Longer Distance to a Specialized Treatment Center Does Not Adversely Affect Access to Treatment or Outcome in Acute Myeloid Leukemia: A National Population-Based Cohort Study
Authors: Tostesen Michael Buch , Norgaard Jan M. , Nørgaard Mette , Medeiros Bruno C. , Marcher Claus Werenberg , Overgaard Ulrik Malthe , Schöllkopf Claudia , Severinsen Marianne Tang , Oestgaard Lene Sofie Granfeldt 
Published: October 2019

Abstract
BACKGROUND
Treatment of acute myeloid leukemia (AML) is widely centralized at specialized centers. Longer distances to a specialized treatment facility may affect patients' access to curative-intended treatment and ultimately survival. Few studies have focused on the potential distance decay association in hematological cancers and limitations include small sample size and lack of individual-level socioeconomic, clinical, and treatment information.
AIM
We designed a large national population-based cohort study of all AML patients diagnosed in Denmark between 2000-2014 (followup ending 2017) to investigate the effect of distance on treatment intensity and outcome considering individual-level clinical and socioeconomic factors.
METHODS
Demographics, clinical, and outcome data were obtained from the Danish National Acute Leukemia Registry (DNLR). Socioeconomic information was retrieved from registries at Statistics Denmark (Figure 1).
Distance to specialized treatment centres was calculated using shortest route (Google Maps) from city center of habitation and categorized into groups.
We investigated effects of distance to nearest specialized treatment center on chance of receiving intensive chemotherapy using logistic regression analysis (odds ratios; ORs). In intensive therapy patients, we calculated chance of complete remission (CR [ORs]) and in allogeneic transplantation (HSCT) candidates; we estimated chance of HSCT (ORs). Overall survival was calculated for all patients and in intensive therapy patients only using cox regression (Hazard Ratios; HRs).
All results were adjusted for sex, age, and individual-level socioeconomic (ethnicity, income, education, and occupation) and disease-related factors (WBC, secondary or therapy-related AML, cytogenetics, performance status, and comorbidity). Results were given crude and adjusted with 95% confidence intervals (CI), and stratified by age (<65 years; ≥65 years).
RESULTS
Of 2992 patients (median age 68.5 years), 53% received intensive chemotherapy, and 71% (n=1045) achieved a CR. The median distance to a specialized treatment center was 40 km (interquartile range 10-77 km). Patients living furthest from a specialized center had lower income and lower educational level.
No negative impact of distance to specialized treatment center was seen on chance of receiving intensive therapy (adjusted ORs: <10 km 1.0, 10-25 km 1.10 (CI=0.69-1.73), 25-50 km 1.10 (CI=0.73-1.66), 50-100 km 1.33 (CI=0.90-1.97), and >100 km aOR 1.40 (CI=0.90-2.16)).
In intensive therapy patients (n=1588), distance to specialized treatment center did not affect time from diagnosis to chemotherapy initiation or chance of achieving a CR.
In HSCT candidates (866 patients ≤70 years with non-favorable cytogenetics achieving CR), longer distance to transplant center was not negatively associated with chance of HSCT (adjusted ORs: distance<50 km 1.0, 50-200 km 1,27 (CI=0.56-2.90), and >200 km 0.77 (CI=0.34-1.74)).
The median follow up time was 514.5 days. Figure 2 shows crude survival by distance to specialized treatment center overall and in selected subgroups. Overall survival was not affected by distance to specialized treatment center (adjusted HRs: distance <10 km 1.0, 10-25 km 0.98 (CI=0.84-1.16), 25-50 km 1.01 (CI=0.88-1.18), 50-100 km 1.01 (CI=0.88-1.16), and >100 km 0.99 (CI=0.85-1.16)). Similar results were found in intensive patients only.
Stratifying by age or analyzing distance as a continuous variable did not change the overall interpretation of results.
CONCLUSION
In a population-based national setting, distance to specialized treatment facilities offering remission-induction chemotherapy and HSCT, does not affect access to care, treatment outcome, or survival in AML patients. These findings support that the current centralization of specialized treatment does not negatively affects AML outcomes in a universal health-care system.

Disclosures
No relevant conflicts of interest to declare.