Patients with cancer who reported clinically significant fatigue at the start of their treatment had shorter overall survival times and more side effects than patients without fatigue. Those are the findings of a new analysis of patients who took part in four clinical trials testing treatments for lung cancer or prostate cancer conducted by the SWOG Cancer Research Network, a cancer clinical trials group funded by the National Cancer Institute (NCI).

The researchers conclude that baseline fatigue may be an important prognostic factor in oncology treatment trials. Their findings have been published in the journal JCO Oncology Practice. Initial results were previously given in a podium presentation at the 2020 American Society of Clinical Oncology (ASCO) Quality Care Symposium.

Lead author on the paper Julia Mo, BS, previously a Measey Scholar at the University of Pennsylvania and currently at the University of Rochester School of Medicine and Dentistry, notes that the study confirms that patient-reported outcome (PRO) measures indicating fatigue can be a predictor of survival in some patients with cancer. “Our findings suggest that if there is evidence of significant fatigue, patients and families should be informed and counseled on possible higher risk of poorer outcomes,” Mo says. “In addition, strategies may be developed to impact fatigue and possibly long-term outcomes.”

The authors analyzed four clinical trials: two had enrolled patients with advanced hormone-resistant prostate cancer (trials S0421 and S9916) and the other two had enrolled patients with advanced non-small cell lung cancer (trials S0027 and S9509). All participants had completed quality-of-life and symptom surveys at the start of their trial using either the Functional Assessment of Cancer Therapy (FACT) or the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire – Core 30 (EORTC QLQ-C30). Both of these survey instruments are validated measures of quality of life in patients with cancer. The researchers used the midpoint of each scale as a cutoff in categorizing whether a patient had reported a clinically significant level of fatigue before the start of treatment.

Median overall survival times for patients reporting such fatigue were approximately 26% to 45% shorter than those for patients without baseline fatigue.

The researchers also found that in the two prostate cancer studies they analyzed, patients reporting clinically significant fatigue before cancer treatment were more likely to experience severe adverse events (side effects) from chemotherapy, particularly gastrointestinal, neurological, and constitutional adverse events, although this association was not seen in the patients taking part in the two lung cancer trials.

While a number of studies have assessed how fatigue related to cancer treatment is associated with patient survival outcomes, few previous studies have investigated the relationship between pretreatment fatigue and patient morbidity and mortality outcomes.

The studies analyzed were sponsored by the NCI, part of the National Institutes of Health (NIH), led by SWOG, and conducted by the NIH-funded National Clinical Trials Network (NCTN).

The research reported on was funded by the NIH/NCI through grants CA189974, CA180888, and CA180819 and in part by The Hope Foundation for Cancer Research. Additional funding was provided by The Benjamin & Mary Siddons Measey Foundation.

The study team included Amy K. Darke, MS, Katherine A. Guthrie, PhD, and Joseph M. Unger, PhD, MS, all of the SWOG Cancer Research Network Statistics and Data Management Center, Fred Hutchinson Cancer Research Center; Jeff A. Sloan, PhD, of the Mayo Clinic; Dawn L. Hershman, MD, MS, of Columbia University Medical Center; Mark O’Rourke, MD, of the Center for Integrative Oncology and Survivorship, Greenville Health System, Clemson, SC; Marie Bakitas, DNSc, NP-C, of the School of Nursing, University of Alabama at Birmingham; and Robert S. Krouse, MD, FACS, of the Department of Surgery, Hospital of the University of Pennsylvania.

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