Identifying multi-level social determinants for disparities in survival and patient-reported outcomes in national head and neck cancer trials.

11066 Background: This study aimed to determine to what extent area-level social determinants of health (SDOH) interact with individual, institutional, and biological factors to predict outcomes in head and neck cancer (HNC) trials. Methods: Five NRG Oncology HNC trials (2635 patients receiving chemoradiation) were analyzed. Area-level SDOH coded by patient ZIP codes included rurality (rural-urban commuting area code), neighborhood socioeconomic deprivation (Area Deprivation Index [ADI] categorized as upper vs. lower quartile), and travel burden (distance and time to treatment site). Individual (demographic, cancer and treatment-related factors), institutional (accrual volume), biological (HPV+/-) factors, and outcomes (overall survival [OS], progression free survival [PFS], quality of life [QOL], and symptoms) were analyzed. Multivariable Cox proportional hazards regression and mediation analysis using logistic regression assessed associations using hazard ratio (HR) or odds ratios (OR) and 95% confidence intervals (CI). Results: Most patients were White (88%), non-Hispanic (92.7%), of mean age of 57 years, HPV+ (64.6%), and received intensity-modulated radiotherapy (95.9%) and cisplatin (94.2%). ADI and rurality were not associated with OS and PFS. OS and PFS were higher in patients with travel time <1 hour (HR=0.85, 95% CI [0.75, 0.98]; HR=0.85, 95% CI [0.73, 0.98]) and travel distance <50 miles (HR=0.84, 95% CI [0.72, 0.96]; HR=0.85, 95% CI [0.73, 0.98]). ADI, travel time, and travel distance were not associated with QOL decline. Patients treated at institutions with high rural accrual volume had worse QOL decline from baseline (OR=0.36, 95% CI [0.15, 0.85]). The impact of travel distance but not time varied by race to influence QOL decline (OR=0.38, 95% CI [0.16, 0.93]). ADI was not associated with symptoms, but patients from institutions with high rural accrual volume had worse symptoms (OR=7.83, 95% CI [1.98, 31.01]). HPV status had a significant indirect effect on the relationship between travel distance and survival at 1 year (estimate [β]=0.03, 95% CI [0.01, 0.05]) and 5 years (β=0.03, 95% CI [0.004, 0.05]), as well as a direct and total mediation effect of travel distance on QOL decline at 1 year (direct β=-0.08, 95% CI [-0.16, -0.004]; total β=-0.89, 95% CI [-0.17, -0.01]). Conclusions: This study showed the impact of area-level SDOH and their interactions with race and institutional accrual volume, which are associated with survival, QOL, and symptom changes. HPV status potentially mediated the effects of travel distance on outcomes. Our findings provide novel approaches to identify patients at risk for poor outcomes, such as those with travel burden at institutions with high rural accrual, to design community-based interventions to improve cancer outcomes.