Fatigue Experience in Oncology; a Targeted Qualitative Literature Review and Novel Patient-Centric Conceptual Model.

Key Summary Points

Fatigue is described variably in terms of severity, frequency, duration and onset across different types of cancers, treatment stages and international settings Both physical and mental fatigue were reported by patients indicating the all-encompassing effect of fatigue Weakness and low stamina (physiological), needing to rest/recover (physical) and apathy (emotional) were all frequently reported impacts of cancer-related fatigue Fatigue also impacted areas of patient’s lives such as their activities of daily living, sleep, social functioning, relationships and work, demonstrating the multifaceted nature of fatigue Fatigue significantly affects patients living with cancer and it is therefore important to understand how it should be measured in oncology clinical trials These findings may also facilitate clinician and patient conversations around cancer-related fatigue and how it may be best treated or addressed

Introduction

Fatigue is one of the most common symptoms experienced by patients with cancer, with an overall prevalence of 49% [ 1 ], and is also associated with several cancer treatments [ 2 ] in addition to the diagnosed disease. Cancer-related fatigue is defined 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 that interferes with usual functioning [ 3 , 4 ]. Moreover, cancer-related fatigue is less likely to be relieved by rest than fatigue experienced by healthy individuals [ 3 , 4 ]. Fatigue at cancer diagnosis [ 5 , 6 ] and during survivorship [ 7 ] is associated with increased mortality. Although guidelines recommend screening for and continued management of cancer-related fatigue from diagnosis through to follow-up [ 4 ], fatigue is under-diagnosed and under-treated [ 3 , 4 , 8 ]. Studies report that approximately 60% of patients, 2 years after diagnosis, did not feel well informed about fatigue. Approximately 40% had never been asked about being exhausted by their treating physician [ 9 ], while up to 50% of survivors describe unmet needs in relation to discussing cancer-related fatigue, receiving advice or receiving help [ 10 – 12 ].

Fatigue is typically considered to be best measured through patient-reported outcome (PRO) measures, as it is a symptom that only patients can feel and report on. However, a complexity in measuring fatigue is that it is often experienced alongside and moderated by other cancer-related symptoms, including pain, sleep disturbance and depression. For example, there may be a relationship between fatigue and depression [ 13 ] and fatigue and physical function [ 14 ]. Conceptualising the patient experience, typically through the development of a conceptual model, is a key initial step in identifying PROs to measure fatigue. While indication-specific conceptual models of fatigue provide a focused understanding of the experience of fatigue in particular oncology indications, they do not holistically represent fatigue across oncology indications, throughout the course of the disease, and evaluate how cancer-related fatigue can be associated with health-related quality of life (HRQoL) and functional impacts [ 15 , 16 ].

The primary aim of this targeted qualitative literature review was to characterise the patient experience of cancer-related fatigue by identifying how patients describe fatigue in the context of oncology, including emotional, cognitive and physical fatigue, whether fatigue varies according to the treatment stage, and the impact of cancer-related fatigue on how patients feel and function.

Methodology

Eligibility Criteria

Studies with a qualitative methodology that described the patient experience of cancer-related fatigue, across all oncology indications, between 2018 and August 2023, were eligible for inclusion. Full details of the eligibility criteria are given in Table 1 . Table 1 Eligibility criteria Criteria Include Exclude • Population Adults diagnosed with any type of cancer Studies which enrolled paediatric participants only Studies with mixed populations were eligible if data were reported separately for adults and paediatrics • Intervention/comparator No restrictions No restrictions • Study design Studies with qualitative methodology (e.g. qualitative interviews or focus groups) Studies with quantitative methodology only Case reports Review papers were not eligible for inclusion, but highly relevant review papers (i.e. those summarising qualitative research) were reviewed to determine whether any of the reviewed primary studies were eligible for inclusion via hand-searching methods • Outcomes Patient experience of cancer-associated fatigue Patient descriptions of patient’s fatigue and associated HRQoL impacts of cancer fatigue Outcomes which were reported as direct quotes or author summaries of collected data Patient experience of other symptoms and impacts of cancer or cancer treatments (i.e. not fatigue) Quantitative results only (e.g. COA measure scores) Studies using multiple-choice survey methodology were flagged for discussion and highly relevant papers were included if there was a lack of fully qualitative research • Publication language English Non-English publications with English titles and abstracts Non-English publications with non-English titles/abstracts • Date of publication 1 January 2018 to 21 August 2023 Published before 1 January 2018 COA clinical outcomes assessment, HRQoL health-related quality of life

Data Sources, Search Strategy and Quality Assessment

Relevant articles (full publications or conference abstracts) indexed on MEDLINE ® , Embase and PsycINFO were identified using database search strings. Three search strings were developed to account for differences in syntax within each database and combined terms for “cancer” AND “fatigue” AND “qualitative research studies” OR “conceptual models”. Supplementary hand-searching of the Food and Drug Administration (FDA) and European Medicines Agency (EMA) websites, and the reference lists of any included studies identified from database searches, was conducted.

Electronic database searching was conducted on 21 August 2023. A bespoke Microsoft Access database, with all identified records uploaded, was used to manage citation screening. Once duplicates had been identified and removed, studies were initially screened by their titles and abstracts (first pass) by two authors. Potentially relevant studies were obtained in full and reviewed (second pass) by two authors. Any discrepancies in decisions were resolved through discussion with the wider team of authors. The reasons for exclusions at first and second pass (in accordance with the eligibility criteria presented in Table 1 ) were summarised in a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flowchart (Fig. 1 ). The Critical Appraisal Skills Programme (CASP) checklist for qualitative studies used to assess the quality of included studies is available in Table S1 [ 17 ]. Fig. 1 PRISMA diagram. PRISMA Preferred Reporting Items for Systematic Reviews and Meta-Analyses

Data Extraction and Analysis

Data extraction and analysis of patient quotes or author descriptions/interpretations was conducted by two authors trained in qualitative research techniques. Extracted data underwent secondary analysis using semantic, qualitative, directed content analysis techniques [ 18 , 19 ]. The analysis followed an experiential, realist approach, which focused on participants’ individual perspectives and experiences.

Qualitative directed content analysis, consisting of a five-step process, was applied to all included data [ 20 ]: immersion in the data, coding, iterative review of codes, defining and refining concepts and domains and reporting. Coding of extracted data was facilitated by the qualitative analysis software, ATLAS.ti version 9. Extracted data were then synthesised to develop a conceptual model to visually depict the patient experience of cancer-related fatigue.

Ethics Compliance

This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.

Findings

Study Selection

The electronic search yielded 1210 articles. Duplicates were removed ( n = 368), and records were screened by title and abstract (first pass, n = 842). Records were removed if they did not meet the eligibility criteria ( n = 679). The full-text publications of the remaining records were reviewed (second pass, n = 163), resulting in 142 publications which appeared eligible for data extraction ( n = 40 excluded, n = 19 identified via supplementary hand-searching from FDA/EMA webpages and references from included studies).

A study selection meeting was held with all authors to select the most relevant publications for development of the conceptual model. Publications were initially ordered on the volume of extractable qualitative data (e.g. pages, paragraphs or sentences of direct quotes or author interpretations). To avoid the selection, and subsequent overrepresentation, of specific cancer indications that have been researched more intensively than others, consideration was given to a range of cancer types across oncology (e.g. solid tumours, blood cancers, etc.) and varied representation of cancer journey stages. Any qualitative publications containing a conceptual model of fatigue in oncology were also recommended for inclusion. The 26 most relevant publications were retained for data extraction (Fig. 1 ).

