Cancer-related fatigue is a

symptom Signs and symptoms are the observed or detectable signs, and experienced symptoms of an illness, injury, or condition. A sign for example may be a higher or lower temperature than normal, raised or lowered blood pressure or an abnormality showin ...

fatigue Fatigue describes a state of tiredness that does not resolve with rest or sleep. In general usage, fatigue is synonymous with extreme tiredness or exhaustion that normally follows prolonged physical or mental activity. When it does not resolve ...

that is experienced by nearly all

cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...

patients. Among patients receiving cancer treatment other than surgery, it is essentially universal. Fatigue is a normal and expected side effect of most forms of

chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...

radiation therapy Radiation therapy or radiotherapy, often abbreviated RT, RTx, or XRT, is a therapy using ionizing radiation, generally provided as part of cancer treatment to control or kill malignant cells and normally delivered by a linear accelerator. Radia ...

, and

biotherapy A biopharmaceutical, also known as a biological medical product, or biologic, is any pharmaceutical drug product manufactured in, extracted from, or semisynthesized from biological sources. Different from totally synthesized pharmaceuticals, th ...

. On average, cancer-related fatigue is "more severe, more distressing, and less likely to be relieved by rest" than fatigue experienced by healthy people. It can range from mild to severe, and may be either temporary or a long-term effect. Fatigue may be a symptom of the cancer, or it may be the result of treatments for the cancer.

Pathophysiology

The

pathophysiology Pathophysiology ( physiopathology) – a convergence of pathology with physiology – is the study of the disordered physiological processes that cause, result from, or are otherwise associated with a disease or injury. Pathology is the ...

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 treatment Cancer can be treated by surgery, chemotherapy, radiation therapy, hormonal therapy, targeted therapy (including immunotherapy such as monoclonal antibody therapy) and synthetic lethality, most commonly as a series of separate treatments (e.g. ...

s. Fatigue is a common

of cancer. Some fatigue is caused by cancer treatments. This may show a characteristic pattern. For example, people on many

chemotherapy regimen A chemotherapy regimen is a regimen for chemotherapy, defining the drugs to be used, their dosage, the frequency and duration of treatments, and other considerations. In modern oncology, many regimens combine several chemotherapy drugs in combinat ...

s often feel more fatigue in the week after treatments, and less fatigue as they recover from that round of medications. People receiving

, by contrast, often find their fatigue steadily increases until the end of treatment. Proposed mechanisms by which cancer can cause fatigue include an increase in

pro-inflammatory cytokine An inflammatory cytokine or proinflammatory cytokine is a type of signaling molecule (a cytokine) that is secreted from immune cells like helper T cells (Th) and macrophages, and certain other cell types that promote inflammation. They include in ...

s, dysregulation of the hypothalamic-pituitary-adrenal axis, disruption of

circadian rhythm A circadian rhythm (), or circadian cycle, is a natural, internal process that regulates the sleep–wake cycle and repeats roughly every 24 hours. It can refer to any process that originates within an organism (i.e., Endogeny (biology), endogeno ...

s, muscle loss and cancer wasting, and genetic problems. Additionally, some forms of cancer may cause fatigue through more direct mechanisms, such as a

leukemia Leukemia ( also spelled leukaemia and pronounced ) is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or ' ...

that causes

anemia Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, th ...

by preventing the

bone marrow Bone marrow is a semi-solid tissue found within the spongy (also known as cancellous) portions of bones. In birds and mammals, bone marrow is the primary site of new blood cell production (or haematopoiesis). It is composed of hematopoietic ce ...

from producing blood cells efficiently. A relationship between

Interleukin 6 Interleukin 6 (IL-6) is an interleukin that acts as both a pro-inflammatory cytokine and an anti-inflammatory myokine. In humans, it is encoded by the ''IL6'' gene. In addition, osteoblasts secrete IL-6 to stimulate osteoclast formation. Smooth ...

and fatigue has been observed in studies, albeit inconsistently. Increased markers of

sympathetic nervous system The sympathetic nervous system (SNS) is one of the three divisions of the autonomic nervous system, the others being the parasympathetic nervous system and the enteric nervous system. The enteric nervous system is sometimes considered part of th ...

activity are also associated with cancer related fatigue.

