Cancer-Related Fatigue in Hospice: A Nudge to Action?

To the Editor:

Hospice interdisciplinary teams attend to patients’ physical, emotional, social, and spiritual concerns. This holistic lens is essential to high-quality end-of-life care, as research suggests that over 80% of hospice patients experience at least one potentially problematic symptom in their final days of life.¹ While this high symptom prevalence suggests a need for better symptom management for all hospice patients, the need may be most pronounced for patients with cancer, who tend to experience greater symptom burden than other hospice patients.¹

Fatigue, defined as “a persistent sense of tiredness [or] diminished energy … not relieved by [sleep or] rest,” has been repeatedly identified as one of the most common symptoms experienced by individuals with cancer.² Although it is a well-documented side effect of numerous disease-directed treatments, fatigue can occur before, during, after, or even in the absence of such treatments.³ Phongtankuel et al.’s study of nearly 400 home hospice patients (40% of whom had a primary diagnosis of cancer, none of whom were receiving disease-directed treatment) is one of the few examining fatigue in a U.S. hospice-specific population. Results indicated that fatigue was the most commonly experienced symptom and the one most likely to be rated as severe.¹

Additional research is needed to determine if prevalence and severity rates noted in prior studies of cancer-related fatigue are similar to those observed in a broader range of hospice settings. In addition, the patient experience of fatigue is understudied, leaving important questions unanswered. For example, given its high prevalence, is fatigue experienced as a non-distressing part of the normal dying process? Or, as is true at other points in the disease trajectory,⁴ is fatigue associated with diminished wellbeing among patients with cancer at the end of life? The study described herein was conducted to fill these gaps in the literature, answering the following research questions: (1) What is the prevalence and severity of fatigue among hospice patients with cancer? and (2) What is the relationship between fatigue and overall wellbeing in this patient population?

Methods

Researchers conducted a post-hoc secondary analysis of data collected during a randomized clinical trial of an intervention for family caregivers of hospice patients with cancer.⁵ Data included family caregiver proxy responses to two items from the Edmonton Symptom Assessment System – Revised (ESAS-r):⁶ a 0–10 severity rating for fatigue (0 = no fatigue, 10 = worst possible fatigue) and a 0–10 rating for wellbeing (0 = best possible wellbeing, 10 = worst possible wellbeing). Researchers calculated descriptive statistics to determine fatigue prevalence and severity. To examine the relationship between fatigue and wellbeing, they performed a Kendall’s tau-b correlation test due to departure from normality in variables under investigation and presence of ties in the data. Correlations were also performed for relationships between fatigue and other ESAS-r symptoms (pain, nausea, depression, anxiety, drowsiness, lack of appetite, and shortness of breath) to provide contextual information to support interpretation of findings. Missing data were handled via case-wise deletion.

Results

The analytic sample included 159 patients (see Table 1 for demographics). The mean patient fatigue rating was 7.57 (standard deviation [SD] = 1.92), and the mean patient wellbeing rating was 5.55 (SD = 2.44). All caregiver proxy ratings for fatigue were greater than 0, reflecting 100% prevalence in this sample. Patient fatigue and poor wellbeing were positively, statistically significantly correlated (tau = .29, p < .001). Table 2 details the correlations between fatigue and other ESAS-r symptoms. All symptoms except anxiety were positively, statistically significantly correlated with fatigue (p<.05).

Table 1:

Sample Description

	Overall (N=159)
Age
Mean (SD)	71.9 (14.9)
Median [Min, Max]	73.5 [27.0, 99.0]
Missing	11 (6.9%)
Race
Black/African American	10 (6%)
White	148 (93%)
Other	1 (1%)
Sex
Male	86 (54%)
Female	73 (46%)
Ethnicity
Non-Hispanic	155 (97%)
Hispanic	4 (3%)
Marital Status
Single, never partnered	16 (10%)
Partnered	74 (47%)
Divorced or separated	24 (15%)
Widowed	41 (26%)
Other	4 (3%)
Education
Less than high school	23 (15%)
High school or equivalent	60 (38%)
Some college/trade school	39 (25%)
Undergraduate degree	23 (15%)
Graduate/professional degree	12 (8%)
Other	1 (1%)
Missing	1 (0.6%)
Patient Residence
Private residence	120 (76%)
Nursing home	26 (17%)
Other	11 (7%)
Missing	2 (1.3%)
Patient Fatigue a
Mean (SD)	7.57 (1.92)
Median [Min, Max]	8.00 [1.00, 10.0]
Patient Wellbeing
Mean (SD)	5.55 (2.44)
Median [Min, Max]	6.00 [0, 10.0]
Patient Pain
Mean (SD)	4.40 (2.80)
Median [Min, Max]	5.00 [0, 10.0]
Missing	2 (1.3%)
Patient Nausea
Mean (SD)	2.19 (3.18)
Median [Min, Max]	0 [0, 10.0]
Missing	1 (0.6%)
Patient Depression
Mean (SD)	5.03 (2.89)
Median [Min, Max]	5.00 [0, 10.0]
Missing	2 (1.3%)
Patient Anxiety
Mean (SD)	4.59 (3.10)
Median [Min, Max]	5.00 [0, 10.0]
Missing	2 (1.3%)
Patient Drowsiness
Mean (SD)	6.66 (2.63)
Median [Min, Max]	7.00 [0, 10.0]
Patient Lack of Appetite
Mean (SD)	5.98 (3.23)
Median [Min, Max]	7.00 [0, 10.0]
Missing	2 (1.3%)
Patient Shortness of Breath
Mean (SD)	3.94 (3.06)
Median [Min, Max]	4.00 [0, 10.0]
Missing	1 (0.6%)