Study Characteristics

In total, 26 publications reporting on the experiences of 512 patients with cancer-related fatigue across 28 different oncology indications were included in this review. A wide range of oncology indications were identified, most frequently breast cancer [ 21 – 25 ], lung cancer [ 22 , 26 – 29 ] and skin cancer [ 15 , 16 , 30 , 31 ], with five studies including a mixed population of cancer indications [ 21 , 22 , 27 , 32 , 33 ] (Fig. 2 ). Across the included studies, sample size (range: 7–37 patients) and mean patient age (mean range: 53–76 years) varied; 51% of patients were female ( n = 261/512) and 49% were male ( n = 251/512). Most studies were conducted in the USA [ 16 , 28 , 31 , 33 – 39 ] or Europe [ 21 , 23 , 27 , 40 ] and utilised semi-structured interviews ( n = 22) as a method of data collection. A variety of analytic approaches were used, most often thematic analysis ( n = 11) [ 15 , 22 , 24 , 27 , 31 – 33 , 36 , 39 , 41 , 42 ] and content analysis ( n = 10) [ 16 , 23 , 25 , 26 , 29 , 32 , 35 , 37 , 38 , 40 ]. A summary of the characteristics of the included studies is provided in Table 2 . Fig. 2 Summary of study oncology indications Table 2 Characteristics of the included studies ( N = 26) Study Sample size, N Cancer type(s) Female patients, n Age, years (mean [range]) Country Arizona, 2020 [ 22 ] 15 Mixed population (nasopharyngeal, n = 3; abdominal, n = 2; thyroid, n = 2; rectal, n = 1; nasal/sinus, n = 1; brain tumour, n = 1; breast, n = 1; lung, n = 1; osteosarcoma, n = 1; oral squamous cell carcinoma, n = 1; colorectal, n = 1) 0 49 [19–69] Indonesia Barrett, 2023 [ 15 ] 28 Soft tissue sarcoma 22 43 [22–79] Not reported Bootsma, 2023 [ 21 ] 25 Mixed populations (breast, n = 10; haematological, n = 8; digestive system, n = 5; head or neck, n = 2; male genitalia, n = 2; urinary tract, n = 2; bone or soft tissue, n = 1; brain and central nervous system, n = 1; skin, n = 1; gynaecological, n = 1) 16 53 [21–80] The Netherlands Bradford, 2023 [ 41 ] 23 Myeloproliferative neoplasms a (polycythaemia vera, n = 13; essential thrombocythaemia, n = 8; myelofibrosis, n = 5; ‘other’, n = 1) 18 Not reported [32–76] Australia Cancer Support Community, 2021 [ 34 ] Not reported Not reported Not reported Not reported US Charles, 2021 [ 23 ] 15 Breast cancer 15 60 [45–81] France Cheung, 2019 [ 43 ] 29 Melanoma 18 52 [28–69] Canada Dolgoy, 2020 [ 32 ] 25 Mixed population (oropharynx, n = 20; larynx, n = 3; thyroid, n = 2) 10 62 [47–73] Canada Dong, 2021 [ 29 ] 16 Lung cancer (small cell, n = 4; non-small cell, n = 12) 4 66 [38–80] China Eek, 2021 [ 35 ] 40 Chronic lymphocytic leukaemia 19 18–35 years: 2 36–50 years: 8 51–65 years: 20 > 66 years: 10 b US Gable, 2018 [ 36 ] 7 Hepatocellular carcinoma 3 45 [33–64] US Gries, 2021 [ 16 ] 30 Multiple myeloma 16 69 [55–88] US Guillemin, 2022 [ 33 ] 25 Mixed population (colon, n = 9; rectal, n = 3; colorectal, n = 13) 17 52 [26–72] US Homkes, 2023 [ 28 ] 7 Lung cancer 5 > 40 c US Iguchi, 2022 [ 44 ] 8 Prostate cancer 0 Not reported [58–76] Japan Kim, 2020 [ 24 ] 16 Breast cancer 16 48 [25–65] Korea Konidaris, 2023 [ 31 ] 15 Basal cell carcinoma 9 57 [38–73] US Levkovich, 2019 [ 25 ] 13 Breast cancer 13 52 [34–67] Israel Li, 2023 [ 26 ] 21 Lung cancer 6 58 [37–81] China Mikkelson, 2019 [ 27 ] 23 Mixed population (lung, n = 11; pancreatic, n = 7; biliary tract, n = 5) 11 Not reported [65–85] Denmark Milne, 2020 [ 30 ] 23 Melanoma 5 59 [32–86] Australia Parthipan, 2023 [ 42 ] 36 Prostate cancer 0 76 [not reported] Canada Poort, 2018 [ 37 ] 10 Chronic myeloid leukaemia 4 53 [37–70] US Stuhlfauth, 2018 [ 40 ] 9 Colon cancer 5 58 [50–73] Norway Tang, 2018 [ 38 ] 37 Pancreatic cancer 21 66 [44–92] US Trudeau, 2020 [ 39 ] 16 Myelodysplastic syndrome 8 Not reported [51–91] US US United States a Counts are not mutually exclusive b Data came directly from the papers selected, with no additional data analyses. Mean age was not provided, ages were presented as categories c Data came directly from the papers selected, with no additional data analyses. Mean age was not provided, but eligibility criteria specified that patients be 40 years of age

The number of studies mentioning each concept evaluated (fatigue triggers, fatigue descriptors, fatigue impacts, coping strategies and unmet needs) and supportive quotes are presented in supplementary tables (Table S2–S16).

Fatigue Triggers

The most commonly reported trigger for cancer-related fatigue was treatment (or the absence of certain treatment, e.g. blood transfusions), including venesections, immunotherapy and novel hormone therapy [ 15 , 22 , 25 – 28 , 32 – 34 , 37 – 44 ]. Cancer itself was explicitly acknowledged as triggering fatigue [ 15 , 22 , 26 , 32 , 33 ], along with certain cancer symptoms or side effects of treatment, such as pain [ 41 ], dyspnea [ 27 ], diarrhoea, acid reflux, dry mouth and infections [ 38 ].

Studies reported that older age [ 25 , 26 , 38 , 41 , 44 ] and increased distress [ 22 , 29 , 41 ] or uncertainty [ 22 ] could contribute to cancer-related fatigue. Fatigue was also attributed to exertion/activity [ 24 , 25 , 32 , 39 , 41 ], travel/commuting [ 41 ] and the level of rest patients received, with a lack of rest/sleep [ 22 , 44 ], too much rest [ 28 ] or altered body clock [ 41 ] triggering fatigue. Patient diet [ 29 , 41 ], appetite [ 22 , 27 , 29 ] and blood parameters [ 41 ] further impacted fatigue, as did ambient temperature (Table S2) [ 41 ].

