Cancer-Related Fatigue – Clinical Evaluation Scales and Interventions: A Systematic Review

Cancer-related fatigue (CRF) and its prevalence

As per the National Comprehensive Cancer Network, ‘Cancer-related fatigue is 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 it interferes with usual functioning.’^[7] In the words of Cella et al. (1998), ‘Cancer- related fatigue is the subjective state of overwhelming, sustained exhaustion and decreased capacity for physical and mental work that is not relieved by rest.’^[8] A patient’s level of fatigue varies during the day, according to their treatment, and follows a pattern related to the course of the day. Cancer patients and cancer survivors cite fatigue as the most disturbing and disabling of symptoms.^[7]

Patients with cancer report frequent fatigue as a symptom of their disease.^[8-10] Among patients undergoing chemotherapy or radiation therapy, fatigue ranked highest along with pain (48%) and nausea/vomiting (48%) as distressing symptoms.^[10-12] Fatigue was identified as the top-rated; high ranked, and the most concerning symptom among patients with advanced cancers (10 out of 11 types of various cancers).^[13] Thus, the variability in fatigue prevalence among cancer types is high, ranging from 25% to 100%.^[14,15] Period before, during, and after treatment has also played a major role in the experience of fatigue by the patients.^[16,17]

Although a most prevalent symptom, fatigue from cancer is one of the understated, underestimated, and undermanaged symptoms which are least taken into consideration by the health professionals while managing cancer patients. Fatigue associated with cancer has a detrimental effect on the quality of life, adherence to treatment, productivity, or efficiency. Hence, this review article highlights the importance of clinical evaluation and appropriate intervention for managing fatigue. The prime objective of this review was to explore the different scales utilised for the screening and assessment of fatigue associated with cancer. The second objective was to identify the various non- pharmacological and pharmacological interventions which aid in the mitigation of fatigue. Therefore, this systematic review included all types of research article to provide comprehensive evidence about the scales and multiple interventions options for CRF.

Data sources and search strategy

A broad systematic search of two separate databases, that is, PubMed and Google Scholar was carried out to recognise all the available and relevant full-text articles dating from 2000 to December 2020. The key words such as ‘Scales,’ ‘Tools,’ ‘Assessment,’ ‘Interventions,’ ‘Management’ and ‘Cancer-related Fatigue’ were merged using the Boolean operators (‘AND’ and ‘OR’). [Table 1] represents the search combination of keywords and Medical Subject Heading (MeSH) terms. Hand searches of books and grey literature of the relevant articles were also conducted. This review aimed to examine and summarise the evidences related to CRF scales and interventions.

Eligibility criteria

Inclusion criteria for the articles are as follows:

1. Populations: Adult patients who were more than 18 years undergoing any treatment for cancer

2. The outcome of interest: Scales or tools for the evaluation and interventions for fatigue management

3. Type of research articles: All types of research articles including the grey literature

4. Articles published only in the English language.

Exclusion criteria

1. Research articles involving paediatric population

2. Research studies involving participants without cancer

3. Articles published in other languages other than English

4. Research protocols and case reports.

Methodological quality assessment of articles

The methodological quality and risk of bias of the included articles were determined by Joanna Briggs Institute critical appraisal tools, a quality assessment tool. Different critical appraisal tools were used for different types of articles such as tool development studies, RCTs, systematic reviews or reviews, or opinions. Ratings are made as ‘Yes,’ ‘No,’ ‘Unclear’ or ‘Not/Applicable’ for the domains of quality appraisal tools.^[19]

Data synthesis (characteristics of included articles) related to scales for the assessment of CRF

The extracted data were synthesised under the following headings such as:

• Details of publication: Author’s last name and year of publication

• Types of the research article

• Sample characteristics: Type of cancer

• Outcome measurement: Type of scale which assessed the CRF and the interventions.

A qualitative review was done by the reviewers based on the data extracted and presented the attributes of the included articles condensed in the form of narrative synthesis in [Tables 2 and 3].