Note. SD = standard deviation. Min = minimum. Max = maximum.

^aReferred to as “tiredness” and defined as “lack of energy” in the ESAS-r

Table 2:

Correlation of Fatigue with Other Symptoms

Symptom	Estimatea	p value
Wellbeing	0.29	< 0.001
Pain	0.24	< 0.001
Nausea	0.26	< 0.001
Depression	0.20	0.001
Anxiety	0.09	0.121
Drowsiness	0.51	< 0.001
Lack of Appetite	0.34	< 0.001
Shortness of Breath	0.13	0.039

^aKendall’s tau correlations used for all estimates

Comment

These findings highlight numerous opportunities to improve end-of-life cancer care. Although the etiology of cancer-related fatigue is not well understood and likely multifactorial, clinical guidelines emphasize the need to screen for and appropriately treat the symptom at all stages of illness.⁴ Many echo the National Comprehensive Cancer Network (NCCN)’s assertion that fatigue in patients with cancer is “underreported, underdiagnosed, and undertreated” across the disease trajectory.⁴ Simple screening questions could be easily incorporated into routine hospice visits; however, given that fatigue is often comorbid with other symptoms (e.g., pain, mood and sleep disturbances), adoption of a more comprehensive screening tool (e.g. ESAS-r,⁶) may be more helpful in unmasking problems contributing to fatigue. When clinically indicated, other instruments can be used to facilitate an efficient, yet more in-depth assessment of fatigue. For example, the Brief Fatigue Inventory can be used to collect information on symptom presence, severity, and interference with daily functioning in approximately five minutes.⁷

The clinical response to cancer-related fatigue should be aligned with hospice patients and families’ values, preferences, and goals of care. In addition to screening, appropriate workup for fatigue may include a physical examination and review of the medication list to identify drugs that may be causing or worsening fatigue. With regard to treatments, although some (e.g., high-level physical activity) may be inappropriate for patients with functional limitations, others have clear potential for use in hospice care. Non-pharmacologic response options include emotional validation and acknowledgement of fatigue and related distress; education regarding realistic expectations and corresponding energy conservation strategies; and psychosocial interventions focused on meaning, dignity, and adaptation to change.⁴ While such interventions may not result in an increase in energy, they may reduce the distress caused by fatigue, thereby increasing patients’ qualify of life. Evidence is mixed regarding the efficacy of pharmacologic interventions in reducing cancer-related fatigue in patients’ final days, and research is needed to better understand if and how medications can be helpful to those experiencing end-of-life fatigue.⁴ Methylphenidate, a psychostimulant, is among the medications that have been identified as potentially helpful in treating fatigue, with the NCCN noting the medication’s potential side effects (e.g., headache, nausea), and advising that it “may be considered with caution for selected terminal patients.”⁴ Corticosteroids prednisone and dexamethasone have also been identified as promising tools to provide short-term relief from fatigue. However, experts caution against their long-term use and advise that these medications be restricted to patients presenting with a narrow range of symptoms and disease realities, given limited research on the medications’ effects longitudinally and/or with diverse patient populations.⁴ While routine use of pharmacologic interventions for fatigue may be deemed medically inappropriate or may conflict with hospice patients and families’ preferences, strategic use of medications may enable dying patients’ meaningful participation in special events such as family visits or short trips to favorite locations.

Study Limitations

Several study limitations warrant attention. First, reliance on caregiver proxy reports may have resulted in inaccurate estimates of the presence and severity of fatigue, as research suggests that caregivers tend to overestimate patient symptom experiences.⁸ Second, only single ESAS-r⁶ items were available to measure patient fatigue and problems with wellbeing in this secondary analysis, restricting measurement precision and depth. Finally, only cross-sectional data were analyzed, precluding examination of changes longitudinally.

Conclusion

Fatigue is a widespread and often distressing symptom that may be undertreated among hospice patients with cancer, despite a wide range of available pharmacologic and non-pharmacologic treatment options. Increased attention to this potentially debilitating symptom appears likely to improve patients’ quality of life by reducing their distress and/or strengthening their ability to participate in meaningful activity. In addition, research is needed to better understand terminal fatigue and identify additional treatment options. These study findings add to the small but growing body of evidence on cancer-related fatigue at end of life and may serve as a gentle but necessary nudge to action for hospice providers and researchers alike.