Fatigue Descriptors

As the studies included in this review represented diverse experiences, fatigue descriptors were stratified into temporal stages according to whether the fatigue was experienced while living with cancer or during active treatment, post-treatment or long-term in cancer survivors (up to 2 years after completion of primary treatment). General descriptions of fatigue, such as low/lack/loss of energy, tiredness and exhaustion, were reported across all three temporal stages related to treatment. Cognitive or mental fatigue was described by patients living with cancer or during active treatment who had haematological malignancies [ 35 , 41 ]; fatigue led to brain fog and difficulty with focus, concentration or paying attention [ 26 , 35 , 41 ] finding words and memory [ 41 ], leaving patients prone to errors or feeling spacey and jetlagged [ 41 ]. Severe fatigue experiences, such as overwhelming or crippling/crushing fatigue, were most frequently reported in patients living with cancer or during active treatment and post-treatment, with long-term fatigue in cancer survivors described as invisible to others (Table S3).

The onset of fatigue was reported as unpredictable and/or unexpected across all temporal treatment stages [ 25 , 27 , 32 , 34 ], and was described as “sudden” [ 25 , 41 ]. However, in patients who were living with cancer or receiving treatment for their cancer, fatigue would begin after periods of rest or sleep [ 16 , 36 , 41 , 44 ] (Table S4).

The frequency and duration of cancer-related fatigue episodes varied across temporal stages. Some patients living with cancer or receiving treatment [ 22 , 31 , 33 , 39 , 41 , 43 ] and post-treatment [ 25 ] reported that fatigue occurred persistently across each day, while other patients who were living with cancer or receiving treatment reported that fatigue fluctuated [ 27 , 28 , 37 , 38 , 41 , 44 ]. Similarly, fatigue episodes were also described as intermittent, or as occurring in waves, by patients who were post-treatment [ 25 ] and survivors [ 32 ] (Table S5).

Fatigue was often described as chronic by patients who were living with cancer [ 33 , 41 – 43 ] and survivors [ 21 , 40 ]. However, other publications reporting on patients living with cancer or receiving treatment, or post-treatment, described more acute durations of fatigue, limited to days [ 25 , 38 , 42 ], weeks [ 26 , 38 ], hours [ 25 , 41 ] or months [ 41 ] (Table S6).

Fatigue was commonly described as either severe or highly bothersome [ 21 , 24 , 25 , 33 , 34 , 39 , 41 – 43 ], debilitating [ 34 , 43 ], extreme [ 21 , 25 ] or uncontrollable [ 25 , 26 , 32 ]. Publications reported that fatigue was not relieved with rest [ 22 , 25 , 28 ] or treatment [ 22 , 25 , 40 ] and worsened/built during the day [ 21 , 26 , 29 , 41 , 44 ] or varied in severity [ 16 , 21 , 25 , 31 , 32 ]. However, a number of papers reported that fatigue was tolerable [ 28 , 29 , 31 , 38 , 39 , 43 , 44 ] or eventually improved following treatment or for other unspecified reasons [ 25 , 27 , 38 ] (Table S7).

Impacts

Physiological

The most frequently reported physiological consequence of cancer-related fatigue was physical weakness, including when standing and carrying items [ 16 , 21 , 22 , 25 , 26 , 31 , 33 – 35 , 38 – 42 ], and low stamina in relation to physical activities [ 16 , 30 , 39 – 42 , 44 ]. Patients experienced shortness of breath (dyspnoea) [ 21 , 26 , 27 , 34 ], lethargy [ 30 , 39 ], pain [ 23 ], dizziness and clumsiness due to their fatigue [ 41 ], along with a reduction in, or absence of, appetite [ 26 , 27 , 29 , 44 ] (Table S8).

Physical

The most frequently reported physical impact of cancer-related fatigue was a need to rest and/or sleep both post-exertion and to recover after completing activities [ 16 , 21 , 24 – 29 , 32 – 36 , 38 , 39 , 41 – 44 ]. Getting out of the house was challenging because of fatigue, with some patients reporting that it was easier to stay at home [ 24 , 29 , 30 , 36 , 39 , 41 , 44 ].

Patients reported limited movement or an inability to move at all [ 16 , 25 , 26 , 32 , 35 , 39 , 41 , 43 , 44 ] and described difficulty with transitional movements [ 22 , 24 , 25 , 33 ], climbing stairs [ 21 , 33 , 36 , 39 ], standing, even briefly [ 25 , 31 , 33 ] and getting out of bed, with some patients essentially bedbound [ 30 , 37 – 39 ]. Patients also experienced psychomotor slowing [ 26 , 38 , 42 ]. For some patients, fatigue was so severe that they were unable to talk [ 25 , 26 ].

Cancer-related fatigue also impacted patients’ ability to engage in physical activity, including unspecified exercise [ 24 , 26 , 32 , 34 , 35 , 38 , 41 , 42 ], any form of physical activity (described more generally) [ 16 , 27 , 28 , 33 , 35 , 37 ], light/moderate activity [ 30 , 39 ], sport/vigorous activity [ 22 , 26 , 33 , 39 , 41 ], walking [ 16 , 21 , 26 , 33 , 34 , 39 , 42 , 44 ] and cycling [ 33 , 34 , 39 ] (Table S9).

Emotional

Cancer-related fatigue frequently led to apathy, with patients describing a lack of motivation and an inability to enjoy activities that they had previously liked [ 16 , 21 , 26 – 30 , 32 , 34 , 35 , 41 , 44 ]. Sadness/depression [ 24 – 26 , 29 , 30 , 32 , 34 , 36 , 41 , 44 ], distress [ 22 , 25 , 26 , 29 , 32 , 38 , 41 ] and hopelessness [ 26 , 37 , 41 ] were also reported. Fatigue led to a loss of self/autonomy for some patients, who described grieving for their previous self, acknowledging that they had changed because of their fatigue experiences [ 21 , 22 , 25 , 34 , 40 , 41 ]. Patients reported that they felt they were a burden to others [ 22 , 25 , 26 ], helplessness [ 22 , 25 , 26 , 30 ], loneliness [ 24 , 25 ] and, less frequently, feelings of confusion [ 41 ], shock, disappointment or suffocation [ 25 ].

Patients also experienced anxiety/worry due to the unpredictability of their fatigue, anticipating bouts of fatigue and doubting that their treatment regime was efficacious because of their fatigue experiences [ 21 , 26 , 29 , 32 , 41 ]. Patients frequently reported uncertainty/self-doubt regarding the authenticity of their fatigue experiences and their ability to cope [ 23 , 25 , 29 , 30 , 41 ], and feared death, the potential loss of their independence and leaving the house/meeting other people [ 25 , 26 , 29 ], although some expressed determination to overcome fatigue [ 22 , 25 , 29 ]. Anger/frustration was common [ 16 , 22 , 25 , 26 , 32 , 35 , 41 ], and patients often felt more irritable regarding their own actions (such as accidentally knocking things over) and, at times, with the continued presence of others [ 22 , 25 , 35 , 37 , 41 ] (Table S10).

Activities of Daily Living

The most frequently reported effect of fatigue on activities of daily living was difficulty completing household tasks [ 16 , 21 , 26 , 27 , 31 – 33 , 35 , 36 , 39 , 41 , 44 ], eating or cooking [ 21 , 25 , 26 , 31 – 34 , 39 ], gardening [ 30 , 41 , 44 ] and shopping/running errands [ 39 ]. Patients also struggled to engage in a range of leisure activities/hobbies [ 28 , 30 , 31 , 36 , 38 , 39 ] and had difficulty travelling [ 26 , 30 , 38 , 41 , 44 ], with some patients reporting that driving was challenging or unsafe [ 33 , 39 , 44 ].