Clinical evaluation scales used for measuring CRF

This systematic review revealed two types of scales, namely unidimensional and multidimensional scales that is, four single-item unidimensional scales, six multiple item unidimensional scales, and 13 multidimensional scales from different types of research articles. The research articles comprised five review articles, four research articles related to psychometric properties, two systematic reviews, and one grey literature. Before, during and after treatment, it is recommended that cancer-related fatigue be assessed at regular intervals.

Unidimensional scales deal with the examination of fatigue in terms of severity and its existence. Different single-item unidimensional scales are as follows:

Single-item unidimensional scales

1. NCCN fatigue intensity scale – National Comprehensive Cancer Network developed this fatigue severity screening tool (NCCN, 2018). It aids to screen the severity of fatigue by rating among cancer patients at regular intervals on a scale of 0–10. The score of ‘0’ represents an absence of fatigue and 10 represents worst fatigue. According to this scale, 0–3, 4–6, and 7–10 indicate no or mild fatigue, moderate fatigue, and severe fatigue, respectively^[7]

2. The fatigue intensity scale – This scale is similar to NCCN fatigue intensity scale. The score ‘0’ depicts no fatigue and score 10 depicts overwhelming fatigue. It is a single-item and single dimension scale used for the screening of fatigue in cancer patients. It has strong criterion validity estimates and strong concurrent validity with the piper fatigue scale revised^[20]

3. Rhoten fatigue scale – it can be recommended for screening purposes. The dimension of this scale is severity. A score of 0 represents not being tired or full of energy and 10 represents totally exhausted^[20]

4. Visual analogue scale – Visual analogue scale for fatigue (VAS-F) is a 10 cm scale of the horizontal line (0–100 mm) for the assessment of the severity of fatigue. The score ‘0’ indicates ‘I don’t feel tired’ and score 10 indicates ‘I feel totally exhausted.’ This scale is predominantly tested in cancer patients of Switzerland and Germany. Similar to other VAS, it is also recommended to consider the measurement characteristics while using it for research screening and clinical practice.[^20]

There are numerous multiple item unidimensional scales [Table 4] available for the assessment of fatigue.^[20-25]

Multidimensional scales are the scales which measure the impact of fatigue on various domains such as physical, psychological, emotional, social, and affective functioning of patients with cancer. Different multidimensional scales used for the evaluation of fatigue are depicted in [Table 5].^{[20-23,25-29]}

Interventions for CRF

Regarding the interventions, this systematic review identified various non-pharmacological and pharmacological approaches for the treatment of fatigue. Out of 29 research articles related to interventions, there were seven review articles, four systematic reviews and meta-analysis, 10 RCTs, one experimental research, two pilot study, one book, one prospective research study and three grey literature. Interventions for fatigue can be grouped into non-pharmacological and pharmacological measures. The non-pharmacological interventions are as follows:

Exercise

Exercise intervention has a beneficial impact on physiological process as well as quality of life. Exercise has a direct impact on cardiorespiratory status, promotes the well-being and reduces chances of mortality related to cancer. It is recommended to undergo 150 min of moderate-intensity exercise or 75 min of vigorous intensity exercise in a week. Exercise can be walking, cycling, running, bowing or any aerobic exercises. It should be planned, spread throughout the week for short intervals of 10 min.^[30-32]

Complementary therapies

The present-day yoga form involves the combination of physical activity, yoga asanas and mindfulness. Patients with cancer are able to manage cancer-related fatigue more effectively through yoga and enhance their quality of lives.^[33,34] ‘Yoga is considered as the viable therapeutic intervention for CRF.’^[33,34] Mindfulness-based stress reduction programme is a form of complementary therapy that helps to improve the health and well-being of the individuals. In the 1970s, Kabat-Zinn developed MBSR programme.^[33] Majority of complementary therapies are found to have a beneficial influence on fatigue and the patients’ quality of life. Complementary therapies such as aromatherapy, acupressure and acupuncture, foot soak with reflexology, massage and Reiki therapy are providing promising results in treating CRF, but limited studies are available for developing the frame of evidence with greater significant results.^[35-39]

