HMN 2026: How Fatigue before cancer treatment is linked to adverse events

Fred Hutchinson Cancer Center-led investigators found that higher patient-reported fatigue before cancer treatment aligned with higher odds of severe, life-threatening, and fatal treatment-related toxic effects.

Fatigue and cancer

Cancer-related fatigue harms quality of life and is a persistent tiredness or exhaustion tied to cancer or cancer treatment. It interferes with usual physical and mental functioning and does not match the patient’s normal recent activity. Patients report that fatigue is among the most distressing symptoms of cancer and its treatment, yet physicians routinely underreport fatigue.

Some studies have suggested prevalence ranging from 25% to 50%. Separate estimates place moderate fatigue at 25% and severe fatigue at 15% to 20%, levels often associated with poor performance status.

In the study, “Baseline Fatigue and Severe Toxic Effects in Patients With Cancer Receiving Systemic Therapy,” published in JAMA Oncology, researchers pooled baseline fatigue data to evaluate associations between pretreatment fatigue and subsequent adverse events in cancer treatment trials.

The cohort included 7,086 patients enrolled across 17 Phase II and Phase III trials. The mean age was approximately 62, with 2,107 females (29.7%) and 4,979 males (70.3%). Cancer diagnoses included prostate, lung, colorectal, lymphoma, breast, melanoma, ovarian, and pancreatic cancer.

Cancer stages included 5,293 patients with advanced disease (74.7%) and 1,793 patients with early-stage disease (25.3%).

Baseline fatigue came from validated patient-reported outcome instruments, then mapped onto a 5-point Likert scale ranging from none to very much. Analytic models treated fatigue in multiple ways, including binary thresholds such as some or more fatigue versus less than some, plus ordinal analyses across fatigue levels.

Toxic effects rise with fatigue

Across 17 trials, 103,738 adverse events were recorded. Higher baseline fatigue aligned with higher odds of severe toxic effects. Some or greater baseline fatigue, compared with less than some fatigue, yielded an odds ratio of 2.11 for grade 3 or higher toxic effects and 1.98 for life-threatening toxic effects.

Comparison between quite a lot or very much fatigue and no baseline fatigue produced an odds ratio of 4.99 for grade 5 toxic effects.

Fatal toxic effects were uncommon, though risk rose with higher fatigue to an odds ratio of 2.35.

Severe or worse toxic effects occurred in 34.2% of patients reporting no fatigue, 39.4% reporting a little fatigue, 52.8% reporting some fatigue, and 58.3% reporting quite a lot or very much fatigue.

Subset analyses did not show statistically significant differences in the fatigue to adverse event association by age, sex, race, ethnicity, or obesity status.

Cancer stage mattered in subgroup patterns. Advanced-disease trials showed clearer monotonic relationships between baseline fatigue and adverse events, while adjuvant or early-stage trials did not show statistically significant associations for grade 3 or higher or grade 4 or higher adverse events.

What stood out

Patient-reported fatigue before cancer treatment was associated with increased risk of severe, life-threatening, and fatal adverse events during treatment.

Pre-treatment fatigue assessments could be seen as an early marker of vulnerability that could inform treatment strategies and symptom monitoring. Clinical implications point toward risk awareness at the first treatment steps.

Baseline fatigue may signal latent disease processes not captured by standard objective measures, and recognition of higher fatigue could support more careful monitoring for toxic effects during systemic therapy.

The content is provided for information purposes only.