Cancer-related fatigue impacted patients’ ability to engage in self-care [ 16 , 22 , 25 , 26 , 29 , 41 ], and patients felt that they had lost independence because of their fatigue, often relying on others to assist them with daily life [ 22 , 25 , 26 , 33 , 35 ]. Patients also experienced a lack of privacy because of requiring help [ 25 ] and changes in living arrangements [ 41 ] (Table S11).

Sleep

Cancer-related fatigue led to daytime sleepiness, as patients would often need to rest [ 27 , 33 , 37 , 41 – 43 ]. Patients had difficulty initiating sleep/falling asleep [ 16 , 37 , 44 ] and experienced worsening sleep quality/efficiency because of fatigue but also noted that poor/shorter sleep exacerbated their fatigue experiences [ 28 , 29 , 35 ] (Table S12).

Social Functioning and Relationships

Cancer-related fatigue led to difficulty participating in social events or a complete inability to attend, resulting in patients reducing the frequency or length of their attendance and their engagement with others in social settings [ 21 , 22 , 30 , 31 , 39 – 41 , 44 ]. Fatigue impacted patients’ ability to maintain friendships [ 22 , 24 , 29 , 30 , 35 , 40 , 41 ], and patients experienced a lack of understanding from others regarding the impact of fatigue on their day-to-day lives, placing undue pressure on them to rest and/or exercise [ 21 , 23 , 25 , 37 , 41 ].

Cancer-related fatigue impacted the roles or relationships of patients within their families, including a shift from parent/caregiver to requiring care themselves [ 16 , 25 , 29 , 35 , 37 , 39 , 43 , 44 ]. Patients experienced difficulties with their romantic relationships, including complete relationship breakdowns, or with sexual intimacy [ 21 , 25 , 37 , 40 , 41 ] (Table S13).

Work and Financial

Fatigue caused some patients to be completely unable to work [ 22 , 35 , 36 , 39 , 41 , 44 ], which might lead to financial stress, alongside medical bills [ 22 , 41 ]. Others reported a negative impact on their productivity/performance or time working [ 22 , 33 , 35 , 40 , 41 ], or a need to adapt to a work-from-home schedule to accommodate their fatigue [ 41 ]. Consequently, cancer-related fatigue impacted patients’ career/retirement plans, necessitating early retirement in some cases [ 39 , 41 ] (Table S14).

Coping Strategies

Patients coped with their cancer-related fatigue by managing their energy expenditure or planning activities to maximise their capabilities [ 16 , 21 , 22 , 24 , 25 , 27 , 28 , 32 , 38 , 40 , 41 ]. Engaging in activities/hobbies [ 28 – 30 , 41 ], or physical activity and/or exercise, such as walking, helped some patients cope [ 21 , 23 , 27 – 29 , 38 , 41 , 44 ], as did passive activities such as massage or stretching [ 24 ]. Patients adapted their diet to increase their energy levels [ 23 , 24 , 29 , 38 , 39 , 41 ] and utilised herbal and/or alternative therapies, such as dried mugwort and seeking sunlight/warming therapies [ 24 , 29 ].

A range of psychological coping strategies were also reported, including psychological therapies [ 41 ], attempting to fight off the fatigue [ 25 , 29 ], acceptance of fatigue as part of daily life [ 21 , 22 , 25 , 29 , 37 , 41 ], waiting to feel better [ 23 , 25 , 26 , 42 ] or adopting a positive mindset and retaining hope that their condition would improve while acknowledging that they had navigated previous tough instances of fatigue [ 22 , 25 , 29 , 30 , 40 , 41 ]. Less frequently reported psychological coping strategies included relaxation and being outdoors [ 29 ], drawing upon religion/spirituality [ 22 , 29 ], shifting attention away from their fatigue [ 29 ] and their personal fate or ‘ ming ’ [ 29 ]. Patients also turned to their immediate network for both physical and emotional support, including their family or partner, friends, community and HCPs [ 22 , 25 , 26 , 29 , 37 , 40 , 41 ] (Table S15).

Unmet Needs

The most frequently reported unmet treatment need regarding cancer-related fatigue was that patients felt there was a lack of, or inappropriate, support from HCPs, including the perception that HCPs were disinterested [ 21 , 23 , 25 , 41 , 44 ] or did not have adequate time to address their fatigue-related concerns [ 22 , 23 , 44 ]. Some patients requested further information relating to their diagnosis and subsequent treatment [ 23 , 29 , 37 ]. An absence of holistic assessments [ 23 ] and a lack of efficacious treatment to treat cancer-related fatigue was also reported [ 44 ] (Table S16).

Conceptual Model of the Patient Experience of Fatigue in Oncology

Although a combined conceptual model of cancer-related fatigue and pain was identified in soft tissue sarcoma [ 15 ], no existing holistic comprehensive conceptual model depicting the patient experience of cancer-related fatigue across indications was identified by this study. Therefore, a conceptual model of the patient experience of cancer-related fatigue was developed (Fig. 3 ), which provides a visual depiction of fatigue triggers, fatigue descriptors across temporal cancer stages and information on the onset, frequency, duration and severity of fatigue, the impact of fatigue on aspects of patients HRQoL, coping strategies and unmet needs. Fig. 3 Conceptual model of the patient experience of fatigue in oncology. HCP healthcare professional. Concepts were included if reported by > 1 patient, in at least one publication

Discussion

Over 100 unique concepts for the patient experience of cancer-related fatigue were identified and synthesised from 26 primary qualitative studies globally ( N = 512 patients), including a wide range of oncology indications. These concepts were aggregated into fatigue triggers, descriptors, onset, frequency, severity, duration and impact on HRQoL. While cognitive or mental fatigue was described by patients living with cancer or during active treatment, physiological fatigue was reported across all three temporal treatment stages. Comparison of fatigue descriptors suggested that severe fatigue experiences may be more common while living with cancer or during active treatment and post-treatment. Cancer-related fatigue was triggered by oncology treatments, disease-related factors, demographic factors, daily activities and lifestyle factors, meaning that the onset and trajectory of fatigue were often varied and unpredictable between patients. In different publications, fatigue was described as occurring persistently across each day, or as fluctuating with intermittent fatigue episodes. Fatigue also varied in duration across temporal stages, lasting several years in some patients and hours, days, weeks or months in others. While fatigue was commonly described as severe or highly bothersome and, for some patients, was not relieved with rest or treatment, other patients referred to fatigue as tolerable. However, fatigue considerably affected how patients function in their activities of daily living, alongside their physical and social functioning, emotional and physiological wellbeing, sleep, work and finances, emphasising the importance of assessing fatigue-related outcomes in oncology clinical trials, alongside other symptoms and traditional endpoints.

Coping strategies were largely self-developed by patients and included managing their energy expenditure or planning activities to maximise their capabilities, engaging in exercise or walking, turning to their immediate network for both physical and emotional support and following a good diet. Patients reported substantial unmet needs in cancer-related fatigue treatment; there was inappropriate or a lack of support from HCPs, with HCPs appearing to be disinterested or to have inadequate time to address their fatigue-related concerns, and a lack of holistic assessments, efficacious treatment or information relating to their diagnosis and subsequent treatment.

