TOPLINE:

In an analysis of 17 clinical trials, patients reporting fatigue prior to systemic cancer treatment faced double the risk for severe toxic effects and nearly five times the risk for fatal complications compared with those with minimal to no fatigue.

METHODOLOGY:

• Fatigue is a common, often debilitating, symptom in patients with cancer. However, the prevalence of fatigue prior to treatment, and its relationship with patients’ risk for treatment side effects, have received little research attention.
• Researchers analyzed data from 17 SWOG Cancer Research Network clinical trials conducted between 1990 and 2022. Together, they involved 7086 patients (mean age, 62 years; 29.7% female) with prostate, lung, colorectal, lymphoma, breast, melanoma, ovarian, or pancreatic cancer.
• Each trial collected information on patients’ baseline fatigue, and those measures were mapped onto a five-point Likert scale ranging from “no fatigue/none” to “very much.”
• The primary outcomes were grade 3-5 adverse events. To account for confounding, the analysis was clustered by trial and adjusted for age, sex, race, and obesity.

TAKEAWAY:

• At baseline, 2771 patients (39.1%) reported at least “some” fatigue. Overall, 44.1% of patients had adverse events of grade 3 or higher (severe), while 14.1% had toxicities of grade 4 or higher (life-threatening), and 0.9% had fatal complications.
• Compared with patients reporting little to no baseline fatigue, those reporting at least some fatigue had increased risks for severe toxicities (odds ratio [OR], 2.11; P < .001) as well as life-threatening (OR, 1.98; P < .001) or fatal (OR, 2.35; P = .03) toxicities.
• In multivariable regression models, a dose-response pattern emerged, with patients reporting “quite a lot” or “very much” fatigue having a fivefold higher risk for fatal toxic effects (OR, 4.99; P = .002).
• Adverse event patterns differed between advanced disease and adjuvant trials. There was a more pronounced association between baseline fatigue and treatment toxicity in advanced disease trials, in terms of grade 3 or higher events (OR, 1.51 vs 0.96; P for interaction = .003) and grade 4 or higher (OR, 1.49 vs 0.79; P for interaction = .006).

IN PRACTICE:

The findings suggest that “ in this era of precision medicine, patient-reported fatigue may be an important component of determining risk of toxic effects and could aid in risk-mitigation strategies and treatment decision-making,” the authors of the study wrote. They noted that the underpinnings of the association are unclear, since cancer-related fatigue is complex, but fatigue may serve as a general marker of biological vulnerability.

SOURCE:

This study, led by Joseph M. Unger, PhD, Fred Hutchinson Cancer Center in Seattle, was published online in JAMA Oncology.

LIMITATIONS:

The heterogeneity of the included trials could have resulted in confounding by factors not incorporated into the statistical model. The findings may not be fully generalizable to patients in clinical settings, partly due to the exclusion of sicker patients from clinical trials.

DISCLOSURES:

The research was supported by grants from the US National Institutes of Health, the National Cancer Institute, and the National Clinical Trials Network, as well as the Hope Foundation for Cancer Research. Some authors disclosed having financial relationships with commercial sources outside the submitted work.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.