Cancer-related fatigue

The pathophysiology of cancer-related fatigue is poorly understood. It may be caused by the cancer or the effects it has on the body, by the body's response to the cancer, or by the cancer treatments.

Fatigue is a common symptom of cancer.[2]

Some fatigue is caused by cancer treatments. This may show a characteristic pattern. For example, people on many chemotherapy regimens often feel more fatigue in the week after treatments, and less fatigue as they recover from that round of medications. People receiving radiation therapy, by contrast, often find their fatigue steadily increases until the end of treatment.[2]

Proposed mechanisms by which cancer can cause fatigue include an increase in pro-inflammatory cytokines, dysregulation of the hypothalamic-pituitary-adrenal axis, disruption of circadian rhythms, muscle loss and cancer wasting, and genetic problems.[1] Additionally, some forms of cancer may cause fatigue through more direct mechanisms, such as a leukemia that causes anemia by preventing the bone marrow from producing blood cells efficiently. A relationship between Interleukin 6 and fatigue has been observed in studies, albeit inconsistently. Increased markers of sympathetic nervous system activity are also associated with cancer related fatigue.[3]

The National Comprehensive Cancer Network recommends that every cancer patient be systematically screened for fatigue at the first visit with an oncologist, throughout treatment, and afterwards.[1] Screening typically involves a simple question, like "On a scale of one to ten, how tired have you felt during the last week?"

More detailed information may be collected in a symptom journal.

Some causes of cancer-related fatigue are treatable, and evaluation is directed towards identifying these treatable causes. Treatable causes of cancer-related fatigue include: anemia, pain, emotional distress, sleep disturbances, nutritional disturbances, decreased physical fitness and activity, side effects from medications (e.g., sedatives), abuse of alcohol or other substances.[1] Additionally, other medical conditions, such as infections, heart disease, or endocrine dysfunction (e.g., hot flashes), can cause fatigue, and may also need treatment.

Treatment depends on the patient's overall situation. A patient who is in active treatment may have different priorities than a person who has completed treatment, or who is at the end of life.

Some management strategies may help all patients and could be supported by the work of an Occupational Therapist. These include scheduling high-priority tasks during the patient's best time of day, using labor-saving devices, delegating tasks to caregivers, and avoiding unimportant activities, so that the patient will have more energy available for other activities.

Patients who are not at the end of life may benefit from physical exercise or physical therapy. Engaging in physical activity may reduce fatigue.[1][4][5][6]

While antidepressants are ineffective at reducing fatigue in non-depressed cancer patients, psychostimulants such as methylphenidate and amphetamines may reduce fatigue in some patients.[1][7][8][9][10]

At the end of life, fatigue is usually associated with other symptoms, especially anemia, side effects from many medications and previous treatments, and poor nutritional status.[1] Pain, difficulty breathing, and fatigue form a common symptom cluster. Fatigue often increases as patients with advanced cancer approach death. As a result, people who are dying often sleep much more than a healthy person.

Fatigue caused by the cancer or its treatment often resolves if treatment is successful. However, some patients experience long-term or chronic fatigue. When strict definitions are used, about 20% of long-term, disease-free cancer survivors report fatigue.[1] Under looser definitions, up to half of cancer survivors report fatigue.[1] However, these studies are largely limited to patients with breast cancer, or peripheral stem cell transplant or bone marrow transplant patients, and the incidence may be different for survivors of other cancers.

Experiencing fatigue before treatment, being depressed or anxious, getting too little exercise, and having other medical conditions are all associated with higher levels of fatigue in post-treatment cancer survivors.[1] Receiving multiple types of treatments, such as chemotherapy and radiation, is associated with more fatigue.[2] Older adults have a higher risk of long-term fatigue.[2]

Cancer-related fatigue has consistently been found to be one of the most prevalent and distressing symptoms in childhood cancer survivors.[14] The International Late Effects of Childhood Cancer Guidelines Harmonization Group (IGHG) has published recommendations regarding the surveillance of fatigue in survivors of childhood cancer. [15] These recommendations include regular screenings of fatigue in survivors of childhood cancer. Survivors of pediatric brain tumors report more fatigue after end of treatment than survivors of acute lymphoblastic leukemia, but both groups experience more fatigue than healthy children and adolescents.[16] While considered a long-term effect of the treatment, children and adolescents experience fatigue already during the treatment for acute lymphoblastic leukemia and this side-effect of treatment remains in some patients after the treatment has ended.[17] Fatigue after treatment for pediatric brain tumors does not automatically resolve itself, but requires surveillance and interventions.[18]