The findings of this review were used to inform the development of a new holistic conceptual model of fatigue in oncology, incorporating patient coping strategies and unmet treatment needs. In a previously published model focusing on pain and fatigue in soft tissue sarcoma, fatigue was conceptualised across eight concepts within three broad domains ("fatigability”, “fatigue symptoms” and “fatigue impact”) [ 15 ]. The current model builds upon the high-level concepts included in this model and broadly aligns with the Assessing Symptoms of Cancer Using Patient-Reported Outcomes (ASCPRO) conceptual model of cancer-related fatigue [ 45 ], where cancer-related fatigue was shown to be influenced by cancer and cancer treatments. Fatigue was described as the subjective experience of weariness, tiredness and low energy, and/or the perceived impact on functioning (e.g. physical, cognitive, emotional and social functioning). In the ASCPRO model, a separate domain highlighted the impact that fatigue and other symptoms of cancer has on functioning (social, mental and physical) and overall HRQoL. This further supports the conclusion that fatigue is a multi-faceted experience for patients across different oncology diagnoses and at different stages in their disease journey.

This holistic conceptual model provides a useful foundation for early phase clinical trial decision making. However, industry guidance should be followed when selecting, developing or modifying PRO measures in pivotal clinical trials to ensure the correct measurement approach is selected for the population of interest [ 46 , 47 ]. Conceptual models can facilitate both the communication of concepts to be assessed and decision making by regulatory reviewers as to whether a proposed COA/PRO fully captures a concept [ 46 ]. As treatments are beginning to extend patient survival, and may be less aggressive, HRQoL-related concepts such as fatigue should be considered for measurement to enable patient-centric treatment development. Identifying or developing appropriate PRO measures to better assess these concepts also has important applications for routine clinical practice and may facilitate improved patient and clinician discussions about fatigue [ 48 ]. Despite the availability of several PRO measures that assess aspects of fatigue in oncology, further research is required to explore which measures are most appropriate for different clinical research scenarios in different contexts, while considering relevant industry guidelines, such as FDA Patient-Focused Drug Development (PFDD) Guidance [ 46 , 49 ].

This targeted literature review informed the development of a novel conceptual model for cancer-related fatigue which, to our knowledge, is the first that is informed by the experiences of a large number of patients across a range of disease stages and oncology indications globally, covering both solid and haematological malignancies. The model provides a holistic overview of the patient experience of fatigue in oncology, alongside patient coping strategies and unmet needs, which confirms the importance of fatigue measurement in a clinical trial setting and may guide the selection of appropriate measurement strategies in future oncology clinical trials. As patient experiences of fatigue are influenced by oncology indication and treatment, some aspects of the conceptual model developed in this review may not be relevant to all patients. Therefore, the application of the model should be tailored to each disease and population to ensure relevance. Furthermore, planning the timing of assessments to detect changes in fatigue is difficult when the symptom fluctuates substantially, and frequent assessments during long oncology trials might increase patient burden. Additionally, further research would be necessary to determine whether the experience of fatigue is comparable across all forms of cancer. Although consideration was given to the varied representation of cancer types and stages when selecting the most relevant publications for inclusion, it is acknowledged that the conceptual model does not capture the patient experience of fatigue regarding other cancer types not identified in the literature review. It is unclear whether other cancer types were not identified because of a lack of research more generally or whether fatigue is not a key component of the patient experience in other cancer types.

Conclusion

This review demonstrated that fatigue is an important, impactful symptom for patients with cancer, who commonly experience unmet treatment needs, including poor support from HCPs, and informed the first conceptual model of cancer-related fatigue across oncology indications, treatments and disease stages. Cancer-related fatigue is a key concept for assessment in oncology clinical trials and further research must be conducted to identify and evaluate how currently used PROs and COAs cover the patient fatigue experience.

Supplementary Information

Below is the link to the electronic supplementary material. Supplementary file1 (PDF 821 KB)

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Medical Writing/Editorial Assistance

The authors received writing support from Eleanor Ward, an employee of Clarivate. Assistance from Clarivate was funded by Sanofi. The journal’s Rapid Service and Open Access Fees were also funded by Sanofi.

Author Contributions

Paul Cordero, Helen Kitchen, Natalie Aldhouse, Cecile Gousset, and Sophie Van Tomme, contributed to the study conception and design. Literature searching and data analysis were performed by Chloe Carmichael, Danielle Burns, Jordan Miller, Harriet Makin, and Natalie Aldhouse. All authors contributed to data interpretation and conceptual model development. The first draft of the manuscript was written by Danielle Burns and Chloe Carmichael, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Funding

This study and preparation of this manuscript, including writing support from Clarivate, were funded by Sanofi R&D (Gentilly, France).

Data Availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

Declarations

Conflict of Interest

This study was funded by Sanofi, and Sophie Van Tomme, Cecile Gousset, and Paul Cordero are employees of Sanofi and may hold stocks. Chloe Carmichael, Jordan Miller, Danielle Burns, Harriet Makin, Helen Kitchen, and Natalie Aldhouse are employees and stockholders of Clarivate, which received funding from Sanofi to conduct the analysis and for writing support. The authors have no other relevant financial or non-financial interests to disclose.

Ethical Approval

This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.

References

1. Al Maqbali M Al Sinani M Al Naamani Z Al Badi K Prevalence of fatigue in patients with cancer: a systematic review and meta-analysis J Pain Symptom Manag 2021 61 1 167 89.e14 10.1016/j.jpainsymman.2020.07.037 32768552 Al Maqbali M, Al Sinani M, Al Naamani Z, Al Badi K. Prevalence of fatigue in patients with cancer: a systematic review and meta-analysis. J Pain Symptom Manag. 2021;61(1):167-89.e14. 10.1016/j.jpainsymman.2020.07.037 32768552

2. Cella D Davis K Breitbart W Curt G Coalition F Cancer-related fatigue: prevalence of proposed diagnostic criteria in a United States sample of cancer survivors J Clin Oncol 2001 19 14 3385 3391 10.1200/JCO.2001.19.14.3385 11454886 Cella D, Davis K, Breitbart W, Curt G, Coalition F. Cancer-related fatigue: prevalence of proposed diagnostic criteria in a United States sample of cancer survivors. J Clin Oncol. 2001;19(14):3385–91. 11454886 10.1200/JCO.2001.19.14.3385

3. Berger AM Mooney K Alvarez-Perez A Breitbart WS Carpenter KM Cella D Cancer-related fatigue, version 22015 J Natl Compr Cancer Netw. 2015 13 8 1012 1039 10.6004/jnccn.2015.0122 PMC5499710 26285247 Berger AM, Mooney K, Alvarez-Perez A, Breitbart WS, Carpenter KM, Cella D, et al. Cancer-related fatigue, version 22015. J Natl Compr Cancer Netw. 2015;13(8):1012–39. 10.6004/jnccn.2015.0122 PMC5499710 26285247

4. National Comprehensive Cancer Network. Cancer-Related Fatigue, Version 1 2025. Available at https://www.nccn.org/professionals/physician_gls/pdf/fatigue.pdf . Accessed Jan 2025.