Nutritional intervention

One of the contributing factors for the CRF is malnutrition. Anorexia cachexia syndrome is usually experienced by the cancer patients and it predisposes to malnutrition in them. Adverse effects associated with treatments include nausea, vomiting, stomatitis, diarrhoea and mucositis which contribute to malnutrition and aggravate the fatigue associated with cancer. Dietary counselling aided in the reduction of fatigue rather than providing the protein supplements to cancer patients as stated by Ravasco et al.^[40] It not only increased the nutritional status of patients but also improved the CRF.^[35,40]

Educational interventions (psychoeducation)

Education intervention combined with psychological support is termed as psychoeducation. It has a positive influence on fatigue, its pattern, self-management, supportive positive coping (counselling) and coordinated care. This intervention aids in enhancing the motivation and empowering the patients for self-care, positive coping and provides opportunity to improve the self-efficacy and emotional control. Supportive counselling promotes social support with assistance in coping.^[33,41]

Cognitive behavioural therapy

Fatigue associated with cancer can be managed effectively by cognitive behavioural therapy by indirectly acting on the concurrent symptoms such as sleep problems, pain and depression. Randomised controlled trials in metastatic breast cancer population demonstrated that CBT administered for depression significantly resulted in the reduction of CRF.^[33,41,42]

Sleep therapy

One of the persistent causes of fatigue is sleep disorders which can be hypersomnia or insomnia. It results in reduced nocturnal quality of sleep and ultimately leads to fatigue throughout the day. Providing guidance on sleep hygiene such as consistent time of sleep and rise in every morning, reduced time spent in the bed and limited day time naps is the aspects of sleep hygiene. The sleep therapy incorporates sleep hygiene measures and contributes in minimising fatigue.^[41,43]

Polarity therapy/energy therapy

Dr. Randolph Stone developed an innovative energy therapy commonly known as Polarity therapy in the year 1947. It incorporates the balance of energy field within the organisms and enhances the health and well-being of the individual. Researchers evaluated the significance of polarity therapy in alleviating fatigue and found it to be useful among survivors of breast cancer. More number of RCTs are needed to demonstrate the effectiveness of energy therapy.^[41,44]

Bright white light therapy

Bright white light therapy is a therapeutic intervention in which very high fluorescent light is emitted from light box and patients are exposed to it. It is available for purchase and can be used at home. It is commonly deployed for the treatment of sleep and mood disorders in elderly group and in the general public. Breast cancer patients undergoing chemotherapy are exposed to bright white light therapy and a favourable outcome was seen in CRF. Ideal time of administering BWLT is early morning for the duration of 30–90 min. It is recommended for the patients experiencing fatigue during active treatments.^[7]

Restorative therapy

Restorative therapy is the use of restorative activity aids in managing the mental or attentional fatigue. It was developed by Kaplan. Engagement in activities such as music therapy and natural environment helps in the restoration of feeling of mental peace. Enjoying the endeavour from the initiation and focus on new assignment and challenges is also a part of restorative therapy.^[33] More research studies are recommended to identify the effectiveness of restorative therapy for fatigue management with higher statistical power.

Anthroposophical medicine

Anthroposophical medicine is integrative medicine which is a type of alternative system of medicine. It was originated in the early 1920s by Rudolf Steiner and Ita Wegman. It comprises art therapy (painting or drawing), music therapy, sculptures, therapeutic speech and eurythmy therapy.^[45-47]

Eurythmy therapy is an expressive art movement which attempts to reintegrate the components body, soul and spirit and thereby enhance the health-related life functions.^[48] Therapeutic speech also claims to improve the fatigue, as there is no sufficient research evidence to support eurythmy therapy and therapeutic speech for its utilisation in clinical practice.^[47]

Pharmacological management for CRF

There are several pharmacological interventions for CRF. Different pharmacological agents which are found to be effective through clinical trials include ATP infusion,^[49] bupropion sustained release,^[50-52] donepezil,^[53] methylphenidate, modafinil, steroids,^[53] L-carnitine,^[54] high dose Vitamin C,^[55] paroxetine,^[56] and recombinant human erythropoietin.^[57,58]