Clinical updates in cancer-related fatigue in palliative care settings—a scoping review

Introduction

Cancer-related fatigue (CRF) is defined as a sense of exhaustion related to cancer or cancer treatment affecting normal functioning. The persistent exhaustion level is not proportional to the activity level and is not relieved by proper rest (1). It is a common symptom affecting patients with the majority of cancers with a significant impact on the overall quality of life. The prevalence of CRF ranges from 15% to 99% that depends on the patient and the fatigue assessment tool used (2). The main reasons include the effect of cancer itself or the side effect of the treatment option administered to the patient. Chemotherapy is responsible for fatigue in around 90% of the patients while radiotherapy causes fatigue in around 80% (3). CRF has a complex and multifactorial origin, making it difficult to pinpoint specific causes, as they often co-exist and are interlinked with each other (4,5).

In addition to factors like the cancer itself or the side effect of the cancer treatment, the other factors that play a crucial role in the development of CRF include disturbed sleep, lack of physical activity, psychological or behavioral reaction to the diagnosis or treatment, physical, and mental health conditions like depression (6). The current landscape of treatment options for CRF include pharmacological, non-pharmacological and complementary and alternative medicine (CAM) methods. It is essential to note that the effective management of CRF is still undermined due to the belief that fatigue is an unavoidable and inevitable aspect of cancer and its treatment. This belief is shared by healthcare professionals, patients and caregivers that contributes to CRF being under reported and under addressed.

Rationale and knowledge gap

Inconsistencies have been noted across evidence-based guidelines for CRF, largely due to variations in how the evidence is synthesized and the methods used to formulate recommendations. These discrepancies pose challenges to the practical application of such guidelines in palliative clinical settings. There has been a growing interest in synthesizing findings to determine more definitive best practices for CRF. However, there are limited reviews that have highlighted all the treatment domains for CRF in palliative care in recent years. Therefore, there is a need for collating the findings and recommendations given in the last 5 years for the diagnosis and management of CRF. There is a gap in knowledge regarding integrated management for CRF since many studies have reported individual interventions. For effective management there is a need of a unified approach addressing all domains like screening, pharmacological, non-pharmacological, and complementary methods.

Objectives

The given scoping review aims to map the existing evidence on the management of CRF in palliative care settings and to identify and explore the recent clinical updates related to screening, diagnosis, and management. We present this article in accordance with the PRISMA-ScR reporting checklist (available at https://apm.amegroups.com/article/view/10.21037/apm-25-50/rc).

Methods

Search design and search strategy

This scoping review aims to identify key themes and map recent updates, and clinical practices related to CRF in palliative care settings. Databases including PubMed, Embase, Cochrane, Medline were used for our search, and the articles were imported to Covidence. The search included publications from January 2020 to March 2025. CRF management has evolved in recent years, so in order to reflect the latest advancements and practical recommendations this timeframe was chosen. The search string included a combination of keywords such as “cancer”, fatigue”, “palliative care”, “end of life care”, “hospice”, “supportive care”, “advanced cancer”, “diagnosis”, “workup”, “management”, and “assessment”.

Subsequently, a flow diagram was created to report the number of studies identified, screened, included, and excluded along with reasons for exclusion (depicted in Figure 1).

Figure 1 PRISMA 2020 flow diagram. CRF, cancer related fatigue.

Inclusion and exclusion criteria

Studies that fulfilled the following criteria were included: (I) adult cancer patients that experienced CRF; (II) patients receiving palliative care services in any of the given settings like outpatient, home-based, hospital-based and hospice; (III) observational studies, randomized control trials (RCTs), systematic reviews, meta-analyses, and narrative reviews; (IV) studies that focused on diagnosis, assessment tools, screening tools, pharmacological, non-pharmacological, complementary and interventions.

The exclusion criteria for this study are: (I) pediatric patients experiencing CRF; (II) studies that focus on general fatigue rather than CRF specifically; (III) research protocols, and conference abstracts; (IV) articles published in languages other than English; (V) studies with no full text available.

Study selection

Articles obtained from the various databases were uploaded to Covidence and duplicate studies were eliminated. In the first phase, two independent reviewers (Z.Y.M., S.M.) screened titles and abstracts, followed by conflict resolution by discussion between the reviewers (Z.Y.M., S.M.). Similarly, full text screening was carried out and disputes regarding the potential inclusion of the article was resolved by a discussion between the 2 reviewers (Z.Y.M., S.M.).