5. Behringer K Goergen H Müller H Thielen I Brillant C Kreissl S Cancer-related fatigue in patients with and survivors of hodgkin lymphoma: the impact on treatment outcome and social reintegration J Clin Oncol 2016 34 36 4329 4337 10.1200/JCO.2016.67.7450 27998235 Behringer K, Goergen H, Müller H, Thielen I, Brillant C, Kreissl S, et al. Cancer-related fatigue in patients with and survivors of hodgkin lymphoma: the impact on treatment outcome and social reintegration. J Clin Oncol. 2016;34(36):4329–37. 27998235 10.1200/JCO.2016.67.7450

6. Groenvold M Petersen MA Idler E Bjorner JB Fayers PM Mouridsen HT Psychological distress and fatigue predicted recurrence and survival in primary breast cancer patients Breast Cancer Res Treat 2007 105 2 209 219 10.1007/s10549-006-9447-x 17203386 Groenvold M, Petersen MA, Idler E, Bjorner JB, Fayers PM, Mouridsen HT. Psychological distress and fatigue predicted recurrence and survival in primary breast cancer patients. Breast Cancer Res Treat. 2007;105(2):209–19. 17203386 10.1007/s10549-006-9447-x

7. Adam S van de Poll-Franse LV Mols F Ezendam NPM de Hingh I Arndt V 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 8 6 3227 3236 10.1002/cam4.2166 31012272 PMC6558477 Adam S, van de Poll-Franse LV, Mols F, Ezendam NPM, de Hingh I, Arndt V, 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;8(6):3227–36. 31012272 10.1002/cam4.2166 PMC6558477

8. Thong MSY van Noorden CJF Steindorf K Arndt V Cancer-related fatigue: causes and current treatment options Curr Treat Options Oncol 2020 21 2 17 10.1007/s11864-020-0707-5 32025928 PMC8660748 Thong MSY, van Noorden CJF, Steindorf K, Arndt V. Cancer-related fatigue: causes and current treatment options. Curr Treat Options Oncol. 2020;21(2):17. 32025928 10.1007/s11864-020-0707-5 PMC8660748

9. Schmidt ME Bergbold S Hermann S Steindorf K Knowledge, perceptions, and management of cancer-related fatigue: the patients' perspective Support Care Cancer 2021 29 4 2063 2071 32860177 10.1007/s00520-020-05686-5 PMC7892505 Schmidt ME, Bergbold S, Hermann S, Steindorf K. Knowledge, perceptions, and management of cancer-related fatigue: the patients’ perspective. Support Care Cancer. 2021;29(4):2063–71. 32860177 10.1007/s00520-020-05686-5 PMC7892505

10. Roila F Fumi G Ruggeri B Antonuzzo A Ripamonti C Fatigoni S Prevalence, characteristics, and treatment of fatigue in oncological cancer patients in Italy: a cross-sectional study of the Italian Network for Supportive Care in Cancer (NICSO) Support Care Cancer 2019 27 3 1041 1047 30084104 10.1007/s00520-018-4393-9 Roila F, Fumi G, Ruggeri B, Antonuzzo A, Ripamonti C, Fatigoni S, et al. Prevalence, characteristics, and treatment of fatigue in oncological cancer patients in Italy: a cross-sectional study of the Italian Network for Supportive Care in Cancer (NICSO). Support Care Cancer. 2019;27(3):1041–7. 30084104 10.1007/s00520-018-4393-9

11. Spathis A Hatcher H Booth S Gibson F Stone P Abbas L Cancer-related fatigue in adolescents and young adults after cancer treatment: persistent and poorly managed J Adolesc Young Adult Oncol 2017 6 3 489 493 10.1089/jayao.2017.0037 28714766 PMC5649403 Spathis A, Hatcher H, Booth S, Gibson F, Stone P, Abbas L, et al. Cancer-related fatigue in adolescents and young adults after cancer treatment: persistent and poorly managed. J Adolesc Young Adult Oncol. 2017;6(3):489–93. 28714766 10.1089/jayao.2017.0037 PMC5649403

12. Smith TG Troeschel AN Castro KM Arora NK Stein K Lipscomb J Perceptions of patients with breast and colon cancer of the management of cancer-related pain, fatigue, and emotional distress in community oncology J Clin Oncol 2019 37 19 1666 1676 10.1200/JCO.18.01579 31100037 PMC6804889 Smith TG, Troeschel AN, Castro KM, Arora NK, Stein K, Lipscomb J, et al. Perceptions of patients with breast and colon cancer of the management of cancer-related pain, fatigue, and emotional distress in community oncology. J Clin Oncol. 2019;37(19):1666–76. 31100037 10.1200/JCO.18.01579 PMC6804889

13. Brown LF Kroenke K Cancer-related fatigue and its associations with depression and anxiety: a systematic review Psychosomatics 2009 50 5 440 447 10.1016/S0033-3182(09)70835-7 19855028 PMC2902246 Brown LF, Kroenke K. Cancer-related fatigue and its associations with depression and anxiety: a systematic review. Psychosomatics. 2009;50(5):440–7. 19855028 10.1176/appi.psy.50.5.440 PMC2902246

14. Brown DJ McMillan DC Milroy R The correlation between fatigue, physical function, the systemic inflammatory response, and psychological distress in patients with advanced lung cancer Cancer 2005 103 2 377 382 10.1002/cncr.20777 15558809 Brown DJ, McMillan DC, Milroy R. The correlation between fatigue, physical function, the systemic inflammatory response, and psychological distress in patients with advanced lung cancer. Cancer. 2005;103(2):377–82. 15558809 10.1002/cncr.20777

15. Barrett L Elliott E Voorhaar M Ingelgård A Griebsch I Wong B A mixed-methods study to better measure patient-reported pain and fatigue in soft tissue sarcoma Oncol Therapy 2023 11 1 129 143 10.1007/s40487-022-00219-y PMC9935765 36633810 Barrett L, Elliott E, Voorhaar M, Ingelgård A, Griebsch I, Wong B, et al. A mixed-methods study to better measure patient-reported pain and fatigue in soft tissue sarcoma. Oncol Therapy. 2023;11(1):129–43. 10.1007/s40487-022-00219-y PMC9935765 36633810

16. Gries KS Fastenau J Seo C Potrata B Iaconangelo C Serrano D Development of the multiple myeloma symptom and impact questionnaire: a new patient-reported outcome instrument to assess symptom and impacts in patients with multiple myeloma Value Health 2021 24 12 1807 1819 10.1016/j.jval.2021.06.010 34838279 Gries KS, Fastenau J, Seo C, Potrata B, Iaconangelo C, Serrano D. Development of the multiple myeloma symptom and impact questionnaire: a new patient-reported outcome instrument to assess symptom and impacts in patients with multiple myeloma. Value Health. 2021;24(12):1807–19. 34838279 10.1016/j.jval.2021.06.010

17. Critical Appraisal Skills Programme. CASP qualitative checklist. Available online at https://casp-uk.net/images/checklist/documents/CASP-Qualitative-Studies-Checklist/CASP-Qualitative-Checklist-2018_fillable_form.pdf . Last accessed 01-June-2023.

18. Hsieh H-F Shannon SE Three approaches to qualitative content analysis Qual Health Res 2005 15 9 1277 1288 10.1177/1049732305276687 16204405 Hsieh H-F, Shannon SE. Three approaches to qualitative content analysis. Qual Health Res. 2005;15(9):1277–88. 16204405 10.1177/1049732305276687

19. Lincoln YS, Guba EG. Naturalistic inquiry. Sage; 1985.

20. Carmichael C, Collins E, Marshall C, Macey J. Qualitative Content Analysis for Concept Elicitation (CACE) in clinical outcome assessment development. ISPOR Europe; 2023; Copenhagen. 2023.

