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JAMA Oncol. 2019 Apr 4. doi: 10.1001/jamaoncol.2019.0086. [Epub ahead of print]

Treatment-Related Complications of Systemic Therapy and Radiotherapy.

Author information

Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut.
Cancer Outcomes, Public Policy, and Effectiveness Research Center, Yale University School of Medicine, New Haven, Connecticut.
Department of Radiation Medicine, Oregon Health and Science University-Knight Cancer Institute, Portland.
Department of Emergency Medicine, Yale University School of Medicine, New Haven, Connecticut.
National Clinician Scholars Program, Yale University School of Medicine, New Haven, Connecticut.
The James Cancer Hospital & Solove Research Institute, Division of Medical Oncology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus.
Yale Cancer Center, Yale University School of Medicine, New Haven, Connecticut.



Systemic therapy and radiotherapy can be associated with acute complications that may require emergent care. However, there are limited data characterizing complications and the financial burden of cancer therapy that are treated in emergency departments (EDs) in the United States.


To estimate the incidence of treatment-related complications of systemic therapy or radiotherapy, examine factors associated with inpatient admission, and investigate the overall financial burden.

Design, Setting, and Participants:

A retrospective analysis of the Healthcare Cost and Utilization Project Nationwide Emergency Department Sample was performed. Between January 2006 and December 2015, there was a weighted total of 1.3 billion ED visits; of these, 1.5 million were related to a complication of systemic therapy or radiotherapy for cancer. Data analysis was conducted from February 22 to December 23, 2018. External cause of injury codes, Clinical Classifications Software, International Classification of Diseases, Ninth Revision, Clinical Modification, and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10), Clinical Modification codes were used to identify patients with complications of systemic therapy or radiotherapy.

Main Outcomes and Measures:

Patterns in treatment-related complications, patient- and hospital-related factors associated with inpatient admission, and median and total charges for treatment-related complications were the main outcomes.


Of the 1.5 million ED visits included in the analysis, 53.2% of patients were female and mean age was 63.3 years. Treatment-related ED visits increased by a rate of 10.8% per year compared with 2.0% for overall ED visits. Among ED visits, 90.9% resulted in inpatient admission to the hospital and 4.9% resulted in death during hospitalization. Neutropenia (136 167 [8.9%]), sepsis (128 171 [8.4%]), and anemia (117 557 [7.7%]) were both the most common and costliest (neutropenia: $5.52 billion; sepsis: $11.21 billion; and anemia: $6.78 billion) complications diagnosed on presentation to EDs; sepsis (odds ratio [OR], 21.00; 95% CI, 14.61-30.20), pneumonia (OR, 9.73; 95% CI, 8.08-11.73), and acute kidney injury (OR, 9.60; 95% CI, 7.77-11.85) were associated with inpatient admission. Costs related to the top 10 most common complications totaled $38 billion and comprised 48% of the total financial burden of the study cohort.

Conclusions and Relevance:

Emergency department visits for complications of systemic therapy or radiotherapy increased at a 5.5-fold higher rate over 10 years compared with overall ED visits. Neutropenia, sepsis, and anemia appear to be the most common complications; sepsis, pneumonia, and acute kidney injury appear to be associated with the highest rates of inpatient admission. These complications suggest that significant charges are incurred on ED visits.

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