Two investigators (PJL and QW) conducted a systematic search in the WoSCC database, covering the period from January 1st, 2001 to May 18th, 2023. In cases of disagreement, a third reviewer (ZGD) provided the final decision. The search queries used were TS = (cancer-related fatigue), and the publication date range was set from 2001-01-01 to 2023-05-18. The search was limited to the Social Sciences Citation Index (SSCI) and Science Citation Index Expanded (SCI-EXPANDED) editions. Only reviews and articles written in English were considered, while other article types such as conference abstracts and editorials were excluded. This study was performed based on the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines (7) ( Supplementary Table 1 ). The systematic search yielded 3,154 records, and 2,566 studies were included in the final analysis ( Figure 1 ). All relevant publications were downloaded on May 18th, 2023. The results were stored in download_results.txt format, and the content included “full record and cited references.”

All data were imported into CiteSpace 6.2.R3 and duplicate entries were eliminated. The publication year was analyzed using WoSCC. The collaboration among authors, institutions, and countries, as well as the co-citation of references and journals, and the co-occurrence of keywords were visualized. The R package “bibliometrix” (8) was employed to analyze the geographical distribution of countries. The findings were presented in figures and tables using techniques such as time slicing, thresholding, and pruning. We set the time span as 2001.01–2023.12 and the years per slice as 1, and chose the suitable pruning methods (minimum spanning tree, pathfinder, or no) according to the analysis results. The size of nodes in the various network maps was indicative of the frequency of co-occurrence or co-citation, while the color denoted the year. The citation bursts of references and keywords were analyzed to find the emerging themes in the CRF field. In the journal co-citation analysis, we merged the same journals (“cancer” and “cancer-am cancer soc”) to an alias list. The synonyms in keyword analysis were also merged, including “cancer-related fatigue” and “cancer related fatigue,” “cancer survivors” and “survivors,” etc.

2566 articles and review articles pertaining to CRF were published from January 2001 to May 2023. As depicted in Figure 2 , there has been a stable growth trend in the number of annual publications and citations since 2001, as heightened interests among scholars in this domain. Notably, the most number of publications reached 271 in 2021 and 2022, and the highest increasing number reached 82 from 2019 to 2020. The citations ranged from 69 in 2002 to a substantial 11,731 in 2022, reflecting increasing attention to the CRF field.

A total of 10,649 authors published studies about CRF according to CiteSpace. Eduardo Bruera published the most articles (n = 35), followed by Christine Miaskowski (n = 30), Leorey N Saligan (n = 29), Sriram Yennurajalingam (n = 25), and Julienne E Bower (n = 23) ( Table 1 ). However, the density of author collaboration was relatively low, reflecting that scholars need to enhance further cooperation in this field. The network map outlines the potential collaboration among authors, including 10,170 connections ( Figure 3A ). Some authors have exhibited close collaborative relationships, such as Julienne E Bower and Patricia A Ganz. The degree of centrality can help us identify hubs in the map, and Paul B Jacobsen has the highest centrality (= 0.04), showing a lack of close cooperation.

A co-citation relationship was established among the authors when they were cited simultaneously in one or more articles. The core authors can be shown intuitively through the network map ( Figure 3B ). CiteSpace identified 1,007 co-cited authors, with 25 of them being co-cited over 200 times and 66 being co-cited no less than 100 times. The most co-cited authors were Julienne E Bower (897 co-citations), Ann M Berger (582 co-citations), David Cella (520 co-citations), Ollie Minton (360 co-citations), and G A Curt (355 co-citations) ( Table 1 ).

From 2001 to the present, 1,041 institutions from 70 countries had published studies about CRF. The top 5 productive institutions were the University of Texas System (178, 2.77%), UTMD Anderson Cancer Center (159, 2.48%), University of California System (141, 2.19%), Research Libraries UK (131, 2.04%), and Harvard University (84, 1.31%), four of which were from the USA ( Table 2 ). Research Libraries UK exhibited the highest centrality (= 0.36). As can be seen from the pruning network map of co-institution ( Figure 4A ), the collaboration among some institutions is relatively close, such as Anderson Cancer Center and University of Texas System, as well as Research Libraries UK and Harvard University.

The United States (1065, 31.26%) had the largest number of publications on CRF, followed by China (314, 9.22%), Germany (206, 6.05%), England (193, 5.66%), and Canada (186, 5.46%) ( Supplementary Table 2 ). 70 nodes and 471 connections made up the network map of countries co-occurrence with a density of 0.195 ( Figure 4B ). The USA serves as a pivotal intermediary in the CRF area, exemplifying substantial contributions to the CRF area and assuming the central roles. Figure 5 visually represents the global distribution of publications, highlighting the cooperation among countries.

