Determining barriers to access first-line treatment in high volume facilities in adolescents and young adults (AYA) with acute leukemias

Abstract Adolescents and young adults (AYA) with acute leukemias, including acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL), face substantial challenges in receiving optimal healthcare, with disparities in outcomes impacted by race, ethnicity, and socioeconomic status. While treatment in high-volume centers has been associated with improved survival outcomes, the specific challenges that hinder AYA patients from obtaining this care and the effects on time to treatment and survival have not been thoroughly examined. Investigating these barriers is critical to enhancing health equity and optimizing outcomes for this population. Therefore, we aimed to investigate patient factors, including patient demographics and social determinants of health, that influence access to definitive treatment at high- vs low-volume facilities among AYA with acute leukemias. We also aimed to determine factors that predict time from diagnosis to definitive treatment (≥8 days) and overall survival (OS) based on facility volume. A retrospective analysis was conducted using the National Cancer Data Base (NCDB) for AYA patients (18-39 y/o) with newly diagnosed acute leukemias (AML, B-cell ALL and T-cell ALL) between 2010-2021, with at least one year of follow-up, who received first line definitive treatment at the reporting facility. Since facility type in the NCDB is censored for AYA, facility volume was used as a surrogate measure. Facilities were stratified into quartiles by case volume; high-volume facilities were defined as top two quartiles and the bottom two as low-volume. The primary outcome was treatment delay, defined as ≥8 days from diagnosis to initiation of therapy based on prior literature linking earlier initiation with improved survival (Genc, et al, 2023 Oncol Ther ). OS was measured from diagnosis to death, with censoring at last contact. Patient demographics, socioeconomic factors, and facility volume were compared using chi-square tests. Logistic regression assessed factors influencing treatment delays and Cox proportional hazards models for OS. Statistical significance was set at p <0.05. We identified 5,029 AYA patients with acute leukemias, of which 58.4% were treated at high-volume facilities and 41.6% at low-volume facilities. Older age (22-39 y/o), Hispanic ethnicity, and lack of insurance were more common among patients at low-volume facilities (p <0.05). Patients at low-volume centers had higher odds of treatment delay (OR 1.36, p<0.001) and worse survival (HR=1.22, p<0.001). Longer distance to center was associated with treatment at high-volume facilities (80.9% ≥100 miles vs 47% for <10 miles, p<0.001) and fewer treatment delays (11.4% vs 17.5%, p=0.006). Receiving chemotherapy at the reporting facility was protective against delay (OR 0.29, p<.001). Older patients (HR ≈ 1.5, p <0.001), Black race (HR=1.26, p=0.009), and government or no insurance (HR ~1.3, p <0.05) were associated with higher mortality. The survival benefit with high volume care was more pronounced in ALL than AML (High vs Low HR, ALL 0.77, AML 0.99, p=0.0347). In this national retrospective review, first line definitive treatment at low-volume centers was associated with both treatment delays and worse survival outcomes in AYA patients with acute leukemia compared to those who received care at high-volume facilities within <8 days. Race, insurance status, and socioeconomic factors continue to contribute to disparities in treatment access and OS. Treatment delays at low-volume centers are likely multifactorial, driven by referral processes, resource limitations, diagnostic delays and institutional workflows. These findings show opportunities to improve early referral pathways to high-volume centers and reduce care fragmentation to mitigate delays and improve outcomes.