Screening

The

National Comprehensive Cancer Network National Comprehensive Cancer Network (NCCN) is an alliance of 32 cancer centers in the United States, most of which are designated by the National Cancer Institute (one of the U.S. National Institutes of Health) as comprehensive cancer centers. It ...

recommends that every cancer patient be systematically screened for fatigue at the first visit with an

oncologist Oncology is a branch of medicine that deals with the study, treatment, diagnosis and prevention of cancer. A medical professional who practices oncology is an ''oncologist''. The name's etymological origin is the Greek word ὄγκος (''ó ...

, throughout treatment, and afterwards.

Screening Screening may refer to: * Screening cultures, a type a medical test that is done to find an infection * Screening (economics), a strategy of combating adverse selection (includes sorting resumes to select employees) * Screening (environmental), a ...

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.

Diagnosis

Some causes of cancer-related fatigue are treatable, and evaluation is directed towards identifying these treatable causes. Treatable causes of cancer-related fatigue include:

pain Pain is a distressing feeling often caused by intense or damaging stimuli. The International Association for the Study of Pain defines pain as "an unpleasant sensory and emotional experience associated with, or resembling that associated with, ...

emotional distress In medicine, distress is an aversive state in which a person is unable to completely adapt to stressors and their resulting stress and shows maladaptive behaviors. It can be evident in the presence of various phenomena, such as inappropriate so ...

sleep disturbance A sleep disorder, or somnipathy, is a medical disorder of an individual's sleep patterns. Some sleep disorders are severe enough to interfere with normal physical, mental, social and emotional functioning. Polysomnography and actigraphy are test ...

s, nutritional disturbances, decreased

physical fitness Physical fitness is a state of health and well-being and, more specifically, the ability to perform aspects of Outline of sports, sports, occupations and daily activities. Physical fitness is generally achieved through proper nutrition, moderate ...

and activity, side effects from medications (e.g.,

sedative A sedative or tranquilliser is a substance that induces sedation by reducing irritability or excitement. They are CNS depressants and interact with brain activity causing its deceleration. Various kinds of sedatives can be distinguished, but t ...

s),

abuse of alcohol Alcohol abuse encompasses a spectrum of unhealthy alcohol drinking behaviors, ranging from binge drinking to alcohol dependence, in extreme cases resulting in health problems for individuals and large scale social problems such as alcohol-r ...

or other substances. Additionally, other medical conditions, such as

infection An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable dise ...

heart disease Cardiovascular disease (CVD) is a class of diseases that involve the heart or blood vessels. CVD includes coronary artery diseases (CAD) such as angina and myocardial infarction (commonly known as a heart attack). Other CVDs include stroke, hea ...

, or endocrine dysfunction (e.g.,

hot flashes Hot flashes (also known as hot flushes) are a form of flushing, often caused by the changing hormone levels that are characteristic of menopause. They are typically experienced as a feeling of intense heat with sweating and rapid heartbeat, and ...

), can cause fatigue, and may also need treatment.

Definition

The

defines cancer-related fatigue as "a distressing persistent, subjective sense of physical, emotional and/or cognitive tiredness or exhaustion related to cancer or cancer treatment that is not proportional to recent activity and interferes with usual functioning". Cancer-related fatigue is a chronic fatigue (persistent fatigue not relieved by rest), but it is not related to

chronic fatigue syndrome Chronic fatigue syndrome (CFS), also called myalgic encephalomyelitis (ME) or ME/CFS, is a complex, debilitating, long-term medical condition. The causes and mechanisms of the disease are not fully understood. Distinguishing core symptoms are ...

Management

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 Occupational therapists (OTs) are health care professionals specializing in occupational therapy and occupational science. OTs and occupational therapy assistants (OTAs) use scientific bases and a holistic perspective to promote a person's abilit ...

. 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 Physical therapy (PT), also known as physiotherapy, is one of the allied health professions. It is provided by physical therapists who promote, maintain, or restore health through physical examination, diagnosis, management, prognosis, patient ...

. Engaging in moderate activity reduces fatigue. While

antidepressant Antidepressants are a class of medication used to treat major depressive disorder, anxiety disorders, chronic pain conditions, and to help manage addictions. Common side-effects of antidepressants include dry mouth, weight gain, dizziness, hea ...

s are ineffective at reducing fatigue in non-depressed cancer patients, psychostimulants such as

methylphenidate Methylphenidate, sold under the brand names Ritalin and Concerta among others, is the most widely prescribed central nervous system (CNS) stimulant medication used to treat attention deficit hyperactivity disorder (ADHD) and, to a lesser extent, ...

and

amphetamine Amphetamine (contracted from alpha- methylphenethylamine) is a strong central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, and obesity. It is also commonly used ...

s may reduce fatigue in some patients. 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. Pain,

difficulty breathing Shortness of breath (SOB), also medically known as dyspnea (in AmE) or dyspnoea (in BrE), is an uncomfortable feeling of not being able to breathe well enough. The American Thoracic Society defines it as "a subjective experience of breathing disc ...