650 journals were identified through WoSCC. Supportive Care in Cancer published the most studies (212, 8.26%), followed by Journal of Pain and Symptom Management (116, 4.52%), Cancer (71, 2.77%), Cancer Nursing (62, 2.42%), and Integrative cancer therapies (58, 2.26%) ( Table 3 ). Of the top 10 journals publishing the most articles in the CRF field, Cancer had the highest impact factor (IF) of 6.16, while no journals with an IF > 10 were observed.

We analyzed the co-cited journals with k = 5 from time slicing of 1 year, and 286 co-cited journals were identified. The co-citations of six journals were more than 1,000, and 20 journals were more than 500. The most co-cited journals were the Journal of Clinical Oncology (1900, 4.41%), Cancer (1806, 4.19%), Supportive Care in Cancer (1674, 3.89%), Journal of Pain and Symptom Management (1562, 3.63%), Annals of Oncology (1080, 2.51%), and Oncology Nursing Forum (1025, 2.38%) ( Supplementary Table 2 ). Of these, Annals of Oncology had the highest IF (= 50.45), followed by the Journal of Clinical Oncology (IF = 45.27). 286 nodes and 2,324 connections made up the network map of countries co-occurrence with a density of 0.057 ( Figure 6 ). Supportive Care in Cancer had the highest centrality (= 0.11), followed by PLOS ONE (= 0.09), Psycho-oncology (= 0.07), Medicine & Science in Sports & Exercise (= 0.07), and Integrative cancer therapies (= 0.07).

The dual-map overlay of the journals revealed the relationship distribution of subject categories among the journals ( Figure 7 ). Three predominant citation paths colored with green were identified, which means that the studies published in the Medicine/Medical/Clinical journals were mainly cited by those published in the Molecular/Biology/Genetics (z = 4.39, f = 11,470), Health/Nursing/Medicine (z = 7.10, f = 18,100), and Psychology/Education/Social journals (z = 2.43, f = 6,698).

When the documents were cited simultaneously, a co-citation relationship was established among them. We analyzed the most co-cited references (k = 25) with a time slicing of 1 year. The core references can be displayed visually through the network map ( Figure 8 ), containing 6,980 links with a density of 0.0076. Of 1,360 co-cited references identified through CiteSpace, 13 were co-cited no less than 50 times, and 117 were co-cited no less than 20 times. Table 4 displays the top 10 co-cited references. “Comparison of Pharmaceutical, Psychological, and Exercise Treatments for Cancer-Related Fatigue: A Meta-analysis”, authored by Mustian KM et al. and published in JAMA Oncology was the most co-cited document in the CRF area, which indicated that exercise and psychological treatments were more effective than pharmaceutical interventions for CRF through meta-analyses (9). Berger AM et al. provided recommendations for screening and treatments of CRF (10). Bower JE et al. summarized the possible mechanisms, risk factors, and treatments for CRF (4). Campbell KL et al. provided a consensus statement about exercise recommendations for cancer survivors (11). Hilfiker R et al. (12) evaluated the effects of non-pharmaceutical interventions on CRF. Overall, 6 of the top 10 most co-cited documents were reviews, and 4 were guidelines.

Figure 9 displays the top 25 documents with the strongest citation bursts, showing growing interest in the emerging field. The earliest beginning year of citation burst of reference was from 2002 to 2005 (strength = 19.63), entitled “Impact of Cancer-Related Fatigue on the Lives of Patients: New Findings From the Fatigue Coalition” (18) by Curt GA et al. and published in Oncologist. “Comparison of Pharmaceutical, Psychological, and Exercise Treatments for Cancer-Related Fatigue: A Meta-analysis” (9) published by Mustian KM et al. had the strongest strength of 50.32, which was also the most co-cited reference.

Keywords represent a high generalization of the central theme of an article. Analyzing keywords can help to identify the research hot spots in the CRF field over a period of time. We analyzed the top 50 highest-frequency keywords in each time slice. 565 nodes and 4,178 connections made up the network map of keywords co-occurrence with a density of 0.0262 ( Figure 10 ). Of 565 keywords identified through CiteSpace, 31 appeared over 100 times, and 111 appeared no less than 10 times. Supplementary Table 3 presents the top 20 keywords in CRF research. The main contents of the CRF field were identified as “Quality of life” (1315), “breast cancer” (841), “survivors” (614), “management” (564), “chemotherapy” (471), “physical activity” (370), and “depression” (355). 10 clusters were revealed in the cluster analysis of keywords through CiteSpace ( Figure 10 ), including survivorship, assessment, yoga, proinflammatory cytokines, validation, cognitive impairment, inflammation, anemia, exercise, hypoxia, and chemotherapy.

