Fatigue is a common symptom of advanced mesothelioma. Fatigue is also commonly linked with cancer treatment and has an occurrence rate of 90% among patients receiving chemotherapy. There are many potentially underlying causes for both the symptoms. In majority of patients, the etiology of both the symptoms is multifactorial, with several of these contributing interrelated abnormalities. For instance, in a study involving patients with advanced cancer, it was noticed that fatigue correlated significantly with the intensity of dyspnea. This article will elaborate on the mechanisms, clinical features, assessment, and management of fatigue and dyspnea, which are two of the most common and often undertreated symptoms among cancer patients.
The National Comprehensive Cancer Network defines cancer-related fatigue as “a distressing, persistent, subjective sense of tiredness or exhaustion related to cancer or cancer treatment that is not proportional to recent activity and interferes with usual functioning.” Fatigue is often severe among cancer patients; has an identifiable anticipatory component; and results in general malaise, lack of energy, diminished mental functioning, and lethargy, all of which significantly impair quality of life. Fatigue can occur early during the progression of the disease; may worsen due to treatment, and can be found in almost all individuals with advanced cancer.
Sometimes, fatigue is referred to as tiredness, exhaustion, weakness, lack of energy, and asthenia. However, these terms may have varying implications for different patient populations. Further, different studies on fatigue and dyspnea have focused on different outcomes, which range from physical performance to just the subjective sensation.
The mechanisms involved in cancer-related fatigue are not clearly understood. It has been postulated that substances produced by the tumor result in fatigue. When blood from a fatigued subject was injected into a rested subject, it demonstrated manifestations of fatigue. When cytokines are produced in the host in response to the tumor, the same can also create a direct fatigue-inducing effect. Other potential causes of chemotherapy- or radiotherapy-induced fatigue include muscular or neuromuscular junction abnormalities. Hence, it can be concluded that fatigue results from not just one, but several different syndromes. In most patients with advanced cancer, multiple mechanisms are responsible for causing fatigue.
In an individual patient, there are often multiple causes of fatigue with many interrelated factors.
A complex interaction of host and tumor products leads to cancer cachexia. Host cytokines, for instance tumor necrosis factor, interleukin-1 (IL-1), and IL-6 can potentially cause reduced food consumption, loss of body weight, a reduction in synthesis of both proteins and lipids, and increased lipolysis. Profound weakness and fatigue can be caused by the metabolic abnormalities responsible for the production of cachexia as well as the loss of muscle mass due to progressive cachexia. However, there are several abnormalities that can cause profound fatigue in patients who may not be experiencing significant weight loss.
Reduced physical activity has demonstrated to cause deconditioning and diminished endurance to both physical exercise and routine daily activities. In comparison, overexertion is often the cause of fatigue among non-cancer patients. At risk are younger cancer patients receiving aggressive antineoplastic treatments, for instance radiation therapy and chemotherapy, and those who are making efforts to maintain their professional and social activities.
In case of non-cancer patients who experience fatigue, the final diagnosis in around 75% of patients is psychological (for instance anxiety, depression, and other types of psychological disorders). The occurrence rate of major psychiatric disorders among cancer patients is relatively low. Nonetheless, symptoms of adjustment disorders and psychological distress with anxious or depressive moods are more common. Fatigue is often the most prevalent symptom among patients with a major depressive disorder or adjustment disorder.
Low red blood cell count, if induced due to chemotherapy or advanced cancer, has been linked with fatigue, and treatment of the same helps improve symptoms of fatigue and quality of life among these patients. However, treatment of anemia among terminally ill patients may not help improve fatigue satisfactorily due to the multifactorial characteristic of its etiology. Fatigue can also occur due to the relatively more intense characteristics of other contributory factors.
Autonomic insufficiency is a medical complication that occurs frequently among patients with advanced cancer. Instances of autonomic failure have also been seen among patients with a specific type of severe chronic fatigue syndrome. While the connection between fatigue and autonomic dysfunction has not yet been established among cancer patients, the same should be suspected among patients with signs of autonomic failure including severe postural hypotension.