, 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.

Addressing specific causes

If the fatigue is caused or exacerbated by a specific medical condition, such as anemia, then treatment of that medical condition should reduce the fatigue. *

Anemia Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, th ...

: Loss of oxygen-carrying red blood cells is a common cause of fatigue. Medications to improve blood production or

blood transfusion Blood transfusion is the process of transferring blood products into a person's circulation intravenously. Transfusions are used for various medical conditions to replace lost components of the blood. Early transfusions used whole blood, but mo ...

s frequently reduce fatigue. *

Pain Pain is a distressing feeling often caused by intense or damaging stimuli. The International Association for the Study of Pain defines pain as "an unpleasant sensory and emotional experience associated with, or resembling that associated with, ...

: A variety of approaches to managing

cancer pain Pain in cancer may arise from a tumor compressing or infiltrating nearby body parts; from treatments and diagnostic procedures; or from skin, nerve and other changes caused by a hormone imbalance or immune response. Most chronic (long-lasting) pa ...

may be used, particularly

analgesic An analgesic drug, also called simply an analgesic (American English), analgaesic (British English), pain reliever, or painkiller, is any member of the group of drugs used to achieve relief from pain (that is, analgesia or pain management). It ...

medications. *

Emotional distress In medicine, distress is an aversive state in which a person is unable to completely adapt to stressors and their resulting stress and shows maladaptive behaviors. It can be evident in the presence of various phenomena, such as inappropriate so ...

: Anxiety and depression are strongly associated with fatigue in cancer patients.

Psychosocial The psychosocial approach looks at individuals in the context of the combined influence that psychological factors and the surrounding social environment have on their physical and mental wellness and their ability to function. This approach is ...

treatments directed at reducing stress and increasing

coping skill Coping refers to conscious strategies used to reduce unpleasant emotions. Coping strategies can be cognitions or behaviours and can be individual or social. Theories of coping Hundreds of coping strategies have been proposed in an attempt to ...

s may reduce fatigue. Additionally, some patients in active treatment worry that the fatigue indicates treatment failure, and this anxiety may increase their fatigue in a

vicious cycle A vicious circle (or cycle) is a complex chain of events that reinforces itself through a feedback loop, with detrimental results. It is a system with no tendency toward equilibrium (social, economic, ecological, etc.), at least in the short r ...

. Education about fatigue as a normal side effect can reassure the patient. Up to 25% of cancer patients will experience depression. *

Sleep disturbance A sleep disorder, or somnipathy, is a medical disorder of an individual's sleep patterns. Some sleep disorders are severe enough to interfere with normal physical, mental, social and emotional functioning. Polysomnography and actigraphy are test ...

s: Patients who do not sleep well are more tired than others. Cancer patients commonly experience

insomnia Insomnia, also known as sleeplessness, is a sleep disorder in which people have trouble sleeping. They may have difficulty falling asleep, or staying asleep as long as desired. Insomnia is typically followed by daytime sleepiness, low energy, ...

hypersomnia Hypersomnia is a neurological disorder of excessive time spent sleeping or excessive sleepiness. It can have many possible causes (such as seasonal affective disorder) and can cause distress and problems with functioning. In the fifth edition ...

. Sleep disturbances may be caused by sleeping too much during the day, by

restless leg syndrome Restless legs syndrome (RLS), also known as Willis-Ekbom disease (WED), is generally a long-term disorder that causes a strong urge to move one's legs. There is often an unpleasant feeling in the legs that improves somewhat by moving them. This ...

, by pain, by anxiety, or by other medical conditions, like

obstructive sleep apnea Obstructive sleep apnea (OSA) is the most common sleep-related breathing disorder and is characterized by recurrent episodes of complete or partial obstruction of the upper airway leading to reduced or absent breathing during sleep. These episod ...

menopause Menopause, also known as the climacteric, is the time in women's lives when menstrual periods stop permanently, and they are no longer able to bear children. Menopause usually occurs between the age of 47 and 54. Medical professionals often d ...

