Cancer-related fatigue (CRF) is a persistent, subjective sense of tiredness related to cancer and treatment that interferes with usual functioning. Other features of CRF include tiredness that is not relieved by rest or sleep, is often associated with physical and psychological symptoms, can be acute or chronic, and may not correspond to a patient’s level of exacerbation.

Joachim Voss, PhD, RN, ACRN, FAAN, from Case Western Reserve University, discussed CRF and how the understanding of genomic sequencing and biomarkers can help improve patient care and outcomes during a session at the 42nd Annual Congress in Denver, CO.

CRF is the most common symptom that adult patients with cancer experience, and it can be caused by all types of cancer treatments. It is characterized by impaired physical, cognitive, and social function; exhaustion; apathy; and social withdrawal. The true prevalence of CRF is unknown because of variables, but estimates fall between 15% and 99% of patients, with the majority of studies putting CRF occurrence in more than 50% of cancer cases. In addition, 30% of all patients with breast cancer will stay fatigued 5– 10 years after treatment, according to Voss.

CRF is multifactorial and causes can include the cancer itself, treatment, pain, anemia, fatigue prior to treatment, other medical condition, lack of physical activity, nutrition issues, medications, emotional distress, and sleep problems. Voss gave examples of the multifactorial process of CRF, including that patients can have nausea from treatment, which leads to a decreased appetite and poor dietary intake, which results in a nutritional imbalance and, ultimately, fatigue. “If you feel lousy, you are not going to the gym, eating well, or sleeping well,” he said. “Wellness behaviors have to be relearned throughout the journey of being diagnosed, treated, and living as a patient with cancer and then a survivor.”

“Tumors are incredible energy hogs,” Voss said, noting that treatment on top of that requires more of patients’ energy.

Practitioners should encourage an incremental approach to increasing energy levels and activities of daily living. “When we recommend an exercise regimen, that is overwhelming,” he said. “Start with, ‘Did you get out of the house today?’ or ‘Did you make it to the mailbox?’”

Patients may also face stress from family members of caregivers who can become frustrated and see the fatigue as being lazy. “Fatigue is hard to see and touch,” Voss cautioned.

Voss then discussed how biomarkers may serve as a role in offering better care for CRF. Biopsychosocial models have shown the intricate interrelationships between biology, behavior, thought, experience, social interactions, and health. This technology could provide connections between measurable and identifiable biomarkers and symptoms and lead to innovative new clinical and research directions that promote an understanding of this previously unmeasurable phenomenon.

Many studies are looking for a biologic basis for fatigue, looking at inflammation, metabolic and neuroendocrine function, and genetics (see Table 1). “We know that these factors are related to musculoskeletal dysfunction, sleep disturbance, depression, cognitive disturbance, poor nutrition, and poor functional status,” Voss said. Biomarkers could potentially contribute to a more complete understanding of the mechanisms that cause CRF, predicting patients at the highest risk for severe fatigue, and determining who to tailor interventions to based on objective measures that are predictive of fatigue trajectory. Cutting-edge biomarkers will include imaging, epigenetics, proteins (post-translation modifications of proteins), and metabolomics.

He noted that nurses “have to be brave and move our science and interest forward. There is lots to be done in terms of the standards to classify patients and help them early on to have a much more successful trajectory through cancer treatment. This is what I would call precision nursing.”

Voss looked to the future in how CRF biomarker research could guide better understanding and measurement of symptom science. “CRF biomarkers have the potential to transform practice and patient education,” he said, noting four ways this can happen:

  • Susceptibility, risk, and prediction
    • Patients with specific genetic markers diagnosed with cancer at the highest risk for CRF will receive early intervention.
  • Diagnosis and prognosis
    • Specific markers indicate the presence and potential trajectory can influence care planning.
  • Monitoring
    • As biomarker changes occur, practitioners can anticipate changes in CRF and quantify the impact of intervention efficacy.
  • Pharmacodynamic and response biomarker
    • Help understand the relationship between specific treatments and fatigue.

“I am a nurse; I care most about practice,” Voss concluded.

Voss, J. (2017). Up close and personal with fatigue biomarkers. Session presented at the ONS 42nd Annual Congress, Denver, CO, May 5, 2017. Retrieved from

Table 1. Current CRF and Biomarker Studies and Trials in the Works

Project Title

Primary Investigator


Biomarker Type

Epigenetic Markers and Diurnal Levels of Fatigue During Chemotherapy

B. Aouizerat

New York University

DNA methylation

Epigenetic Mechanisms of Inflammation and Fatigue in Head and Neck Cancer Patients

C. Xiao


Epigenetic changes

Multimodal MRI Biomarker of Mild Cognitive Impairment in Breast Cancer

J. Wefel, S. Kesler

University of Texas MD Anderson Cancer Center


Inflammation-Induced CNS Glutamate During Breast Cancer Treatment

A. Miller



Biobehavioral Effects of Qigong for Prostate Cancer Survivors With Fatigue

A. Kinney

University of New Mexico Health Sciences Center

Gene expression

Biomarkers of Molecular Age to Predict the Toxicity of Cancer Chemotherapy

N. Sharpless, A. Elam, N. Mitin, H. Muss

University of North Carolina at Chapel Hill


Exploring Biological Linkage Between Circadian Disruption and Cancer Progression

B.J. Hahm

Seoul National University Hospital

Epigenetic changes, gene polymorphism

CRF, cancer-related fatigue; MRI, magnetic resonance imaging; CNS, central nervous system.