequities and achieve measurable population-level survival gains in MIBC.