Baseline fatigue linked to worse toxicity from cancer treatments

medwireNews: Among people with cancer, the presence of fatigue before starting treatment is associated with an increased risk for severe, life-threatening, or fatal adverse events (AEs), suggests a pooled analysis.

“Fatigue assessments at treatment initiation may serve as an early clinical marker of risk for toxic effects and may help inform personalized treatment strategies and symptom monitoring,” say Joseph Unger (Fred Hutchinson Cancer Center, Seattle, Washington, USA) and co-researchers in JAMA Oncology.

The team analyzed data from 17 SWOG Cancer Research Network phase 2 and 3 clinical trials conducted between 1990 and 2022 in which patients had been evaluated for fatigue prior to beginning the protocol therapy.

The analysis comprised 7086 patients aged an average of 61.1 years, the majority (70.3%) of whom were men due to the inclusion of five prostate cancer trials. Three of the trials involved people with lung cancer, two each with breast and colorectal cancer, and lymphoma, and one each with melanoma and pancreatic and ovarian cancer.

As different questionnaires were used to evaluate fatigue across the trials, the researchers mapped the fatigue item from each to a 5-point Likert scale going from no fatigue (0) to a little (1), some (2), quite a lot (3), and very much (4) fatigue. Based on this, 39.1% of patients reported some or greater fatigue at baseline, while 16.4% reported quite a lot or very much fatigue.

In all, 103,738 AEs were reported across the trials, with 44.1% of participants experiencing an AE of at least grade 3 (severe), 14.1% of at least grade 4 (life threatening), and 0.9% of grade 5 (fatal).

Those who reported at least some baseline fatigue were significantly more likely than their counterparts who reported a little or no fatigue to experience AEs of grade 3 or worse, grade 4 or worse, or of grade 5, at odds ratios of 2.11, 1.98, and 2.35, respectively.

And there was a dose–response relationship, with the likelihood of each category of AEs rising with increasing fatigue levels. Indeed, patients who reported quite a lot or very much fatigue at baseline had a fivefold increased risk for grade 5 AEs versus those with no fatigue.

The researchers say that although the biologic underpinnings of this relationship are not totally understood, “the capacity of patient-reported fatigue to predict future symptomatic and objective consequences of cancer treatment suggests fatigue may be a practical and useful marker for extant underlying disease processes.”

They continue: “If so, then interventions to address existing fatigue symptoms in patients with cancer may reduce symptoms of this debilitating condition and, potentially, any limited direct effects on treatment toxic effects.”

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2026 Springer Healthcare Ltd, part of Springer Nature

JAMA Oncol 2025; doi:10.1001/jamaoncol.2025.5549