Guideline sources The following summarized guidelines for the evaluation and management of cancer-associated fatigue are prepared by our editorial team based on guidelines from the Canadian Association of Psychosocial Oncology (CAPO 2017) and the American Society of Clinical Oncology (ASCO 2014). 1 2 3 3 4 5 Definition Cancer-associated fatigue is a distressing, persistent, subjective sense of physical, emotional, and/or cognitive tiredness or exhaustion associated with cancer and/or cancer treatment, which is non-proportional to recent activity and interferes with usual functioning. 3 Epidemiology Cancer-associated fatigue is multifactorial and involves medical factors (comorbidities, medications, nutritional disorders), psychosocial factors (mood disturbance), behavioral factors (physical deconditioning), and biological factors (anemia, cytokine dysregulation, hypothalamic-pituitary- adrenal axis dysregulation, 5-HT neurotransmitter dysregulation, and alterations in ATP and muscle metabolism). 3 Disease course https://web.pathway.md/diseases/rec391juXSvd5ZRvX 1/5 6/29/23, 3:24 AM Cancer-associated fatigue Pathway Disease course Cancer-associated fatigue and exhaustion is often accompanied by pain, mood changes, sleep disturbances, lack of appetite, decreased activity, and reduced quality of life and performance. 4 Prognosis and risk of recurrence Cancer-associated fatigue is associated with increased all-cause mortality in patients with solid tumors. 5 Guidelines 1. Screening and diagnosis Indications for screening: As per CAPO 2017 guidelines, use a valid quantitative measure to screen for the presence of cancer-related fatigue at specified times or as clinically indicated. E As per ASCO 2014 guidelines, routinely screen patients with cancer for the presence of fatigue from the point of diagnosis onward, including after completion of primary treatment. E 2. Diagnostic investigations Clinical assessment: As per CAPO 2017 guidelines, complete a focused assessment of fatigue and possible medical causes in patients in whom fatigue screen is positive (score 2 on a 0-10 NRS). E As per ASCO 2014 guidelines, perform a focused fatigue history, evaluate disease status, and assess for treatable contributing factors. E Laboratory evaluation: consider further laboratory evaluation based on presence of other symptoms and onset and severity of fatigue. E 3. Medical management General principles: As per CAPO 2017 guidelines, attend to contributing factors and/or refer for further specialist evaluation. E As per ASCO 2014 guidelines, address all treatable factors contributing to cancer-associated fatigue (e.g., pain, depression, anxiety, emotional distress, sleep disturbance, nutritional deficit, activity level, anemia, medication adverse effects, and comorbidities). E Pharmacological agents: As per CAPO 2017 guidelines, insufficient evidence to recommend pharmacological agents for fatigue at any stage of disease. I https://web.pathway.md/diseases/rec391juXSvd5ZRvX 2/5 6/29/23, 3:24 AM Cancer-associated fatigue Pathway As per ASCO 2014 guidelines, consider initiating psychostimulants such as methylphenidate and other wakefulness agents including modafinil to manage fatigue in patients with advanced disease or those receiving active treatment. However, there is limited evidence of their effectiveness in reducing fatigue in patients after active treatment who are currently disease free. E Assessment of treatment response: observe and reevaluate patients treated for fatigue on a regular basis to determine whether treatment is effective or needs to be reassessed. E 4. Nonpharmacologic interventions Physical activity: As per CAPO 2017 guidelines, advise all patients to engage in moderate-intensity physical activity for at least 30 minutes on five or more days of the week, if not medically contra- indicated. E As per ASCO 2014 guidelines, actively encourage all patients to engage in a moderate level of physical activity after cancer treatment (150 minutes of moderate aerobic exercise