. Practicing good

sleep hygiene Sleep hygiene is a behavioral and environmental practice developed in the late 1970s as a method to help people with mild to moderate insomnia. Clinicians assess the sleep hygiene of people with insomnia and other conditions, such as depression, ...

may reduce fatigue by improving sleep quality. * Nutritional disturbances: Patients may have difficulty eating, may not be absorbing food well, or may have chosen an extreme diet as an

alternative cancer treatment Alternative cancer treatment describes any cancer treatment or practice that is not part of the conventional standard of cancer care. These include special diets and exercises, chemicals, herbs, devices, and manual procedures. Most alternative ...

Loss of appetite Anorexia is a medical term for a loss of appetite. While the term in non-scientific publications is often used interchangeably with anorexia nervosa, many possible causes exist for a loss of appetite, some of which may be harmless, while others i ...

diarrhea Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin wi ...

and

vomiting Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the Human nose, nose. Vomiting can be the result of ailments like Food-poisoning, foo ...

may result in the patient consuming too few calories or becoming dehydrated. * Lack of

physical activity Physical activity is defined as any voluntary bodily movement produced by skeletal muscles that requires energy expenditure.Global Recommendations on Physical Activity for Health, 2009. World Health Organization. Geneva, Switzerland. Accessed 13/ ...

: Decreased physical activity can make fatigue worse by reducing endurance and muscle strength. Participating in regular aerobic and muscle-strengthening physical activity both during and after cancer treatment may reduce cancer-related fatigue. Current physical activity guidelines recommend adults with cancer to engage in at least 150 minutes per week of moderate- intensity or 75 minutes per week of vigorous-intensity aerobic physical activity, or an equivalent combination. It is also recommended to perform muscle-strengthening physical activity two to three times a week, although there are studies showing that aerobic training is better at mitigating symptoms of cancer-related fatigue and reduces the risk of post exercise malaise. Physical activities should be tailored to individual needs and physical abilities. * Side effects from medications: Fatigue and sleepiness are known side effects with some kinds of medications. Sometimes a change of medication, the dose, or the timing of the medication may result in less fatigue. For example, an

antihistamine Antihistamines are drugs which treat allergic rhinitis, common cold, influenza, and other allergies. Typically, people take antihistamines as an inexpensive, generic (not patented) drug that can be bought without a prescription and provides re ...

might be taken shortly before sleep, rather than in the middle of the day. *

Substance abuse Substance abuse, also known as drug abuse, is the use of a drug in amounts or by methods which are harmful to the individual or others. It is a form of substance-related disorder. Differing definitions of drug abuse are used in public health, ...

Alcohol Alcohol most commonly refers to: * Alcohol (chemistry), an organic compound in which a hydroxyl group is bound to a carbon atom * Alcohol (drug), an intoxicant found in alcoholic drinks Alcohol may also refer to: Chemicals * Ethanol, one of sev ...

marijuana Cannabis, also known as marijuana among other names, is a psychoactive drug from the cannabis plant. Native to Central or South Asia, the cannabis plant has been used as a drug for both recreational and entheogenic purposes and in various tra ...

, and many other drugs can produce fatigue as a side effect. * Other medical conditions: Cancer and its treatment usually put intense physical stress on the body, which can exacerbate other medical conditions. Additionally, fatigue may result from an infection.

Prognosis

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 survivor A cancer survivor is a person with cancer of any type who is still living. Whether a person becomes a survivor at the time of diagnosis or after completing treatment, whether people who are actively dying are considered survivors, and whether ...

s report fatigue. Under looser definitions, up to half of cancer survivors report fatigue. However, these studies are largely limited to patients with

breast cancer Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or a re ...

, or peripheral

stem cell transplant Hematopoietic stem-cell transplantation (HSCT) is the transplantation of multipotent hematopoietic stem cells, usually derived from bone marrow, peripheral blood, or umbilical cord blood in order to replicate inside of a patient and to produc ...

bone marrow transplant Hematopoietic stem-cell transplantation (HSCT) is the transplantation of multipotent hematopoietic stem cells, usually derived from bone marrow, peripheral blood, or umbilical cord blood in order to replicate inside of a patient and to produce ...

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. Receiving multiple types of treatments, such as chemotherapy and radiation, is associated with more fatigue. Older adults have a higher risk of long-term fatigue.

Cancer-related fatigue after treatment for childhood cancer.

Cancer-related fatigue has consistently been found to be one of the most prevalent and distressing symptoms in childhood cancer survivors. The International Late Effects of Childhood Cancer Guidelines Harmonization Group (IGHG) has published recommendations regarding the surveillance of fatigue in survivors of childhood cancer. 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. 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.

References

{{reflist, 30em Paraneoplastic syndromes