Cancer related fatigue (CRF) is a common and expected adverse reaction to both cancer and cancer treatments. The National Comprehensive Cancer Network (NCCN) defines CRF as “a distressing, persistent, subjective sense of physical, emotional, and /or cognitive tiredness or exhaustion related to cancer or cancer related treatment that is not proportional to recent activity and interferes with usual functioning” (Jankowski et. al., 2024). Studies have determined that 30% to 60% of patients undergoing cancer treatment experience moderate to severe fatigue. While the severity of fatigue improves with time for most patients upon completion of cancer treatment, studies have found that one quarter to one third of cancer survivors experience persistent fatigue up to ten years after treatment (Bower et al., 2014).
CRF is one of the most under-reported and under treated side effects of cancer and cancer treatment (Bower et. al., 2014). This tends to be especially true in the survivorship phase. It is likely under-reported due to patients feeling as if it is just a side effect that they have to deal with or feeling that there are no effective interventions. CRF is a symptom that should not be overlooked. Survivors with CRF experience negative consequences physically, mentally, and socially. CRF is associated with reduced employment, increased financial stress, and increased utilization of healthcare. More concerning, CRF is linked with increased mortality (Thong et al., 2020).
While a gold standard for treatment of CRF has not been established, studies have found benefit from multiple CRF treatment interventions. However, before an intervention for CRF can be prescribed, a thorough assessment or screening of contributing factors must be performed.
Meta-analysis has determined that CRF is likely multifactorial for most individuals impacted by this symptom. Some contributing factors identified include medical comorbidities, medications, nutritional issues, physical deconditioning, mood disturbance, and physical symptoms (Bower et al., 2014). Evidence suggests that CRF is the result of the combination of physical and psychological elements.
NCCN recommends a comprehensive assessment to aid in identifying the contributing factors of each individual’s CRF. A focused history should be performed, including disease status and treatment history, as well as a medication review. Equally important, providers should assess current social support and economic status/access to resources. Finally, a detailed history of fatigue should be assessed (Jankowski et. al., 2024).
In addition to the above-mentioned elements of CRF assessment, an assessment of treatable contributing factors should be performed (Jankowski et. al., 2024). Contributing factors may include emotional distress, anemia, sleep disturbance, nutritional deficit, decreased functional status, comorbidities, multi-organ dysfunction, and infection.
Multiple studies have determined that there is stronger evidence supporting nonpharmacological interventions for CRF, compared with pharmacological treatments. Examples of nonpharmacological interventions include aerobic exercise, yoga, cognitive-behavioral therapy (CBT) and psycho-educational interventions (Stone et. al., 2023).
There have been several randomized controlled trials including cancer patients that have demonstrated that exercise interventions are effective in alleviating CRF, both during and after cancer treatment (Stone et al., 2023). These findings suggest that exercise can be beneficial at multiple points during the disease and treatment process. Different types of physical exercise interventions have been studied, including both aerobic and resistance training. Meta-analysis shows that most interventions use a supervised first visit, followed by home based regimens. The duration of most regimens in the studies varied from four to 14 weeks. The most common form of aerobic exercise studied was walking (Stone et al., 2023). Additionally, some studies have demonstrated the benefit of group-based exercise programs leading to increased adherence (Thong et al., 2020).
NCCN has listed physical activity as a category 1 (high-level evidence, uniform consensus) intervention for CRF for patients on active treatment, post treatment, and end of life. Physical activity should consist of cardiovascular endurance as well as resistance training. Additionally, referral to physical therapy, occupational therapy, and physical medicine should be considered. Of note, NCCN also recommends yoga as a category 1 physical exercise intervention for CRF (Jankowski et. al., 2024).
Psychosocial interventions are another method of nonpharmacological approach to managing CRF. These interventions consist of therapies that focus on behaviors that perpetuate persistent fatigue, including “dysfunctional cognitions concerning fatigue, poor coping, fear of recurrence, dysregulation of sleep and activity patterns, and low social support” (Bower et. al., 2014). Psychosocial interventions include cognitive-behavioral therapy (CBT), a type of psychotherapy that helps an individual recognize and change maladaptive thoughts and behaviors. CBT may be especially beneficial if provided after completion of active treatment (Thong et. al., 2020). Additional methods of psychosocial intervention include mindfulness-based stress reduction, psychoeducational therapies, supportive expressive therapies, such as support groups, counseling, and journal writing (Jankowski et. al., 2024).
Some additional methods for treating CRF include sleep hygiene, involving stimulus control and sleep restriction during the day, and bright white light therapy (BWT). BWT has been recently added as a category 2A recommendation for CRF therapy by NCCN. This treatment requires patients to expose themselves to bright white light for a period of time every morning. The goal is to limit disruption to an individual’s circadian rhythm (Thong et. al., 2020). Acupuncture and nutritional consults are included in the list of nonpharmacological strategies for managing CRF as well (Jankowski et. al., 2024).
Pharmacological interventions may be helpful, however, there is a paucity of evidence to support the effectiveness of medications and supplements. Stimulants are a class of medication often used to treat CRF. Methylphenidate is the stimulant most commonly prescribed for CRF; however, ginseng is popular as well. Despite the use of these substances, the evidence supporting the use of stimulants remains limited (Stone et al., 2023). Additionally, the use of supplements in treating CRF cannot be supported due to lack of controlled trials demonstrating efficacy (Bower et. al., 2014).
The approach to managing CRF is multipronged. First, it is important to perform a thorough assessment of potential causes of a patient’s fatigue. Once sources of fatigue have been identified, an individualized care plan for CRF may be developed. Evidence from studies suggests that regular exercise if the most effective method of addressing CRF, however, exercise in combination with other nonpharmacological interventions can be significantly beneficial. Furthermore, including patient education about CRF in the care plan as well as providing mind-body interventions can help reduce CRF both during and after cancer treatment.
References
1. Jankowski C, Berger A, Aranha O, Banerjee C, Breitbart W, Carpenter K, et al. NCCN Guidelines Version 2.2024 Cancer-Related Fatigue. NCCN. 2024;https://www.nccn.org/. Evidence-based guidelines that are updated regularly and relate to patients on and off treatment and in patients at the end-of-life.
2. Bower JE. Cancer-related fatigue--mechanisms, risk factors, and treatments. Nat Rev Clin Oncol. 2014 Oct;11(10):597-609. doi: 10.1038/nrclinonc.2014.127. Epub 2014 Aug 12. PMID: 25113839; PMCID: PMC4664449.
3. Thong MSY, van Noorden CJF, Steindorf K, Arndt V. Cancer-Related Fatigue: Causes and Current Treatment Options. Curr Treat Options Oncol. 2020 Feb 5;21(2):17. doi: 10.1007/s11864-020-0707-5. Erratum in: Curr Treat Options Oncol. 2022 Mar;23(3):450-451. doi: 10.1007/s11864-021-00916-2. PMID: 32025928; PMCID: PMC8660748.
4. Stone P, Candelmi DE, Kandola K, Montero L, Smetham D, Suleman S, Fernando A, Rojí R. Management of Fatigue in Patients with Advanced Cancer. Curr Treat Options Oncol. 2023 Feb;24(2):93-107. doi: 10.1007/s11864-022-01045-0. Epub 2023 Jan 19. PMID: 36656503; PMCID: PMC9883329.
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