Data collection and synthesis

Data was extracted from the studies, and they were analysed thematically. Four common themes were identified from the extracted studies namely, diagnostic and assessment tools, non-pharmacological, pharmacological, and complementary interventions for CRF.

Results

A total of 4,444 articles were identified through database searches. After removing duplicates and screening titles and abstracts, 77 articles were retained for full-text review. The study designs of the included articles were systematic reviews (n=4), systematic reviews with meta-analyses (n=24), randomized controlled trials (n=6), narrative reviews (n=7), umbrella reviews (n=5), and clinical update guidelines (n=7). The distribution of the studies has been depicted in Figure 2.

Figure 2 Histogram depicting the distribution of studies by study design and publication year.

Studies mainly focused on fatigue in patients diagnosed with cancer at various stages, with an additional focus on palliative care and cancer survivors. The included studies focused on various aspects of interventions, including pharmacological, non-pharmacological and complementary therapies. The studies highlighting the interventions have been represented in Figure 3.

Figure 3 Distribution of studies by type of intervention for cancer-related fatigue. CBT, cognitive behavioral therapy; CBT-AP, cognitive behaviour therapy integrated with activity pacing.

Screening and assessment tools for CRF

The diagnosis of CRF can be as heterogenous and multidimensional as the cancers that underly it. A total of 114 articles were reviewed by Clinical Practice Guideline (CPG) on screening and assessment of CRF. The findings revealed that no CRF screening or assessment tool has been validated for all cancer types and different tools should be used in different cancers. Additionally, the timing during the care continuum, divided into active treatment phase, immediate posttreatment phase and long-term survivorship, determines the appropriate tool to be used (7).

The subjective nature of fatigues sets self-report as the primary diagnostic method with more than 50 different self-report questionnaires making the result comparison across clinical settings and studies difficult, limiting consistency and cross-population analysis (8). Various studies have identified the validated screening and assessment tools for CRF as shown in Table 1.

Screening for CRF

Ten different screening tools were evaluated to categorize them as level A rating and level B rating, which is a demonstration of high-good quality evidence of their validity and reliability. Level A screening tool constitutes the European Organization of Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), which is a 30-item quality of life questionnaire on various symptoms. The MD Anderson Symptom Inventory (MDASI) questionnaire is a level B screening tool which is a 13-item questionnaire assessing the severity and effect of a multitude of cancer related symptoms. While the former is recommended to be used during the active treatment phase, the latter can be used any time across the care continuum. Another easily implementable screening tool is the Distress Thermometer and the One-Item Fatigue Scale that are being used widely in the clinical setting (8). The National Comprehensive Cancer Network (NCCN) recommends using a single item screening instrument for all cancer patients aged more than 12 years. Single-item screens provide quick, meaningful cut offs but should be used with caution, as they lack a full assessment of CRF’s physical, emotional, and cognitive aspects (10).

The European Society for Medical Oncology (ESMO) guidelines recommend using a 10-point numerical rating scale (NRS) for fatigue screening. If the NRS is at or above 4, a diagnostic assessment should be sought through focused fatigue history, examination, an evaluation of the status of the underlying malignant disease, a mental status examination and laboratory blood tests. Use of other CRF assessment tools could be used but no specific tool was clearly advocated (16).

Assessment of CRF

The multi-dimensionality of CRF includes physical, emotional and cognitive aspects, and the identification of the most important contributing factors is crucial in determining the next steps. Of the ten different assessment tools evaluated by the CPG mentioned previously, level A and B rating was given to three and five tools, respectively. Important considerations to determine the appropriate tool include patient language, point of care along the care continuum and type of cancer. It is important to understand the three assessment tools recommended for use. Functional Assessment of Chronic Illness Treatment-Fatigue (FACIT-F) is a 41-item questionnaire covering multiple domains with a 13-item fatigue specific subscale. The second tool is the Piper Fatigue Scale-Revised (PFS-R), which is 22-item questionnaire for assessing the current level of fatigue experienced by the patient. The main domains that are covered include behavioural, affective, sensory, and cognitive/mood symptoms. A third tool which is essential to note is the Patient-Reported Outcome Measurement Information System (PROMIS) fatigue tool which offers six short forms, indicated by a number assessing fatigue over the past week (9).

Despite the need to assess CRF in all cancer patients, research on assessment tools has been more concentrated on the more common cancer types including breast, prostate, colorectal, and lung cancer. Interestingly, all CRF assessment tools receiving level A and B rating have been validated in breast, colorectal and lung cancer patients, while their validation in brain, and multiple myeloma is still pending. A systematic review specifically looking at the psychometric properties of CRF tools in breast cancer patients found a total of nine tools, of which five were classified as being level A or B rating in the CPG [Brief Fatigue Inventory (BFI), FACIT-F, Fatigue Symptom Inventory (FSI), Multidimensional Fatigue Inventory (MFI), PFS-R]. Consistent with what was reported in the CPG, based on their psychometric properties PFS-R and FACIT-F scales were both considered of having good reliability and validity in breast cancer patients (9).

Non-pharmacological intervention

Non pharmacological techniques are regarded as the first line options for CRF management. Studies have suggested that they have a strong correlation with an improved quality of life and overall functioning (17). It encompasses many techniques which include physical activity, cognitive behavioural therapy (CBT), psychosocial, mindfulness-based interventions, and sensory therapy that have shown promising results with respect to CRF (18,19) (that have been described in Table 2). With a plethora of these techniques, it is essential to consider that there is variable efficacy of these techniques and identifying the appropriate technique or combination of techniques is crucial to ensure optimal CRF management. Various studies have identified these methods that can be used for CRF as shown in Table 2.

Exercise

Exercise has gained recognition as an important non-pharmacological option for CRF management. It promotes endorphin release that helps in pain modulation and improves cardiovascular function, muscle strength, and sleep quality, all of which are affected in patients with CRF (26). Moreover, regular physical activity can be protective against the inflammatory and metabolic changes that are seen in CRF (37). Belloni et al. demonstrated the effectiveness of different exercise types in comparison to no exercise with a standardized mean difference (SMD) of −0.32 [95% confidence interval (CI): −0.42 to −0.23], promoting the use of exercise for CRF management (21). Zuo et al. also suggested that moderate-intensity aerobic exercise done at least thrice a week for a minimum of 12 weeks can cause a marked reduction in fatigue levels (17). The benefits get amplified when combined with resistance training two to three times per week (25). In older and more frail patients, this can help maintain functional status and minimize needs for personal care at advanced stages of illness (38,39). Contrastingly, Poort et al. evaluated a graded exercise program and found no statistically significant difference at the end of 14 weeks between the intervention and no intervention group (24). American Society of Clinical Oncology (ASCO) came up with recommendations focusing on aerobic and resistance exercise to reduce CRF and improve overall patient well-being (28). Experts advocate exercising several times a week with an aim of reaching 60–85% of the maximum heart rate (26). However, with the variability across clinical trials, the use of exercise therapy should depend on the individual patient needs, overall clinical condition, and functional status (40).

CBT

CBT functions by identifying and restructuring maladaptive thoughts, regulating emotions, and developing effective coping strategies (18). They provide symptom relief by addressing the underlying psychological distress and behavioural habits. Trials found the patients receiving CBT for CRF to benefit significantly compared to those receiving usual care (62% vs. 31%) with effects lasting (24). On similar lines, benefits with CBT were also observed in narrative review, although the strength was moderate to low across studies (23). Similarly, Yuan et al. showed a positive impact of CBT on CRF when used in advanced cancer patients in their network meta-analysis (27).

On the contrary, a trial comparing a specific CBT intervention which is managing cancer and living meaningfully (CALM), with supportive psycho-oncological counselling found no difference in CRF management between the 2 groups (25). Acceptance and commitment therapy (ACT), a specific type of CBT was also studied wherein four brief telephone sessions were carried out and there was no improvement reported in CRF (20). This highlights the importance of delivery method and patient selection for CBT. Delivery modes for CBT include individual or group sessions conducted offline, online or via telephone by providers, including psychologists, social workers, nurses and doctoral trainees (23). ASCO guidelines recommend the use of CBT with or without hypnosis using web-based or in-person sessions to manage CRF in advanced cancer patients. (28). A standard method for CBT intervention recommended by Zuo et al. is to conduct weekly 60-minute face-to-face CBT sessions over 6 to 12 weeks which can be incorporated as a standard regimen (17).

Mindfulness-based therapy

Mindfulness based interventions (MBI) including mindfulness-based stress reduction (MBSR) constitute body scan meditation, breath awareness, walking meditation, and mindful movement (18). Pro-inflammatory cytokines like interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-α) are decreased by MBSR, resulting in reduction of systemic inflammation and ultimately CRF (27). These therapies aim to improve present-moment awareness, and enable patients to cope with psychological stressors more effectively (22). Belloni et al. demonstrated the continued benefit of the MBI therapy at 4 weeks to 6 months post-intervention with SMD of −0.55 in comparison to no intervention with the effect lasting for up to 3 months (34). An 8-week MBSR program involving weekly group sessions and 45 minutes of daily self-directed training was also effective in treating CRF (18). MBSR was also found to be effective for CRF reduction in active breast and lung cancer patients (22,32). However, a trial conducted by Sheikhzadeh et al. observed that mindfulness based cognitive therapy (MBCT) is not associated with a significant decrease in CRF compared to wait-list control (P=0.10) (30). McCloy et al. also reported that that intervention length (<8 vs. 8 weeks) had no significant difference in CRF reduction (29). The use of in-person or web-based MBSR was strongly recommended by ASCO for alleviation of CRF during and after cancer treatment (28). This recommendation endorses the importance of MBI as a non-pharmacological therapy for CRF management.

Psychological interventions and sensory therapies

Various interventions like educational programs, counselling, and supportive therapies encompass psychological intervention that help treat CRF by adjusting emotions, enhancing coping ability, and promoting mental and physical health. They attenuate the emotional burden and instill psychological resilience in patients (26). Internet based self-management programs were found to be beneficial in significantly improving CRF in a meta-analysis that included 13 RCTs (23). Similarly, a positive outcome was reported after using internet-delivered psychoeducation interventions through text messaging for various cancer types, including breast cancer (22). Weekly face to face sessions over a 6-week period was recommended based on the current evidence either individually, or in a group that were either online or offline. The CRF management techniques include encouraging emotional sharing, discussing the impact CRF has had on their daily activities, and educating them regarding fatigue management strategies.

Sensory therapies, including art and music therapy attenuate CRF by activating the neural pathways to release endorphins, dopamine, and serotonin. They also promote emotional wellbeing and stress reduction in cancer patients. They are a valuable adjunct therapy for CRF because of it being non-invasive, cost efficient, and adaptable (18). Among hematological and gastrointestinal cancer patients, music therapy has proven to be efficacious in reduction of CRF during cancer treatment and rehabilitation (18) As for art therapy, a study conducted on advanced cancer patients receiving palliative care demonstrated that an hour-long art therapy session resulted in 36% reduction in CRF (P<0.001) (20). On the other hand, art therapy indicated initial benefits that were statistically non-significant in a review of nine RCTs conducted on breast cancer patients (23). It is crucial to make use of sensory therapies with professional guidance due to increased inter-individual variability.

Pharmacological interventions

Pharmacological interventions can be utilized when non-pharmacological methods proved to be ineffective, especially in palliative care settings (41). Pharmacological methods are employed after reversible causes have been addressed (42). The various drugs that can be used for management of CRF are corticosteroids, psychostimulants, melatonin, bupropion, donepezil, and pasireotide. Multiple studies have identified these agents for CRF as shown in Table 3.

Management of reversible conditions associated with CRF

Addressing the physiological and psychological of CRF by treating causes like anemia, depression, and sleep is essential. Anemia induced fatigue can be managed by hematopoietic agents (erythropoietin and darbepoetin) that stimulate red blood cell production (42,43). Benefits of hemopoietic agents have been specifically observed in chemotherapy induced anemia, although there are notable side effects like cancer progression and adverse central nervous system and cardiovascular effects (5,14,49). Pain control with opioids have proven to improve CRF indirectly in recent studies (32). Conditional recommendation is given for the use of hematopoietic and pain control agents for alleviation of CRF (5,14,32). Multiple trials have also shown the effectiveness of placebo in management of CRF (32,43). Direct comparison between agents is a challenge because of variability in stage of the disease and limited number of advanced cancer patients (32,43).

Corticosteroids

The various underlying mechanisms by which corticosteroids reduce CRF is the modulation of the hypothalamic pituitary adrenal (HPA) axis, inflammatory pathways, and mood enhancement (37,45,47). Corticosteroids are valuable since studies have observed elevated cytokines levels of IL-1, IL-6, and TNF-α and HPA dysfunction in patients experiencing CRF (45). Aligning with 2 other studies, Yennurajalingam et al. also noted the reduction in fatigue after 14 days of using 4 mg/day of dexamethasone (46). Methylprednisolone 16 mg taken twice a day was also proven beneficial in CRF management (16). Corticosteroids was shown to be more effective as compared to other pharmacological agents like methylphenidate, modafinil, and anti-depressants in CRF treatment by a recent meta-analysis (47). Short term corticosteroid use especially in advanced cancer settings is recommended by NCCN, European Association for Palliative Care (EAPC), and ASCO-Society for Integrative Oncology (SIO) guidelines (28,43). Even though corticosteroids have been found helpful for CRF, they have been associated with side effects including myopathy, insomnia, mood disturbances, and hyperglycemia (28,47).

Psychostimulants

Psychostimulants improve CRF by enhancing wakefulness, motivation and cognition by stimulating the central nervous system. They play a key role in targeting the physical and mental components of CRF by regulation of neurotransmitters like dopamine and nor-epinephrine (47).

Methylphenidate and dexamphetamine

The mechanism of action of methylphenidate and dexamphetamine is inhibition of reuptake of synaptic neurotransmitters like dopamine and norepinephrine that result in activation of the reticular activating system. This ultimately leads to better alertness, attention, and mood (47). A couple of meta-analysis observed a statistically significant improvement in CRF with methylphenidate (5,14). In contrast, ASCO-SIO suggested that the effectiveness of methylphenidate across different types of fatigue is limited, and patients with associated anxiety, depression, or drowsiness may receive a favourable response for CRF with the agent (28). A systematic review noted that only 3 of the 11 RCTs that were included in the study reported methylphenidate to be superior compared to placebo (43). Belloni et al. included 2 studies, one of them found a positive effect of methylphenidate on CRF reduction, while the other reported no benefit which could be due to insufficient sample size (41). ESMO guidelines were formed by reviewing 19 studies, of which 3 utilized methylphenidate and 1 used dexamphetamine. All the 4 studies observed that methylphenidate was beneficial for CRF management. Further subgroup analysis indicated that those experiencing severe fatigue may benefit more from methylphenidate (16). ASCO-SIO does not recommend using methylphenidate routinely, but a short trial may be given to patients in certain situations given its rapid onset of action and mild side effect profile (5,28).

Modafinil and armodafinil

Modafinil and armodafinil help with CRF by influencing dopaminergic pathways to increase synaptic dopamine and enhance arousal and cognitive performance by promoting wakefulness (47). These agents are not efficacious in reduction of CRF when compared to placebo as reported by multiple studies that observed no statistically significant difference (5,28,32,43). However, patients experiencing severe CRF and undergoing chemotherapy showed some improvement in fatigue with modafinil (32). ASCO-SIO guidelines do not recommend modafinil and armodafinil for routine use (28). Further trials are needed to understand if these agents can be used in patients unresponsive to other therapies who are enduring severe fatigue (32,43).

Other pharmacological agents

The other pharmacological drugs that affect the neurotransmitter systems include donepezil (a cholinesterase inhibitor), bupropion (a norepinephrine-dopamine reuptake inhibitor), and pasireotide (a somatostatin Analog). These medicines did not result in a statistically significant decrease in CRF in three RCTs. Donepezil reduced the incidence of fatigue in both groups, although it was no better than a placebo (16,32). A possible clinically relevant effect was observed with bupropion but it was not statistically significant (32). Melatonin helps with regulation of good sleep at night with the correction of circadian rhythm, and the patients wake up less fatigued (43). Although theoretically promising, melatonin has not been found to have a substantial effect on CRF in clinical investigations (28,43). None of these medicines are recommended for CRF management (28,32,43).

CAM

Non-conventional therapies including acupressure (AS), acupuncture (AT), Tai Chi, Qigong, yoga, massage, and moxibustion are a part of CAM. Various studies have identified these CAM techniques for CRF as shown in Table 4.

AS

AS stimulates multiple acupoints to promote relief of CRF and it is a non-invasive technique that has originated from traditional Chinese medicine. Manual, electro, and auricular AS are the various types of AS. HPA axis activation, endorphin release, and cytokine modulation are the different neuroendocrine and immune mechanisms that AS targets to alleviate CRF (54). The efficacy of AS in relieving CRF is supported by clinical evidence. Significant reduction in CRF was reported by a meta-analysis of 14 trials that recruited 776 patients, especially in female patients. Mild bruising, nausea, and muscle spasms were some of the transient adverse effects associated with the technique (61). The efficacy of true acupoint AS in CRF reduction was significantly more than sham AS with SMD of −0.28. It was further found to be better than standard care for <4 and 4–8 weeks of intervention (54). Additionally, a study demonstrated that a combination of AS and usual care had the highest probability (100%) of improvement in CRF symptoms (55). ASCO-SIO guidelines reported insufficient and heterogenous evidence for AS recommendation for CRF management during active treatment. However, based on a promising trial, conditional recommendation was given for its use in managing CRF post-treatment (28).

AT

AT, a needle-based form of acupoint stimulation, involves techniques namely electroacupuncture, auricular AT, and dry needling. Experts suggest that AT alleviates CRF by modulating T-cell activity, altering cytokine levels, and influencing neuroendocrine pathways (50). A systematic review of 13 out of 15 studies concluded that AT is likely beneficial for CRF when compared to sham AT. However, mild adverse effects such as bruising, nausea, and dizziness were also reported by participants (50). For patients with breast cancer AT indicated superiority to usual care and standard care and reflected long-term efficacy in reducing CRF but results were inconclusive compared to sham AT (54). Manual AT and point application demonstrated an 80.6% probability of reducing CRF (5). However, the evidence remains mixed. While some studies highlight its effectiveness, others ranked AT as the least effective among various complementary interventions (55). While ESMO recommends structured AT sessions, and NCCN supports its use during and after treatment, ASCO-SIO notes that current evidence remains insufficient to make definitive recommendations (16,28,52). However, AT appears to be a safe option within integrative oncology care (50). Newer evidence reveals greater efficacy, particularly post-treatment, with less benefit during active cancer therapy (59).

Tai Chi or Qigong

Tai Chi and Qigong, a traditional Chinese mind-body practice, promote healing through slow movements, breath control, and meditation. Tai Chi serves as a therapeutic form of Qigong. These low-intensity exercises suggest to relief CRF by regulating immune and neuroendocrine function, balancing qi, and improving organ vitality, making them suitable for patients with limited physical stamina (53). Evidence is mixed but promising. While two early meta-analyses found no clear association between Qigong/Tai Chi and CRF relief, more recent reviews indicate potential benefits (5,52). Similar to the systematic review on Baduanjin Qigong (a traditional form of Qigong), a 2020 meta-analysis of 13 RCTs found that Qigong significantly outperformed conventional Western exercise in reducing CRF, particularly in patients with higher baseline fatigue (53,62). Based on five RCTs, the ASCO-SIO guidelines strongly recommend Tai Chi or Qigong practiced at low to moderate intensity for adults undergoing cancer treatment to manage fatigue. In older palliative care patients, such practices can also help maintain functional status and minimize personal care needs (63-65). However, no recommendations are made for post-treatment patients due to insufficient evidence (28).

Yoga

Yoga has earned widespread acclaim in managing CRF through integrating physical postures, breath control, and meditation. Several studies suggest it effectively reduces CRF during and after treatment, especially in breast cancer survivors, though findings are limited by methodological issues (5). A large RCT involving over 400 participants found significant improvements across all CRF subdomains with a 4-week standardized yoga program. Meta-analyses suggest a minimum of 150 minutes per week is necessary for noticeable benefits with CRF during chemotherapy or radiotherapy (52). Yoga appears more effective post-treatment, with supervised sessions showing greater efficacy than home-based practice. ESMO recommends yoga for cancer survivors based on multiple trials, including phase III studies and systematic reviews (16). NCCN also endorses it, while ASCO-SIO gives a conditional recommendation for post-treatment use, especially in women with breast cancer, citing insufficient evidence for patients in active treatment (28,52).

Massage

Through relaxation, circulation, and autonomic nervous system modulation to reduce stress and muscle tension, massage may help reduce CRF (21). Results from massage treatment in treating CRF have been conflicting. A 2020 Cochrane review and pooled analyses indicated no substantial benefit with massage (5,21). Massage during active treatment was shown to reduce CRF, according to a 2023 meta-analysis. Similarly, a 6-week Swedish massage routine significantly reduced fatigue compared to light touch or no treatment which was conducted on 66 post-treatment breast cancer survivors (5). Based on meta-analytic data, the NCCN guidelines advocate oncology massage during active treatment, despite conflicting evidence. The recommended frequency is 20–40 minutes twice weekly for 3–5 weeks (52). Furthermore, the ASCO-SIO guidelines currently find inadequate evidence to support massage as a standard CRF intervention (28).

Discussion

Key findings

CRF is an under-recognized clinical symptom that has a significant impact on the overall quality of life of cancer patients (7,66). Despite the growing prevalence in the last five years, it tends to be underreported and not treated adequately (67,68). To overcome this, there have been guidelines set for routine CRF screening, beginning at the first visit and repeated at every chemotherapy visit (69). Our review was an update on the advances in the field of CRF specifically from 2020 which showcased a rise in the recognition of this symptom in palliative care and general practice settings. The American Thoracic Society conducted a panel discussion on the topic of CRF from a multidisciplinary perspective to discuss its current scenario that highlighted the urgent need to prioritize CRF in patients affected with cancer (70).

Since 2020, there has been increasing evidence to reinforce the need for non-pharmacological interventions, including exercise, traditional Chinese medicine and psychosocial interventions which is a noteworthy progress (17). Zuo et al. [2023] conducted a literature review highlighting the benefits of mind body exercises in the form of yoga, and Tai Chi to alleviate CRF (17). The updated ASCO guidelines in 2024 guidelines recommend cognitive behavioral therapy and structured exercise as first-line interventions for CRF (28). Recent studies have highlighted an association between sleep disturbances and CRF. Improvement in sleep quality and CRF has been observed with interventions such as cognitive behavioral therapy for insomnia (CBT-I) and light enhanced CBT (71). Bean et al. reported the reduction in CRF among breast cancer patients receiving chemotherapy who received CBT-I (72). Bright white light has demonstrated reduced fatigue levels and improved quality of sleep, in patients receiving palliative care (73,74). Future research exploring effective strategies to implement these recommendations in busy palliative care clinics, such as developing multidisciplinary care pathways or digital CBT delivery models will be helpful in further understanding the effectiveness of these modalities in diverse patient-care settings.

From a screening and assessment perspective, there have been studies conducted since 2020 that have highlighted the use of various validated tools. Fisher et al. [2022] reported the use of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core (EORTC QoL) questionnaire and the FACIT-F tool (8,62,65,75,76). Additionally, the 10-point NRS, and Multidimensional Fatigue Symptom Inventory - Short Form (MFSI-SF) were already recognised as tools for assessing CRF (77). Poopady et al. [2023] conducted a systematic review on the measurement scales for CRF that reported the presence of 15 validated scales that require further exploration to be used as a general screening tool in all types of cancer patients (78). Gentile et al. [2022] recommended other tools such as BFI and MDASI for comprehensive assessment of CRF (7,10). Notably, a recent study highlighted that there is low content overlap between the various CRF scales and only a few scales like PFS, MFSI, and BFI cover the full symptom domain (79). In our current scoping review, we have tried to highlight the screening assessment tools that have emerged in the last 5 years.

Strengths and limitations

The main strength of this review is its focus on the recent updates and advancements in terms of diagnosis and management of CRF. Strong emphasis has been placed on multidisciplinary approaches and non-pharmacological interventions with an aim to reduce the reliance on pharmacological treatment options thereby, lowering the risk of medication based adverse effects. A potential limitation which is worth mentioning is the limited number of randomized controlled trials to support the incorporation of non-pharmacological interventions. In addition, with the presence of multiple screening tools, there is lack of uniformity and standardization across different types of cancers which makes it difficult to incorporate the same screening tool for CRF. Although there is a need of a standardized scale, there is a challenge in unifying it since CRF is influenced by individualized factors such as culture, language, and patient perceptions.

Comparison with similar research

The main highlights of this review are similar to the available literature that mention the decreased rates of recognition and treatment for CRF. Previous research also identified inadequate CRF screening and the general mindset of healthcare providers to dismiss or normalise CRF which resonates with our review. However, there is an extension to the previous findings with increased efforts to improve screening, and diagnosis. Poopady et al. [2023] described 15 validated scales for CRF measurement which is an extension from the existing knowledge tools such as EORTC QoL questionnaire, FACIT-F, and MFSI-SF. Subsequently, this work also highlights issues like training gaps and institutional barriers that are being increasingly discussed since 2020 (78). Previous studies focused on challenges like improper documentation and lack of algorithmic approach from the healthcare provider perspective, but our review also found the presence of survey-based studies done by Milzer et al. [2023] and Wagner et al. [2024] that demonstrate decreased awareness among physicians (80,81). Finally, this review also takes into account ethnic diversity and differences from a cultural standpoint which may impact management outcomes in minorities (82-85).

Explanation of findings

It is essential to address the system and healthcare provider related barriers that are associated with CRF which explain the current scenario of CRF in palliative care. Previously, improper fatigue documentation and insufficient palliative care referrals were barriers that were noted to hinder management. To tackle these barriers, the 2024 ASCO-SIO guidelines recommended strategies to make CRF management and assessment more accessible and consistent across various disciplines. Integrating fatigue screening tools in patient assessment and incorporating CRF management protocols in the electronic health records (EHR) were major recommendations. To promote interprofessional collaborative care, the guidelines also suggested the development of streamlined institutional pathways which include healthcare professionals from physical therapy, integrative medicine, clinical psychologists, nutrition experts, and social workers (80-86). This approach of shared responsibilities across disciplines is a great way to incorporate CRF management for every cancer. However, there are various barriers that hinder the implementation of these guidelines. Surveys conducted by Pearson et al. [2023] highlighted the patient related factors, including over prioritization of cancer treatment over fatigue management, lack of communication regarding fatigue, and reluctance to complain (87).

The main barriers identified in healthcare providers were failure of early recognition of CRF, inadequate training with respect to non-pharmacological interventions, and time limitations during outpatient clinic visits conducted by Milzer et al. [2023] and Wagner et al. [2024]; 72% of psycho-oncologists and 32% of the physicians were unaware about fatigue specific guidelines (80,81). This fact emphasizes the need to train physicians with a structured curriculum to recognize and address CRF in a timely manner. Interestingly, a study conducted in an Australian hospital found that 87% of the healthcare professionals who had adequate experience in oncology rated their expertise in CRF as limited or moderate. This indicates the insufficiency that exists in the initial training phase (87).

It is crucial to understand CRF in the context of end of life (EOL) situations in cancer patients as well. In such situations, the focus shifts towards managing acute symptoms such as pain, dyspnea, and gastrointestinal symptoms instead of fatigue. Some of the strategies that have been mentioned include integrating CRF assessment into EOL care protocols to ensure that there is enough focus on CRF. Interdisciplinary healthcare collaboration can also ensure that CRF is being addressed in the EOL situations. Another quintessential aspect that can keep the focus on CRF is to increase awareness amongst the patients and their families about CRF, emphasizing the need for open communication and shared decision making (88).

Implications and actions needed

While there have been many studies done in the last 5 years pertaining to the topic, there is still a need for more RCTs with a larger sample size to provide stronger evidence for the management of CRF (4,20). With the landscape of CRF management shifting towards non-pharmacological interventions, a common challenge would be to integrate it into the existing treatment algorithms. Subsequently, with more of such interventions being administered, monitoring must happen on a regular basis to understand the modifications needed to optimize CRF management. The non-pharmacological options have been integrated into an algorithm (as shown in Figure 4) that can act as a guide for palliative care specialists or other general physicians to address CRF.

Figure 4 An algorithm for the workup of cancer related fatigue in palliative care settings. ASCO, American Society of Clinical Oncology; CRF, cancer related fatigue.

Conclusions

CRF is being addressed in the recent years from multiple perspectives, including screening, diagnostic tools, and multimodal interventions. Despite the recent advances in the last five years, it is still underdiagnosed and undertreated. In palliative care settings, fatigue is a multifaceted symptom that affects the physical, mental and psychological well-being of a cancer patient. There has been considerable progress in management strategies and guidelines around the field of CRF, however it is essential to raise awareness, promote training, and support research in diverse palliative care settings to completely integrate CRF into routine cancer care. Work up algorithm must be integrated for CRF at every oncology visit rather than being limited to palliative care visits to ensure early and prompt detection.

Although pharmacological agents can provide significant relief, they must be balanced against the possible side effects and selected accordingly. There should be an integration of the pharmacological, non-pharmacological and complementary interventions into a comprehensive treatment pathway. Currently, there is variation in outcome measures, so there is a need for high quality studies to strengthen recommendations. To optimize benefit and minimize harm, individualized approach must be adopted considering patient’s symptoms, preferences, and comorbidities.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the PRISMA-ScR reporting checklist. Available at https://apm.amegroups.com/article/view/10.21037/apm-25-50/rc

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Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://apm.amegroups.com/article/view/10.21037/apm-25-50/coif). M.S. reports being employed by Klinik Barmelweid AG, a for-profit organization. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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