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Fatigue Time Warp

Kagan, Sarah H. PhD, RN

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doi: 10.1097/NCC.0000000000000654
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Cancer-related fatigue (CRF) exists in a time warp. Looking back, I recall the promise of work by Barbara Piper et al1 and others pioneering CRF science. Now, 3 decades on, I wonder why our clinical practice remains static. I need look no farther than the state of the science. Leak Bryant and colleagues,2 summarizing 40 years of progress in CRF, present a hopeful argument. Some progress is indeed evident. Mechanisms are better understood.3 Evidence for intervention is building.4 The science of mechanisms and that of intervention, however, are strikingly mismatched.

Dissonance between the science of CRF mechanisms and of interventions leaves practice trapped in a 20th-century time warp. Mechanisms appear largely cellular, including inflammation and neuroendocrine factors.3,5 Notably, science exposing specific mechanisms within particular cancers, as well as different cancer treatments, is spare. Ramifications of epigenetic biomarkers and phenomena such as sarcopenia and frailty, along with comorbid conditions, remain obscure. Conversely, CRF interventions are overwhelmingly behavioral. Origins of fatigue rest in cells and intercellular communication, yet we persist in pursuing general behavioral treatment. Such interventions likely offer some physiological effect along with corollary psychological feedback if fatigue lessens. Critically, these interventions lack precision in the era of personalized medicine.

Comparing CRF with advances in cancer treatment highlights how little real progress exists. Where targeted cancer therapies abound, most CRF treatment is imprecise and unsurprisingly ineffective.4 Nurses prepare people starting treatment for heartening outcomes and simultaneously teach them to expect fatigue. We recommend imprecise but healthful guidance for aerobic exercise, healthy diet and hydration, and, occasionally, mind-body practices. We rarely recommend pharmacotherapy with caffeine or methylphenidate, acknowledging limited effectiveness, and side effects preclude most people, especially those who are frail and multimorbid, from using them.

The culture of cancer care and broader social construction of cancer entail “fighting” cancer, implying risks of wounds. Cancer treatment toxicity, with CRF as the most common toxicity, is often a first wound. With wounding in mind, we tolerate such a risk for the young and fret about it for the old, expressing persistent ageism in cancer care.6 Given this cultural context, cancer treatment toxicity seems expected to such a degree that CRF research and practice lag.

Drawing a parallel of “most common” illustrates how such cultural expectations limit our science. Cancer-related fatigue is widely acknowledged as the most common cancer treatment toxicity and is likely a significant part of living with cancer and other chronic conditions. Multimorbid individuals are typically older and incur a greater risk of CRF than younger people, although this equation of age and comorbidity varies.7 Our science offers little to differentiate epigenetics of age, multimorbidity, specific malignancies, and treatment responses. Consequently, CRF management for most patients and survivors, who are on average older and multimorbid, is incomplete. Would we accept this state of treatment effectiveness and outcomes if breast cancer, the most common cancer globally, were the focus?

This fatigue time warp exhausts me (pun intended). In this time of epigenetics, therapeutic targets, and personalized medicine, I encourage us as nurses to transform CRF science and practice. Let us work to align and advance science, addressing profound needs among those living with CRF. Imagine specific epigenetic targets such as neurotransmitters and other biomarkers matched to precise behavioral and pharmacological treatments. People living with CRF await our leadership.


1. Piper BF, Lindsey AM, Dodd MJ. Fatigue mechanisms in cancer patients: developing nursing theory. Oncol Nurs Forum. 1987;14(6):17–23.
2. Leak Bryant A, Walton AL, Phillips B. Cancer-related fatigue: scientific progress has been made in 40 years. Clin J Oncol Nurs. 2015;19(2):137–139.
3. Bower JE. Cancer-related fatigue—mechanisms, risk factors, and treatments. Nat Rev Clin Oncol. 2014;11:597.
4. Mustian KM, Alfano CM, Heckler C, et al. Comparison of pharmaceutical, psychological, and exercise treatments for cancer-related fatigue: a meta-analysis. JAMA Oncol. 2017;3(7):961–968.
5. Saligan LN, Olson K, Filler K, et al. The biology of cancer-related fatigue: a review of the literature. Support Care Cancer. 2015;23(8):2461–2478.
6. Lawler M, Selby P, Aapro MS, Duffy S. Ageism in cancer care. BMJ. 2014;348:g1614.
7. Götze H, Köhler N, Taubenheim S, Lordick F, Mehnert A. Polypharmacy, limited activity, fatigue and insomnia are the most frequent symptoms and impairments in older hematological cancer survivors (70+): findings from a register-based study on physical and mental health. J Geriatr Oncol. 2018. Accessed September 20, 2018.
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