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INTRODUCTION

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Fatigue is the most common symptom among cancer patients and a common symptom among cancer survivors. Cancer-related fatigue (CRF) is defined 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.1 In comparison to the fatigue experienced by healthy individuals, CRF is more severe, more distressing,2,3 and less likely to be relieved by rest.4 The International Classification of Diseases, 10th revision (ICD-10), describes the CRF diagnostic criteria as follows5,6,7:

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  1. Six or more of 11 possible fatigue symptoms, with 1 being "significant fatigue," have been present every day or nearly every day during the same 2-week period in the past month.

  2. The symptoms cause clinically significant distress or impairment in important aspects of functioning.

  3. The symptoms are the result of cancer or cancer treatment.

  4. The symptoms are not primarily due to a comorbid psychiatric disorder.

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Fatigue is a symptom with multiple dimensions that includes physical, emotional, and mental aspects. It can be experienced anywhere along the spectrum of cancer care, from diagnosis to treatment to long-term follow-up. This symptom affects 70% to 100% of cancer patients.8 Fatigue is also experienced by cancer survivors, and when strict ICD-10 diagnostic criteria are used, the prevalence of fatigue among survivors ranges from 17% to 21%.6

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CAUSES AND PATHOPHYSIOLOGY OF CRF

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Fatigue can be due to the patient's malignancy, cancer treatment, or any of a multitude of comorbid conditions. In some patients, fatigue is the presenting symptom of the malignancy. For example, a patient with a hematologic malignancy might have significant anemia resulting in the sensation of fatigue. In other patients, fatigue is related to the cancer treatment. For example, patients receiving high-dose chemotherapy can experience fluctuations in fatigue, with worsening of the fatigue as their blood counts reach their nadir and subsequent improvement as the counts recover.9 Patients receiving radiotherapy may experience worsening fatigue as their treatment progresses.10 As for the effects of surgery on fatigue, there are limited data available at this time. Patients receiving biologic response modifiers can experience severe fatigue, and it can affect their treatment regimen.11 Finally, fatigue can be related to the presence of comorbid conditions. The list of medical conditions that are associated with fatigue is quite long and includes endocrine disorders such as hypothyroidism, sleep disorders, coronary artery disease, metabolic abnormalities, depression, and anxiety, to name a few. Fatigue can also be caused by medical therapy, and thus it is important to review patients' medication lists.

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Research into the pathophysiology of CRF is in its infancy. There are currently several proposed mechanisms for this symptom. The theory of serotonin dysregulation proposes that CRF is caused by an increase in brain serotonin levels in localized regions of the brain and ...

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