NCCN Categories of Evidence and Consensus
Category 1: Based upon high-level evidence, there is uniform NCCN consensus that the intervention is appropriate.
Category 2A: Based upon lower-level evidence, there is uniform NCCN consensus that the intervention is appropriate.
Category 2B: Based upon lower-level evidence, there is NCCN consensus that the intervention is appropriate.
Category 3: Based upon any level of evidence, there is major NCCN disagreement that the intervention is appropriate.
All recommendations are category 2A unless otherwise noted.
Clinical trials: NCCN believes that the best management for any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.
NCCN 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.”1 Fatigue is a common symptom in patients with cancer and is nearly universal in those receiving cytotoxic chemotherapy, radiation therapy, bone marrow transplantation, or treatment with biological response modifiers.2-4 According to a survey of 1569 patients with cancer, the symptom is experienced by 80% of individuals who receive chemotherapy and/or radiotherapy.5,6 Cancer survivors report that fatigue continues to be a disruptive symptom after treatment ends,7-14 with studies showing that 17% to 29% of cancer survivors experience persistent fatigue for years after the completion of active therapy.15,16 Persistent cancer-related fatigue affects quality of life, because individuals become too tired to fully participate in the roles and activities that make life meaningful.9,17 Disability-related issues are also relevant for cancer survivors, because obtaining or retaining disability benefits from insurers is often difficult for patients with cancer-related fatigue. Identification and management of fatigue remains an unmet need for many cancer survivors.
The specific mechanisms involved in the pathophysiology of cancer-related fatigue are unknown. Proposed mechanisms include proinflammatory cytokines, hypothalamic-pituitary-adrenal axis dysregulation, circadian rhythm desynchronization, skeletal muscle wasting, and genetic dysregulation.18-23 Several studies have focused on the cause of fatigue, especially in cancer survivors with no evidence of active disease, and have suggested that persistent immune system activation and chronic inflammatory processes may be involved.7,24-26 Evidence supporting these mechanisms is limited.
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Ruffer JU, Flechtner H, Tralls P et al.. Fatigue in long-term survivors of Hodgkin’s lymphoma; a report from the German Hodgkin Lymphoma Study Group (GHSG). Eur J Cancer 2003;39:2179–2186.
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Wang XS, Zhao F, Fisch MJ et al.. Prevalence and characteristics of moderate to severe fatigue: A multicenter study in cancer patients and survivors. Cancer 2014;120:425–432.
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Berger AM, Wielgus K, Hertzog M et al.. Patterns of circadian activity rhythms and their relationships with fatigue and anxiety/depression in women treated with breast cancer adjuvant chemotherapy. Support Care Cancer 2009;18:105–114.
Bower JE. Cancer-related fatigue: links with inflammation in cancer patients and survivors. Brain Behav Immun 2007;21:863–871.
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McNeely ML, Campbell KL, Rowe BH et al.. Effects of exercise on breast cancer patients and survivors: a systematic review and meta-analysis. CMAJ 2006;175:34–41.
McNeely ML, Courneya KS. Exercise programs for cancer-related fatigue: evidence and clinical guidelines. J Natl Compr Canc Netw 2010;8:945–953.
Speck RM, Courneya KS, Masse LC et al.. An update of controlled physical activity trials in cancer survivors: a systematic review and meta-analysis. J Cancer Surviv 2010;4:87–100.
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