per week, such as fast walking, cycling, or swimming; 2-3 sessions of strength training per week, such as weight lifting). E Psychosocial interventions: As per CAPO 2017 guidelines, preliminary evidence suggests that mindfulness-based interventions are likely to improve fatigue. E As per ASCO 2014 guidelines, consider CBT/behavioral therapy as it can reduce cancer-related fatigue in post-treatment survivors. E Alternative treatments: As per CAPO 2017 guidelines, insufficient evidence to recommend herbal medicines or acupuncture for treatment of fatigue. I As per ASCO 2014 guidelines, some evidence supports that yoga and acupuncture can reduce fatigue in cancer survivors. E Micronutrient suppplements: insufficient evidence to assess the effectiveness of the impact of supplements, such as ginseng, vitamin D, and others, on cancer-related fatigue. I 5. Patient education General counseling: As per CAPO 2017 guidelines, provide routine patient education about fatigue self-management in all patients. E As per ASCO 2014 guidelines, offer specific education about fatigue to all patients after treatment (e.g., information about the difference between normal and cancer-related fatigue, persistence of fatigue after treatment, and causes and contributing factors). E https://web.pathway.md/diseases/rec391juXSvd5ZRvX 3/5 6/29/23, 3:24 AM Cancer-associated fatigue Pathway 6. Follow-up and surveillance Indications for specialist referral: As per CAPO 2017 guidelines, promote access to multi-component, group psycho-education programs targeted at teaching self-management techniques. E As per ASCO 2014 guidelines, recognize when referral to an appropriately trained professional (e.g., a cardiologist, an endocrinologist, a mental health professional, or an internist) is needed. E Clinical findings Symptoms Past medical history Depression BMT Diarrhea Biologic therapy Fatigue doesn't come from activity or exertion Exposure to radiation therapy Hypothyroidism Fatigue is not relieved by rest or sleep Medications Tumor-induced "hypermetabolic" state Fatigue often described as "paralyzing" Heartburn Hematological findings Impaired or absent taste Anemia Insomnia Mouth or nose sores Nausea Pain Provoked by stress Vomiting Anthropomorphic exam Malnutrition References 1. Bower JE, Bak K, Berger A et al. Screening, assessment, and management of fatigue in adult survivors of cancer: an American Society of Clinical oncology clinical practice guideline adaptation. J Clin Oncol. 2014 Jun 10;32 17 1840 50. Open 2. Pearson EJM, Morris ME, McKinstry CE. Cancer related fatigue: implementing guidelines for optimal management. BMC Health Serv Res. 2017 Jul 18;17 1 496. Open 3. Julienne E Bower. Cancer-related fatigue mechanisms, risk factors, and treatments. Nat Rev Clin Oncol. 2014 Oct;11 10 597 609.2014 Oct;11 10 597 609. Open https://web.pathway.md/diseases/rec391juXSvd5ZRvX 4/5 6/29/23, 3:24 AM Cancer-associated fatigue Pathway 4. Markus Horneber, Irene Fischer, Fernando Dimeo et al. Cancer-related fatigue: epidemiology, pathogenesis, diagnosis, and treatment. Dtsch Arztebl Int. 2012 Mar;109 9 161 71; quiz 172.2012 Mar;109 9 161 71; quiz 172. Open 5. Salome Adam, Lonneke V van de Poll-Franse, Floortje Mols et al. The association of cancer-related fatigue with all-cause mortality of colorectal and endometrial cancer survivors: Results from the population-based PROFILES registry. Cancer Med. 2019 Jun;8 6 3227 3236.2019 Jun;8 6 3227 3236. Open 6. American Academy of Neurology. Choosing Wisely AAN recommendations. Choosing Wisely. 2015. Open 7. Julienne E. Bower. Cancer-related fatigue: Mechanisms, risk factors, and treatments. Nat Rev Clin Oncol. 2014 Oct; 11 10 597 609. Open 8. Salome Adam, Lonneke V. van de Poll Franse, Floortje Mols et al. The association of cancer related fatigue with all cause mortality of colorectal and endometrial cancer survivors: Results from the population based PROFILES registry. Cancer Med. 2019 Jun; 8 6 3227 3236. Open https://web.pathway.md/diseases/rec391juXSvd5ZRvX 5/5