Difficult-to-treat, cancer-related fatigue is a common, distressing clinical issue. It impedes daily activities, severely affecting patients’ quality of life. Compounding the problem is a lack of consensus on an effective pharmacologic intervention. Acupressure is a traditional Chinese medicine technique that involves stimulation of specific acupoints on the body or in the ear to relieve chronic pain symptoms, including those associated with cancer. In this article, Ms. Zick and Dr. Harris summarize the research on acupressure for managing cancer-related fatigue. 

Suzanna M. Zick, ND, MPH

Richard E. Harris, PhD

Overview 

MODERATE TO severe persistent cancer-related fatigue occurs in about 25% to 80% of people living with cancer^1-3 and can last for as long as 10 years after the end of treatment. Yet it is often not assessed, has limited treatment options, and is associated with significant barriers to implementing current treatments.^4-7 In contrast to the fatigue experienced by healthy people at the end of a long day, persistent cancer-related fatigue is defined by the National Comprehensive Cancer Network® (NCCN®) and used by the ASCO Clinical Practice Guidelines as “a distressing, persistent, subjective sense of physical, emotional, and/or cognitive tiredness or exhaustion related to cancer and/or cancer treatment that is not proportional to recent activity and significantly interferes with usual functioning.”⁴ Congruent with this definition, persistent cancer-related fatigue is associated with significant health issues, including higher rates of depression and anxiety,⁸ poor sleep,⁹ and decreased quality of life.¹⁰ Furthermore, sufferers of persistent cancer-related fatigue are often unable to perform their daily activities of living and/ or assist their family in these activities, leading to further physical and psychosocial problems.¹¹ 

Causes of Cancer-Related Fatigue 

THE CAUSES of persistent cancer-related fatigue are poorly understood, likely given the multiple interrelated factors in any given individual and because they are a combination of immune, muscular, endocrine, and neurochemical changes.¹² The mechanisms underlying persistent cancer-related fatigue with the most evidence include elevated levels of proinflammatory cytokines (interleukin-6, tumor necrosis factor–alpha) and C-reactive protein in fatigued vs nonfatigued patients with cancer^13-15; suppressed hypothalamic-pituitary-adrenal axis and consequent blunting of the stress response leading to both increased circulating cortisol and inflammation; and circadian rhythm disruption with fatigued patients with cancer and survivors having a flatter diurnal slope and a slower decline of evening cortisol.^16,17 

Another emerging potential mechanism is dysfunctional activity in the brain, with fatigued breast cancer survivors having alterations in brain neurochemistry such as elevated excitatory neurotransmitters (ie, glutamate) within the posterior insula and disturbed functional connectivity to the default mode network, compared with the nonfatigued population.^18,19 These changes in brain function and chemistry appear to be related to patients’ symptoms of poor sleep and fatigue.¹⁸ 

Acupressure for Cancer-Related Fatigue 

ACUPRESSURE IS a component of traditional Chinese medicine where a finger, thumb, or a device is used to stimulate—usually in a clockwise or counterclockwise circular motion—acupoints on the body, or in the ear in the case of auricular acupressure. Acupoints are located throughout the body along meridians, and stimulation of these points is used to alleviate illness and improve symptoms such as fatigue. Acupressure can either be provided as a treatment by a traditional Chinese medicine practitioner; an acupuncturist; or a patient, who can be taught to self-administer the treatment. The number and location of acupoints being stimulated depend on the symptom or illness being treated. For example, in clinical trials to treat cancer-related fatigue, 5 to 7 acupoints were stimulated for up to 3 minutes each.^20-29 Auricular acupressure involves placing small seeds on acupoints in the ear. These seeds are tapped in place, and patients are asked to rub or stimulate them throughout the day. 

A total of 11 randomized controlled trials of acupressure for fatigue in 949 patients with cancer have been conducted to date.^20-31 The majority of these studies have been conducted in the breast cancer population (n = 6,537 women),^22-25,27,30 but trials have also been conducted in those with hepatocellular carcinoma (n = 1),²¹ lung cancer (n = 2),^28,29 ovarian cancer (n = 1),³¹ and pediatric acute lymphocytic leukemia (n = 1).²⁰ These studies are extremely heterogeneous differing not only in the patient population, but also in the control group (eg, sham acupressure, usual care, acupuncture), the duration and frequency of acupressure treatments, how and when fatigue is assessed, when acupressure to the cancer arch is administered, and in the acupressure intervention itself. For the latter, acupressure has been administered by a traditional Chinese medicine provider; self-administered; delivered as auricular acupressure; or combined with other therapies such as aerobic exercise, essential oils, and education. Also, with the exception of trials in breast cancer survivors (n = 288)²⁵ and in acute lymphoblastic leukemia (n = 120),²⁰ studies have been small feasibility assessments. 

Jun J. Mao, MD, MSCE

Acupressure has been shown to be safe and acceptable to patients with cancer.^20-31 Also, acupressure appears to affect significant improvements, on the order of 30% to 40%, in fatigue severity and interference compared with usual care, although fewer effects are typically seen with sham acupressure controls.^20-31 However, given the high heterogeneity and the poor quality of some of the studies, the data need to be viewed with caution. 

Mechanistic studies indicate that acupressure may impact brain chemistry and connectivity, which was found to be different in the brains of fatigued cancer survivors than in nonfatigued cancer survivors, A relatively recent brain neuroimaging study found that 6 weeks of 2 distinct formulas (acupoints located in distinct areas of the body from one another) of once-daily self-acupressure in fatigued breast cancer survivors increased connectivity between the default mode network and different thalamus/brain stem areas related to sleep (for a relaxing acupressure formula) and alertness (for a stimulating acupressure formula). The authors suggested that different acupressure points may have specificity in relation to symptoms treated in fatigued patients with cancer.³² 

Closing Thoughts 

FATIGUE CAN cause significant physical and emotional burdens on patients with cancer. Acupressure appears useful from a clinician’s perspective, as it is safe, affordable, and often does not require repeated patient-provider visits. As such, acupressure may have utility for cancer survivors with fatigue. ■

DISCLOSURE: Drs. Zick and Harris helped create an acupressure app called MeTime Acupressure. Dr. Harris is also a consultant or advisor to Pfizer Inc. and Aptinyx. 

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