Cost of Hospitalization in Patients with Cancer and Febrile Neutropenia and Impact of Comorbid Conditions
Authors: Lyman Gary H. , Poniewierski Marek S. , Crawford Jeffrey , Dale David C. , Culakova Eva 
Published: October 2019

Background: Febrile neutropenia (FN) remains a serious complication of cancer chemotherapy often leading to hospitalization and an increased risk of mortality and cost.
Methods: Data on hospitalizations between 2004 and 2012 at US academic medical centers and their affiliated hospitals reporting to the University Health Consortium were utilized. The analysis included admissions of adult patients (age ≥18 years) with lymphoma or solid tumors and neutropenia. For patients with multiple admissions, the first hospitalization during the time period studied was selected. Cancer diagnosis, presence of neutropenia, comorbidities, and infectious complications were based on ICD-9-CM codes. The primary outcome of the analysis was total cost of hospitalization. All cost estimates were adjusted for inflation and converted to 2014 US dollars. Length of stay (LOS) and mortality were studied as secondary outcomes. A multivariable linear regression model was used to evaluate the association of demographic and clinical factors with the total cost. Both total cost and LOS were log-transformed in the model.
Results: Among 3.3 million hospitalizations of adult patients with solid tumors or lymphoma from 239 medical institutions, there were 108,807 admissions with neutropenia in 86,611 individual patients including 29% with lymphoma, 13% gastrointestinal cancer, 13% lung cancer, 10% breast cancer, and 35% with other solid tumors. Nearly one-quarter (24%) were between 50-59 years of age and an additional 27% of patients were 60-69 years old. Major comorbid diseases were present in 70% of patients with 25,923 (30%), 19,636 (23%), and 15,005 (17%) having 1, 2, or ≥3 major medical comorbidities, respectively. Median (mean) LOS was 5 (8.6) days with a quarter of patients hospitalized >10 days and 17% requiring the intensive care unit (ICU) stay. Average cost per day and total cost of hospitalization were $2,556 and $22,126, respectively. For patients who required ICU care, considerably higher total cost (mean: $51,745 vs. $15,953), cost per day (mean: $3,598 vs. $2,075), and length of hospitalization (mean: 15.8 vs. 7.1 days) were observed compared to patients without ICU stay. Hospitalization costs were greater in patients with lymphoma (mean=$29,853) compared to solid tumors (mean=$18,883) where the mean cost ranged from $11,337 in patients with breast cancer to $28,581 in those with brain tumors. Hospitalization costs increased in patients with major comorbidities with the highest mean costs for venous thromboembolism ($43,660), cerebrovascular disease ($43,273) and hepatic disease ($42,441) with mean lengths of stay of 15.6, 14.8, and 13.2 days, respectively. Regardless of tumor type, presence of multiple comorbidities further increased cost. Infectious complications associated with greatest mean costs were sepsis ($45,861), IV line infection ($45,021), pneumonia ($40,438), and fungal infections ($36,203). While changes in average LOS over time were small (mean 8.3 and 8.6 days in 2004 and 2012, respectively), the average cost of hospitalization, adjusted for inflation, rose from $18,815 in 2004 to $23,352 in 2012. In-hospital mortality was observed in 6.9% of patients overall with annual mortality rates varying between a minimum of 6.4% and maximum of 7.5% remaining relatively stable over time (6.8% in 2004, 6.4% in 2012). After adjusting for age, ethnicity, cancer type and LOS in the multivariable model, multiple comorbidities, infection, and year of hospitalization remained significantly associated with increased total cost.
Conclusions: FN represents an oncologic emergency often requiring hospitalization and is associated with considerable mortality and costs. Major drivers of hospitalization costs include type of malignancy, number of major comorbidities and infectious complications. While lengths of stay and mortality rates have remained relatively constant, costs of hospitalization with cancer and neutropenia have risen over the past decade, considerably outpacing the rate of inflation.

Disclosures
Lyman: Amgen: Research Funding. Crawford:Aggenix: Consultancy; Amgen: Consultancy, Research Funding; Bayer: Consultancy; Boehringer Ingelheim: Consultancy; Eli Lilly: Consultancy; Gilead: Consultancy; Hospira: Consultancy; Ono Pharmaceutical: Consultancy; Astra Zeneca: Research Funding; GTx: Research Funding; Med Immune: Research Funding; Morphotek: Research Funding. Dale:Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau.