Experiencing and responding to chronic cancer‐related fatigue: A meta‐ethnography of qualitative research

Abstract Objective One of the most prevalent and disrupting symptoms experienced by cancer patients is chronic cancer‐related fatigue (CCRF). A better understanding of the chronic nature of CCRF can provide valuable insights for theory and practice. The purpose of this meta‐ethnography was to derive an overarching interpretative narrative on patients' experiences and responses to CCRF. Methods We conducted a comprehensive systematic literature search in five databases (05‐03‐2018). In addition, papers from reference lists were retrieved. Two researchers independently screened the papers for eligibility and appraised quality (CASP‐criteria). We followed the seven phases of meta‐ethnography to extract, translate, and synthesise first‐order constructs (ie, patients' views) and second‐order constructs (ie, authors' views) from the selected studies into third‐order constructs (ie, new interpretations). Results Of the 1178 collected articles, 16 articles were included. Through synthesis, a new figure of six interrelated third‐order constructs was developed: (1) embodied experience entails the dominating presence of the body; (2) (mis)recognition includes lack of recognition of CCRF by patients, relatives, and health providers; (3) small horizon describes a resultant narrowed world; (4) role change encompasses adopting other life roles; (5) loss of self refers to the impact on one's identity; and (6) regaining one's footing describes the struggle against CCRF, adaptation to CCRF and finally acceptance of a “new normal with CCRF.” Conclusion A new embodiment figure of CCRF with social (eg, (mis)recognition), spatial (eg, small horizon) and temporal dimensions (eg, regaining one's footing) was developed. This figure can help professionals to recognise CCRF, inform patients, and personalise treatment.


| BACKGROUND
Fatigue is one of the most prevalent and disrupting symptoms experienced by cancer patients. [1][2][3][4][5][6] The National Comprehensive Cancer Network (NCCN) has defined such 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". 7 In approximately 25% of patients, this fatigue is defined as chronic cancer-related fatigue (CCRF), because it persists for months to years after treatment completion. 6,8,9 CCRF is often accompanied by distress, interferes with daily activities and social relationships, and limits patient's quality of life. [10][11][12][13] In addition, CCRF is an important public health issue that incurs medical and societal costs. 14,15 The patient perspective and experiential knowledge of qualitative studies provide a richness and depth that complements quantitative studies. 16 As such, it can help to gain a better understanding of what CCRF entails and to provide insight into how to best treat these patients. 17,18 Several qualitative studies have examined patients' experiences with fatigue in different cancer populations. For example, Levkovich et al conducted interviews amongst breast cancer patients after chemotherapy and two main themes emerged: "Being imprisoned in the body of an 80-year-old" and "Family's bear-hug". 19 Scott et al (2009) analysed patients' quotations and published a systematic review of qualitative studies focusing on fatigue across the cancer trajectory. 20 They concluded that patients often describe how fatigue affects their lives, rather than the sensations of fatigue. 20 Moreover, "tiredness" does not capture the multidimensional character of the patient's fatigue experience. 20 So far, most qualitative reviews 20,21 have focused on experiences of fatigue in the acute phase of treatment, whilst the long-term chronic nature of this condition has remained less well understood. Therefore, a more detailed and up-todate description of the chronicity of post-treatment fatigue is required.
Although previous qualitative research on CCRF provided valuable insights, the increasing number of new studies made it difficult for researchers and clinicians to appreciate which insights were most useful for further research or clinical practice. Thus far, qualitative reviews have performed comparative and aggregative analyses. 20,21 In order to personalise treatment for CCRF, a more interpretative approach to analyse individual studies is needed. Therefore, we conducted a meta-ethnography to create an overarching interpretative narrative, whilst maintaining the integrity of the individual studies. [22][23][24][25] This meta-ethnography focused on how patients experience and respond to CCRF.

| Design
This study was based on Noblit and Hare's interpretative and iterative approach for conducting a meta-ethnography, modified with knowledge from practical examples in health care whilst utilising the eMERGe guidance for reporting. [24][25][26][27][28] The seven phases used in this approach were followed: (a) formulating the research question;

| Quality appraisal
The selected papers were reviewed individually by T.B. and M.S. using the 10-item Critical Appraisal Skills Programme (CASP) checklist to assess whether the results were valid and reliable. 29 Whilst the use of quality criteria is widely debated, we chose this commonly used appraisal tool to gain insight into the content and quality of the current evidence. The intention was not to reach consensus in scores on the CASP questions. The answer to each CASP question was counted by each researcher as fully addressed (three points), partially addressed (two points), and not addressed (one point), leading to a score ranging from 10 to 30.

| Data-analysis and synthesis
After reading and re-reading the included papers, first-order (ie, patients' views on experiences) and second-order constructs (ie, authors' interpretations of patients' views on experiences) of the selected studies were identified and listed with the help of the software programme, MaxQDA 2018 (release 18.1.1). First-order constructs involve patients' understandings (quotes) of CCRF and were extracted from the results section of the selected paper. 23,24 Second-order constructs involve the authors' interpretations (themes and concepts) of patients' understanding of CCRF and were usually extracted from the discussion and conclusion sections of the selected paper. 23,24 We created third-order constructs (ie, new interpretations) by translating and synthesising these first-order and second-order constructs.
Different constructs between and within studies were compared.
As the content showed primarily similarities, a reciprocal translation was applied. Inconsistencies were handled by refutational translation.
For example, the third-order construct (mis)recognition encompassed both misrecognition and recognition. Thematic analysis started by listing constructs in conceptual categories of the most recently published and conceptually rich paper. 19 T.B. and R.W. independently listed the first-order and second-order constructs of four different papers. 19,[30][31][32] Subsequently, the construct list of these papers was compare to reach consensus, creating a final list with which the other papers were Group discussions were based on merging conceptual categories (subthemes). Patients' experiences and responses to CCRF were approached as a whole, and descriptions of temporal changes in these experiences and responses were taken into account. During the last group discussion, we adopted a line of argument synthesis and visualised the relations between third-order constructs (meta-themes) to complete the overarching narrative. 23,24 We cross-checked to determine whether the individual studies fitted these meta-themes.

| Meta-themes
The first-order (quotes in italics) and second-order (themes/concepts in normal font) constructs were translated in six new meta-themes: embodied experience, (mis)recognition, small horizon, role change, loss of self, and regaining one's footing (Table S4). Individuals differed in their experiences and responses. That is, not all individuals had all experiences/ responses described in the meta-themes.

Embodied experience
Patients' descriptions of CCRF were embodied, meaning that their experiences were predominated by bodily sensations or bodily symptoms, [38][39][40]44,45 such as "heavy limbs", 39 "legs like jelly or wobbly legs", 39 "feeling weak", 19,31,45,46 or "paralysis". 42 CCRF was often described as a whole body experience: "the body is worn-out", 39,40,46 "physically exhausted", 19,39,45 "body doesn't want to go on", 30 or "body cannot heal, nor can it function well". 46 One patient commented that her body could not carry her: "It's like the body can't … carry you. It's a real weakness … a bad feeling. And it's simply … like you don't have any energy, no energy for anything.
Nothing, like you're … you're like a zombie; you just sit there … like a couch potato" F (Female), 67 (age), breast cancer (cancer type) 19 Whilst several studies reported cognitive and affective symptoms of CCRF, 19,[30][31][32][38][39][40]43,[45][46][47] patients often described these symptoms as part of the body. For example, the metaphor "the brain is out of function" was commonly used to describe a cognitive sensation of tiredness in the head. 30,40,41 Consequently, patients reported they became more aware of their bodies in various ways: "the fatigue takes over every aspect of the body" 19 ; "the feeling that the body dominated the mind" 39 ; or "the whole body is shattered". 40 Other patients described CCRF as "the betrayal of the body" and "trapped in an old, sick body". 19,39,41 Patients' experiences revealed that physical and mental symptoms of CCRF are strongly interrelated. 37,39,40,[45][46][47] One patient described this relationship: "Fatigue is a physical experience but there is also something psychological; if one thinks of being a death candidate, it's not cheering you up" N/ A (Identification Not Available) 40 (p87).

(Mis)Recognition
As CCRF is invisible, and healthy individuals also experience tiredness, patients felt it was difficult to explain to others how intense CCRF is. 30 "Because I look so much better than when I was having treatment, people think that I am back to prior fitness" F, N/ A 44 (p153).
Patients also experienced being misunderstood by their friends and family. 30,43,44,46,47 One patient described how the family failed to remember the fatigue: "My family is pretty good but they can easily forget how tired I can get as this is not obvious" F, N/ A 44 (p153).
Patients often experienced a conflict between their own needs and the expectations around them. 19,47 Patients felt pressured to cease being sick and move on 44 and, as a result, did not feel supported by their family and friends. 19,42,43,47 One patient reported about her unsupportive mother: "My mum basically accused me of not trying hard enough to get over it" F, N/ A 44 (p156).
Moreover, in some papers, patients indicated that health care professionals did not recognise CCRF. 42,44 Because of a lack of objective medical parameters, health care professionals approached CCRF as a problem with "no symptoms, no cause and no cure". 44 Therefore patients had negative experiences in communicating about CCRF with health care professionals and sometimes had the feeling they were not being heard or taken seriously. 44,45 This was primarily caused by a lack of awareness amongst health care professionals. 32,44 Patients voiced that for health care professionals CCRF is "the least worrying side effect" of cancer treatment, and as a result, "comes at the bottom of the list". 32 This resulted in the management of CCRF being a low priority. 32 Patients often did not get the right information about what they could expect in terms of CCRF after treatment. 32,44,46 Patients who were informed ahead of time appreciated the information that fatigue was a common experience and were then able to legitimise their fatigue. 32,43 One patient explained how better information improved recognition of CCRF: "This material has helped a lot, it has given me good advice and especially I felt reassured that fatigue was not absurd or unusual but that others suffer from it as well" N/ A 32 (p105).
Patients were reluctant to talk about their fatigue in general which contributed to the "misrecognition" of fatigue. 43 As a result of not being informed and prepared by health care professionals for experiencing CCRF after cancer treatment, patients had pessimistic beliefs, for example CCRF is: "untreatable", 45 "inevitable", 43,45,47 "sign of decline in health", 30 "it is a sign of not being successfully recovered from cancer or cancer recurrence", 47 "it indicates the body cannot heal nor function well", 46 "it elicits concerns about survival", 31 or "caused by the unknown". 31 Patients felt embarrassed, which further limited their willingness to discuss CCRF with others. 19,39,43 Patients experienced a gap between expected "life after illness" and reality. 19 Furthermore, patients could lose control of their own story, due to the lack of conceptualisation of the CCRF they felt in a "limbo between sickness and survivorship". 44 One patient expected the future to be limited by their fatigue: "I've settled in my mind that I'm going to get worse; I expect it to happen gradually, and I expect one of the ways it will show is that I will be more tired than I am now" N/ A 37 (p114).
On the other hand, in some studies, patients recognised fatigue as "abnormal" and "pathological" when it persisted after treatment 39,41,42 and sought medical help. 19,[30][31][32][43][44][45][46]48 For some patients, CCRF had become "an illness with its own rights". 39,42 Patients with optimistic beliefs expected a future of normal prediagnosis levels of fatigue 37 or convinced themselves to be okay. 32 One patient reported: "I don't think there's going to be any problem in the future" N/ A 37 (p114).

Small horizon
The physical, emotional, cognitive, and social consequences and limitations of CCRF resulted in a "small horizon" for some patients. It reduced their freedom and narrowed their scope of abilities. Patients were unable to regain their precancer activity level. 31 These dysfunctions and inabilities were often accompanied by feelings of isolation or nonbelonging. 31,39,44 Patients used the following metaphors to describe their nonbelonging: "gradual submersion", "drowning", and "rising water". 39 Some patients wanted to be left alone and face their fatigue by themselves. 19,43,44 Because of the struggle with dysfunctions and inabilities, the experience of CCRF had a major impact on patients' motivation to do things. 30,38,39,41 This loss of interest in enjoyable things and in life in general 30,38,39,46 contributed to the perception of "small horizon." One woman described this as a state of lethargy: Suffering from CCRF and becoming dependent also affected the partner role. 19,31 In this example, the partner was supportive, and the patient was accepting help: "I actually felt like I was being led like a little girl … whose father is leading her [by the hand]" F, 43, breast cancer 19 (p7).
Partners could also be less supportive or even unsupportive.
Patients indicated they experienced no closeness in their relationships, or even failure of marriage. 19 People with CCRF chose to cut back on their workload, to quit work or to retire from their work to have more time for themselves. 30,31,37,42,47 One patient described that suffering from CCRF prevented him from returning to work: "I was determined to go back to work as soon as I possibly could. I mean I haven't a particularly hard job, but then I did it for a week and just had to, just couldn't do it anymore, and it really shocked me, that I felt so tired, so fatigued…so I think it would probably be quite handy to just make people aware of the fact that even though you are feeling quite well that the fatigue is going to get you, possibly will get you, and may well mean that you can't work" F, N/ A 32 (p106).

Loss of self
People described their change as that from being a healthy person to being a patient with cancer, suffering a different and persistent fatigue compared with the fatigue they experienced precancer. 30 Patients described different feelings related to "loss of self", for example a lack of control, 19 30,40 and uncertainty about the ability to cope with fatigue. 19,30,31,[38][39][40] Patients also experienced a loss of purpose in life, for example, by losing their career plans. 31,44 In some cases, patients expressed an awareness of the finite nature of life: "Hanging on to life by a thread of cotton", "walking along the razor's edge" or "along a tight rope" N/ A 39 (p304).
As a result of these feelings, including their small horizon and dependency, patients described a loss of self. 39 Patients grieved for the person they had been and realised they could not go back to their "old self" before the cancer. [37][38][39]44 One patient quoted: "I'm obviously not the man I was" N/ A 37 (p114).
Other patients commented on their changes in identity, for example from an active to an inactive person. 30 accepting what you can't" N/ A 37 (p114).
As part of finding a "new normal" patients explored and reframed meaning by naming or assigning a cause to CCRF to give it a place in their life. 30,31,39,44 Some patients were informed by their health care professionals to set goals and visualise strategies to overcome CCRF, to legitimise fatigue and get support from their family members. 32,[42][43][44]46,48 One patient described the advantage of legitimisation of fatigue: "It is a matter of legitimisation to experience fatigue as a usual experience" N/ A 32 (p105).

| Relations of meta-themes
The six meta-themes we identified are interrelated. Central to all themes is the phenomenon of embodiment. Acknowledging that humans are primarily embodied beings-instead of composites of (disembodied) mind and body-embodiment refers to the fact that action, perception, orientation, and cognition are based on our being embedded in a certain time and place, and social situation through our bodies. Figure 1 captures the embodied dimension of CCRF. Previously, the onset of fatigue by patients undergoing treatment has been linked to paying explicit attention to the body as problematic and as an object. 50,51 In accordance with these studies, our results show that the awareness of the body in a negative way dominates patients' experience and is described as "old" and "sick." Although the human experience is always embodied, in everyday life the body is seldom a thematic object of experience, as there are less thoughts about the body and it dis-appears from attention. 52,53 Drawing on Leder's analysis of how one's own body can be either present or absent to oneself, the term dys-appearance (dys is a Greek prefix) is used to describe the situation when the body appears to the patient as "ill" or "bad". 52,53 Because the body dys-appears whilst being chronically fatigued, it becomes the focal point of attention. The body loses its taken-forgranted dimension. 52 Consequently, the agency over one's body declines. 52 From a phenomenological point of view, it is claimed that whenever one's body appears obstinately in the foreground, one's possibilities to act and to endow meaning to one's situation, also defined as "I can," shrink. 54 As a consequence of these reduced possibilities, the ability to adequately respond to the situation lessens. 54 Regaining one's footing, by contrast, implies that one is able to resume

| Study limitations
A potential limitation of this meta-ethnography is the inclusion of mixed cancer patients' samples: on-/post-treatment, [30][31][32][37][38][39][40]43,45,48 and curative/ advanced stages of disease. 30,31,[38][39][40]42,45,48 Only in the case where the authors reported patients' experiences during  Although some studies may have been of a bit lower quality, the content of all studies was valuable and informative to broaden the perspective on CCRF.
The starting point of the analysis was the newest and conceptually richest paper of Levkovich et al. 19 We could not initially discern whether or not this starting point affected the interpretation of concepts of other studies. However, as we conducted inductive analysis and cross-checked all studies afterwards, we expect the impact to be minimal.
Quality assessment revealed that one of the most frequent shortcomings was the lack of description of the relationship between researchers and participants. 31,32,37,[39][40][41][42][43][44][45][46][47] Transparency in terms of the role of researchers and the ongoing critical reflection of their own biases is important in qualitative research, because of the level of subjectivity in this methodology. Future qualitative research should be attentive to the description of their methods section and should use, for example, the COREQ checklist. 58 The quality of the included studies impacts on the quality of the present results. However, by having carefully applied the meta-ethnography method, our results are considered to be reliable.

| Clinical implications
The social, spatial, and temporal dimensions underline CCRF's complex manifestation, which, ideally, requires a person-centred approach by health care professionals. 59 During, as well as after, treatment, patients need information on CCRF and other side effects. 44 By normalising patients' experiences, they can regain a sense of control.
The figure could also help advise patients on helpful strategies to manage CCRF. For example, by first explaining embodiment to the patient, therapy could focus on softening bodily dys-appearance and, as such, enable bodily dis-appearance. 63

| CONCLUSIONS
In conclusion, the main finding of this meta-ethnography is that patients' experiences and responses to CCRF are based on being embodied. Our findings emphasise the importance of informing patients to improve recognition and healthy responding to CCRF. In future qualitative studies, lived embodied experiences and helpful patterns of responding to CCRF could be further investigated in more heterogeneous samples, including more males and patients with different cancer types. To tailor treatment to the individual, insight into calculating the interrelationship between symptoms and ways of responding to CCRF is needed. 64