Study in JNCCN Identifies Significant Factors for Reducing the Risk of Immunosuppression and Fever in People Being Treated with Chemotherapy

In In The News by Barbara Jacoby

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Researchers find the timing and length of use for corticosteroids has a particularly strong impact on the likelihood of severe, life-threatening adverse events for people with cancer

New research in the October 2018 issue of JNCCN—Journal of the National Comprehensive Cancer Network identifies risk factors for chemotherapy-induced febrile neutropenia (FN) —a dangerously low white blood cell count, which increases the risk of serious infection and fever. The study was led by Chun Rebecca Chao, PhD, of the Kaiser Permanente Southern California Department of Research & Evaluation, with the intention of learning how to reduce the number of patients who experience this serious and life-threatening side effect in the future.


“Febrile neutropenia is life threatening and often requires hospitalization,” explained Dr. Chao. “Furthermore, FN can lead to chemotherapy dose delay and dose reduction, which in turn negatively impacts anti-tumor efficacy. However, it can be prevented if high-risk individuals are identified and treated prophylactically.”

The researchers studied 15,971 patients who were diagnosed with non-Hodgkin lymphoma, breast, lung, colorectal, ovarian, or gastric cancer and treated with myelosuppressive chemotherapy[1] at Kaiser Permanente Southern California between the years 2000 and 2009. Of those, 4.3% developed FN in the first chemotherapy cycle. The study’s authors found that longer term use and more recent use of corticosteroids appeared to increase the risk of FN the most, leading to three and two times the risk, respectively. Certain dermatologic and mucosal conditions (including gastritis, dermatitis, and psoriasis), as well as the use of intravenous (IV) antibiotics prior to chemotherapy were also associated with higher risk of FN during the first chemotherapy cycle.

“One way to reduce the incidence rate for FN could be to schedule prior corticosteroid use and subsequent chemotherapy with at least two weeks between them, given the magnitude of the risk increase and prevalence of this risk factor. Physicians should also consider which patients are at higher risk of FN, as identified by this study, when making decisions about using prophylactic treatment like granulocyte-colony stimulating factor (G-CSF),” said Dr. Chao.

“Identifying those at higher risk for infectious complications is a priority, in order to prevent associated complications for those undergoing treatment for cancer, especially cytotoxic therapy, as denoted in the NCCN Guidelines® for Prevention and Treatment of Cancer-Related Infections,” said Lindsey Robert Baden, MD, Dana-Farber Cancer Institute, Chair of the Panel. “In this retrospective study by Dr. Chao and colleagues, risk factors for febrile neutropenia in patients with NHL and solid tumor malignancies are assessed. Corticosteroid use and selected dermatologic and mucosal conditions are found to be associated with developing FN. It will be important for these observations to be confirmed and the time frame of risk clearly defined in order to facilitate generalizability.”

The research team was surprised to find a lack of association between prior or concurrent radiation therapy and FN, since radiation has been linked to bone marrow suppression[2]. However, they did not account for radiation field or dose, and believe more comprehensive evaluation is needed. They also found no clear association between oral antibiotic use and FN risk. The results suggest IV antibiotics may have a more profound impact on the balance of bacterial flora and other immune functions, though it is also possible that patients who received antibiotics intravenously rather than orally were generally sicker and more prone to severe infection.

To read the entire study, visit Complimentary access to “A Study of Novel Febrile Neutropenia Risk Factors Related to Bone Marrow or Immune Suppression, Barrier Function, and Bacterial Flora” is available until January 10, 2019.

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About JNCCN—Journal of the National Comprehensive Cancer Network
More than 25,000 oncologists and other cancer care professionals across the United States read JNCCN—Journal of the National Comprehensive Cancer Network. This peer-reviewed, indexed medical journal provides the latest information about best clinical practices, health services research, and translational medicine. JNCCN features updates on the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®), review articles elaborating on guidelines recommendations, health services research, and case reports highlighting molecular insights in patient care. JNCCN is published by Harborside Press. Visit To inquire if you are eligible for a FREE subscription to JNCCN, visit Follow JNCCN on Twitter @JNCCN.

About the National Comprehensive Cancer Network
The National Comprehensive Cancer Network® (NCCN®), a not-for-profit alliance of 27 leading cancer centers devoted to patient care, research, and education, is dedicated to improving the quality, effectiveness, and efficiency of cancer care so that patients can live better lives. Through the leadership and expertise of clinical professionals at NCCN Member Institutions, NCCN develops resources that present valuable information to the numerous stakeholders in the health care delivery system. As the arbiter of high-quality cancer care, NCCN promotes the importance of continuous quality improvement and recognizes the significance of creating clinical practice guidelines appropriate for use by patients, clinicians, and other health care decision-makers.

The NCCN Member Institutions are: Fred & Pamela Buffett Cancer Center, Omaha, NE; Case Comprehensive Cancer Center/University Hospitals Seidman Cancer Center and Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; City of Hope National Medical Center, Duarte, CA; Dana-Farber/Brigham and Women’s Cancer Center | Massachusetts General Hospital Cancer Center, Boston, MA; Duke Cancer Institute, Durham, NC; Fox Chase Cancer Center, Philadelphia, PA; Huntsman Cancer Institute at the University of Utah, Salt Lake City, UT; Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance, Seattle, WA; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL; Mayo Clinic Cancer Center, Phoenix/Scottsdale, AZ, Jacksonville, FL, and Rochester, MN; Memorial Sloan Kettering Cancer Center, New York, NY; Moffitt Cancer Center, Tampa, FL; The Ohio State University Comprehensive Cancer Center – James Cancer Hospital and Solove Research Institute, Columbus, OH; Roswell Park Comprehensive Cancer Center, Buffalo, NY; Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine, St. Louis, MO; St. Jude Children’s Research Hospital/The University of Tennessee Health Science Center, Memphis, TN; Stanford Cancer Institute, Stanford, CA; University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham, AL; UC San Diego Moores Cancer Center, La Jolla, CA; UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA; University of Colorado Cancer Center, Aurora, CO; University of Michigan Rogel Cancer Center, Ann Arbor, MI; The University of Texas MD Anderson Cancer Center, Houston, TX; University of Wisconsin Carbone Cancer Center, Madison, WI; Vanderbilt-Ingram Cancer Center, Nashville, TN; and Yale Cancer Center/Smilow Cancer Hospital, New Haven, CT.