21. Bootsma TI Schellekens MP van Woezik RA van der Lee ML Slatman J Navigating severe chronic cancer-related fatigue: an interpretative phenomenological analysis Psychol Health 2023 38 4 494 517 10.1080/08870446.2021.1973468 34474619 Bootsma TI, Schellekens MP, van Woezik RA, van der Lee ML, Slatman J. Navigating severe chronic cancer-related fatigue: an interpretative phenomenological analysis. Psychol Health. 2023;38(4):494–517. 34474619 10.1080/08870446.2021.1973468

22. Arizona I Sukartini T Efendi F “I Feel Like a Baby”: a cancer-related fatigue experience based on a male perspective Syst Rev Pharm 2020 11 6 1069 1074 Arizona I, Sukartini T, Efendi F. “I Feel Like a Baby”: a cancer-related fatigue experience based on a male perspective. Syst Rev Pharm. 2020;11(6):1069–74.

23. Charles C Di Meglio A Arnedos M Arvis J Baciarello G Blanchard P QualFatigue study: which factors influence the use of specific interventions for breast cancer survivors with fatigue? A cross-sectional exploratory study Support Care Cancer 2021 29 4827 4834 33547524 10.1007/s00520-021-06040-z Charles C, Di Meglio A, Arnedos M, Arvis J, Baciarello G, Blanchard P, et al. QualFatigue study: which factors influence the use of specific interventions for breast cancer survivors with fatigue? A cross-sectional exploratory study. Support Care Cancer. 2021;29:4827–34. 33547524 10.1007/s00520-021-06040-z

24. Kim S Han J Lee MY Jang MK The experience of cancer-related fatigue, exercise and exercise adherence among women breast cancer survivors: insights from focus group interviews J Clin Nurs 2020 29 5–6 758 769 10.1111/jocn.15114 31769562 Kim S, Han J, Lee MY, Jang MK. The experience of cancer-related fatigue, exercise and exercise adherence among women breast cancer survivors: insights from focus group interviews. J Clin Nurs. 2020;29(5–6):758–69. 31769562 10.1111/jocn.15114

25. Levkovich I Cohen M Karkabi K The experience of fatigue in breast cancer patients 1–12 month post-chemotherapy: a qualitative study Behav Med 2019 45 1 7 18 10.1080/08964289.2017.1399100 29095129 Levkovich I, Cohen M, Karkabi K. The experience of fatigue in breast cancer patients 1–12 month post-chemotherapy: a qualitative study. Behav Med. 2019;45(1):7–18. 29095129 10.1080/08964289.2017.1399100

26. Li H Ng MSN Jin X Wong CL ‘Life became slow down’: a descriptive qualitative study of the experiences of cancer-related fatigue amongst people with advanced lung cancer Palliat Med 2023 37 8 1168 1182 10.1177/02692163231184926 37395316 Li H, Ng MSN, Jin X, Wong CL. ‘Life became slow down’: a descriptive qualitative study of the experiences of cancer-related fatigue amongst people with advanced lung cancer. Palliat Med. 2023;37(8):1168–82. 37395316 10.1177/02692163231184926

27. Mikkelsen MK Nielsen DL Vinther A Lund CM Jarden M Attitudes towards physical activity and exercise in older patients with advanced cancer during oncological treatment—a qualitative interview study Eur J Oncol Nurs 2019 41 16 23 10.1016/j.ejon.2019.04.005 31358249 Mikkelsen MK, Nielsen DL, Vinther A, Lund CM, Jarden M. Attitudes towards physical activity and exercise in older patients with advanced cancer during oncological treatment—a qualitative interview study. Eur J Oncol Nurs. 2019;41:16–23. 31358249 10.1016/j.ejon.2019.04.005

28. Homkes DL. The lived experience of lung cancer patients with psychological health and physical activity. Walden University; 2023.

29. Dong X Peng J Li X Zhao Q Xiuwei Z Home coping strategies for fatigue used by patients with lung cancer receiving chemotherapy in rural China: a qualitative study J Nurs Res 2021 29 6 e178 10.1097/jnr.0000000000000453 34483303 Dong X, Peng J, Li X, Zhao Q, Xiuwei Z. Home coping strategies for fatigue used by patients with lung cancer receiving chemotherapy in rural China: a qualitative study. J Nurs Res. 2021;29(6): e178. 34483303 10.1097/jnr.0000000000000453

30. Milne D Hyatt A Billett A Gough K Krishnasamy M Exploring the experiences of people treated with immunotherapies for advanced melanoma and those caring for them: “real-world” data Cancer Nurs 2020 43 2 E97 E104 10.1097/NCC.0000000000000683 30801266 Milne D, Hyatt A, Billett A, Gough K, Krishnasamy M. Exploring the experiences of people treated with immunotherapies for advanced melanoma and those caring for them: “real-world” data. Cancer Nurs. 2020;43(2):E97–104. 30801266 10.1097/NCC.0000000000000683

31. Konidaris G Rofail D Randall J LaFontaine PR Chen C-I Bury D Qualitative patient interviews to characterize the human burden of advanced basal cell carcinoma following Hedgehog pathway inhibitor treatment Dermatol Therapy 2023 13 1747 1761 10.1007/s13555-023-00945-9 PMC10366056 37330458 Konidaris G, Rofail D, Randall J, LaFontaine PR, Chen C-I, Bury D, et al. Qualitative patient interviews to characterize the human burden of advanced basal cell carcinoma following Hedgehog pathway inhibitor treatment. Dermatol Therapy. 2023;13:1747–61. 10.1007/s13555-023-00945-9 PMC10366056 37330458

32. Dolgoy ND O'Krafka P McNeely ML Cancer-related fatigue in head and neck cancer survivors: energy and functional impacts Cancer Treat Res Commun 2020 25 100244 33254042 10.1016/j.ctarc.2020.100244 Dolgoy ND, O’Krafka P, McNeely ML. Cancer-related fatigue in head and neck cancer survivors: energy and functional impacts. Cancer Treat Res Commun. 2020;25: 100244. 33254042 10.1016/j.ctarc.2020.100244

33. Guillemin I Darpelly M Wong B Ingelgård A Griebsch I Development of a disease conceptual model of patient experience with metastatic colorectal cancer: identification of the most salient symptoms and impacts J Cancer Surviv 2024 18 761 771 10.1007/s11764-022-01279-9 36515691 PMC9748881 Guillemin I, Darpelly M, Wong B, Ingelgård A, Griebsch I. Development of a disease conceptual model of patient experience with metastatic colorectal cancer: identification of the most salient symptoms and impacts. J Cancer Surviv. 2024;18:761–71. 36515691 10.1007/s11764-022-01279-9 PMC9748881

34. Cancer Support Community. Cancer cachexia: voice of the patient report. 2021 [updated 2021; cited]. Available from: https://www.cancersupportcommunity.org/sites/default/files/file/2022-10/CCommSupport_Cachexia_Report_Final.pdf .