Figure 11 displays the top 50 keywords with the strongest citation bursts, which elucidates the evolving patterns of focal points in the CRF area. Notably, the keyword “epoetin alpha” was the strongest burst (strength = 26.78) and also has the earliest year of citation bursts (2001). The keywords “risk factors,” “systematic review,” “acupuncture,” “anxiety,” and “traditional Chinese medicine” appeared in 2019, while “guidelines” occurred in 2021, which were the most recent citation bursts. Moreover, “insomnia,” “colorectal cancer,” “risk factors,” “systematic review,” and “guidelines” have continued to be of ongoing interest until the year 2023.

This study conducted bibliometric and visualization analyses using CiteSpace to examine 2,566 scientific articles published between 2001 and 2023, providing comprehensive knowledge network maps of CRF. The findings indicate that CRF has garnered extensive attention since 2001, with a notable surge in interest observed in 2019, showing sustained attention towards CRF over the coming years. The most prolific author is Eduardo Bruera from the UTMD Anderson Cancer Center, and the most co-cited author is Julienne E Bower from the University of California. Additionally, the University of Texas System is the most productive institution. Nine countries (the USA, Germany, England, Canada, Netherlands, Italy, France, Japan, and Greece) have embarked on comprehensive research on CRF since 2001. Here in this article the United States and China made the most contributions to this field. However, the low centrality of China highlights the need for Chinese scholars to enhance international association and collaboration.

Supportive Care in Cancer published the most studies on CRF, while Journal of Clinical Oncology has the highest number of co-citations. Most-cited references generally address the possible mechanisms and treatments of CRF. The top ten keywords with the highest frequency of occurrence are quality of life, cancer-related fatigue, breast cancer, survivors, management, chemotherapy, randomized controlled trial, fatigue, physical activity, and depression. Our analysis of keywords with the strongest citation bursts have revealed that “yoga,” “inflammation,” “hypoxia,” “anemia,” “exercise,” “acupuncture,” “anxiety,” “traditional Chinese medicine,” and “insomnia” might be emerging hotspots in the CRF area.

We summarized the hotspots in CRF research based on the results obtained from CiteSpace, primarily encompassing risk factors (anemia, insomnia, depression, and anxiety), treatments (exercise, yoga, acupuncture, and traditional Chinese medicine), and mechanisms (inflammation and hypoxia) of CRF.

The results of this analysis indicate that recent research on the risk factors for CRF has predominantly been focused on insomnia, anxiety, and depression. Anemia remains a risk factor for CRF, and erythropoietin is recommended for patients with CRF and concomitant anemia (1). The main potential mechanisms by which insomnia, anxiety, and depression cause CRF include inflammation, HPA axis dysregulation, neurotransmitter alterations, and disturbances in circadian rhythms. Analysis of the keywords with the strongest citation bursts highlights inflammation as current hotspot in research on the mechanisms underlying the development of CRF. Inflammation is closely associated with HPA axis dysfunction, alterations in neurotransmitters, disruptions in circadian rhythms, and skeletal muscle and mitochondrial dysfunction, all of which collectively exert a synergistic effect on the onset and progression of CRF. Several studies have indicated that modulating the levels of pro-inflammatory cytokines, such as IL-1RA, IL-6, and TNF-α, to ameliorate systemic and neural inflammation can effectively alleviate CRF (79–81).

Cluster analysis of keywords indicated that hypoxia is a potential mechanism underlying the development of CRF, possibly representing an emerging topic for future studies in the field of CRF research. HIF-related pathways are activated in hypoxic conditions, which can modulate the functions of immune cells, release of inflammatory cytokines, oxidative stress status, and mitochondrial function. Targeting HIF-related pathways has been proven to be a possible therapeutic strategy for various chronic inflammatory and neurodegenerative diseases (115) and may potentially aid the improvement of CRF (55, 104). However, further substantiation through more evidence is warranted to determine whether targeting HIF-related pathways can ameliorate CRF.

The findings of this study highlight the current research hotspots regarding the risk factors, treatments, and mechanisms of CRF, and provide novel insights into future therapeutic directions for CRF. Notably, the results of this study indicated that hypoxia, which is closely associated with inflammation, is one of the less explored mechanisms underlying the development of CRF. Further studies are needed to clarify whether hypoxia-associated pathways can be crucial targets in the treatment of CRF.

Treatment strategies for CRF have been evaluated in previous studies. According to existing guidelines, exercise is the most effective intervention for improving CRF. However, there is no consensus on the optimal type, frequency, and intensity of exercise suitable for various types and stages of cancer. Future in-depth studies on this topic are needed to aid clinicians in designing optimal treatment strategies for patients with CRF. Acupuncture has demonstrated significant efficacy in ameliorating cancer-related symptoms. However, future extensive, large-scale, clinical studies are needed to verify its potential in improving CRF.

This study has some limitations. First, we only retrieved English literature related to CRF from the SSCI and SCI-Expanded databases through the WoSCC. Unpublished articles and articles published in other languages were not included. Second, the literature search was limited to articles with “cancer-related fatigue” in their titles, abstracts, or keywords, potentially leading to the data being insufficiently comprehensive.