35. Eek D Blowfield M Krogh C Chung H Eyre TA Development of a conceptual model of chronic lymphocytic leukemia to better understand the patient experience Patient-Patient-Cent Outcomes Res 2021 14 75 87 10.1007/s40271-020-00440-9 PMC7794108 32808103 Eek D, Blowfield M, Krogh C, Chung H, Eyre TA. Development of a conceptual model of chronic lymphocytic leukemia to better understand the patient experience. Patient-Patient-Cent Outcomes Res. 2021;14:75–87. 10.1007/s40271-020-00440-9 PMC7794108 32808103

36. Gable J Ayer D Girvan A Bowman L Abada P Ervin C PCN366-qualitative patient interviews to support the FACT Hepatobiliary Symptom Index-8 among patients with hepatocellular carcinoma and elevated baseline alpha-fetoprotein Value Health 2018 21 S76 10.1016/j.jval.2018.09.448 Gable J, Ayer D, Girvan A, Bowman L, Abada P, Ervin C, et al. PCN366-qualitative patient interviews to support the FACT Hepatobiliary Symptom Index-8 among patients with hepatocellular carcinoma and elevated baseline alpha-fetoprotein. Value Health. 2018;21:S76.

37. Poort H Meade CD Knoop H Gielissen MF Pinilla-Ibarz J Jacobsen PB Adapting an evidence-based intervention to address targeted therapy-related fatigue in chronic myeloid leukemia patients Cancer Nurs 2018 41 1 E28 10.1097/NCC.0000000000000446 27832018 PMC5422141 Poort H, Meade CD, Knoop H, Gielissen MF, Pinilla-Ibarz J, Jacobsen PB. Adapting an evidence-based intervention to address targeted therapy-related fatigue in chronic myeloid leukemia patients. Cancer Nurs. 2018;41(1):E28. 27832018 10.1097/NCC.0000000000000446 PMC5422141

38. Tang CC Draucker C Tejani M Von Ah D Symptom experiences in patients with advanced pancreatic cancer as reported during healthcare encounters Eur J Cancer Care 2018 27 3 e12838 10.1111/ecc.12838 29600524 Tang CC, Draucker C, Tejani M, Von Ah D. Symptom experiences in patients with advanced pancreatic cancer as reported during healthcare encounters. Eur J Cancer Care. 2018;27(3): e12838. 10.1111/ecc.12838 29600524

39. Trudeau JJ He J Rose E Panter C Randhawa S Gater A Content validity of patient-reported outcomes for use in lower-risk myelodysplastic syndromes J Patient-Rep Outcomes 2020 4 1 13 10.1186/s41687-020-00235-4 PMC7450032 32851569 Trudeau JJ, He J, Rose E, Panter C, Randhawa S, Gater A. Content validity of patient-reported outcomes for use in lower-risk myelodysplastic syndromes. J Patient-Rep Outcomes. 2020;4:1–13. 10.1186/s41687-020-00235-4 PMC7450032 32851569

40. Stuhlfauth S Melby L Hellesø R Everyday life after colon cancer: the visible and invisible challenges Cancer Nurs 2018 41 6 E48 E57 10.1097/NCC.0000000000000506 28537958 Stuhlfauth S, Melby L, Hellesø R. Everyday life after colon cancer: the visible and invisible challenges. Cancer Nurs. 2018;41(6):E48–57. 28537958 10.1097/NCC.0000000000000506

41. Bradford A Young K Whitechurch A Burbury K Pearson EJM Disabled, invisible and dismissed—the lived experience of fatigue in people with myeloproliferative neoplasms Cancer Rep 2023 6 1 e1655 10.1002/cnr2.1655 PMC9875604 35705529 Bradford A, Young K, Whitechurch A, Burbury K, Pearson EJM. Disabled, invisible and dismissed—the lived experience of fatigue in people with myeloproliferative neoplasms. Cancer Rep. 2023;6(1): e1655. 10.1002/cnr2.1655 PMC9875604 35705529

42. Parthipan M Feng G Toledano N Donison V Breunis H Sudharshan A Symptom experiences of older adults during treatment for metastatic prostate cancer: a qualitative investigation J Geriatr Oncol 2023 14 1 101397 10.1016/j.jgo.2022.10.012 36988104 Parthipan M, Feng G, Toledano N, Donison V, Breunis H, Sudharshan A, et al. Symptom experiences of older adults during treatment for metastatic prostate cancer: a qualitative investigation. J Geriatr Oncol. 2023;14(1): 101397. 36988104 10.1016/j.jgo.2022.10.012

43. Cheung WY White MK Bayliss MS Stroupe A Lovley A King-Kallimanis BL Patient-reported treatment-related symptom burden for patients with advanced melanoma in Canada Support Care Cancer 2019 27 219 227 29934684 10.1007/s00520-018-4316-9 PMC6281076 Cheung WY, White MK, Bayliss MS, Stroupe A, Lovley A, King-Kallimanis BL, et al. Patient-reported treatment-related symptom burden for patients with advanced melanoma in Canada. Support Care Cancer. 2019;27:219–27. 29934684 10.1007/s00520-018-4316-9 PMC6281076

44. Iguchi T Nakamura Y Akiyama T Chand K Yu E Descriptive study on burden and communication of fatigue among castration-resistant prostate cancer patients in Japan Curr Med Res Opin 2022 38 3 417 426 10.1080/03007995.2021.2006534 34918590 Iguchi T, Nakamura Y, Akiyama T, Chand K, Yu E. Descriptive study on burden and communication of fatigue among castration-resistant prostate cancer patients in Japan. Curr Med Res Opin. 2022;38(3):417–26. 34918590 10.1080/03007995.2021.2006534

45. Barsevick AM Cleeland CS Manning DC O'Mara AM Reeve BB Scott JA ASCPRO recommendations for the assessment of fatigue as an outcome in clinical trials J Pain Symptom Manag 2010 39 6 1086 1099 10.1016/j.jpainsymman.2010.02.006 PMC2909842 20538190 Barsevick AM, Cleeland CS, Manning DC, O’Mara AM, Reeve BB, Scott JA, et al. ASCPRO recommendations for the assessment of fatigue as an outcome in clinical trials. J Pain Symptom Manag. 2010;39(6):1086–99. 10.1016/j.jpainsymman.2010.02.006 PMC2909842 20538190

46. Food and Drug Administration (FDA). Patient-focused drug development: selecting, developing, or modifying fit-for-purpose clinical outcome assessments. Guidance for Industry, food and drug administration staff, and other stakeholders. Draft guidance. 2022.

47. Food and Drug Administration (FDA). Guidance for industry patient-reported outcome measures: use in medical product development to support labeling claims. 2009. 10.1186/1477-7525-4-79 PMC1629006 17034633

48. Snyder CF Aaronson NK Choucair AK Elliott TE Greenhalgh J Halyard MY Implementing patient-reported outcomes assessment in clinical practice: a review of the options and considerations Qual Life Res 2012 21 1305 1314 10.1007/s11136-011-0054-x 22048932 Snyder CF, Aaronson NK, Choucair AK, Elliott TE, Greenhalgh J, Halyard MY, et al. Implementing patient-reported outcomes assessment in clinical practice: a review of the options and considerations. Qual Life Res. 2012;21:1305–14. 22048932 10.1007/s11136-011-0054-x

49. Food and Drug Administration (FDA). Patient-focused drug development: incorporating clinical outcome assessments into endpoints for regulatory decision-making. guidance for industry, food and drug administration staff, and other stakeholders. Draft guidance. 2023.